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Acupuncture for functional dyspepsia: Study protocol for a two-center, randomized controlled trial

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Functional dyspepsia (FD) is a common health problem currently without any optimal treatments. Acupuncture has been traditionally sought as a treatment for FD. The aim of this study is to investigate whether acupuncture treatment helps improve symptoms of FD.Methods/design: A two-center, randomized, waitlist-controlled trial will be carried out to evaluate whether acupuncture treatment improves FD symptoms. Seventy six participants aged 18 to 75 years with FD as diagnosed by Rome III criteria will be recruited from August 2013 to January 2014 at two Korean hospitals. They will be randomly allocated either into eight sessions of partially individualized acupuncture treatment over 4 weeks or a waitlist group. The acupuncture group will then be followed-up for 3 weeks with six telephone visits and a final visit will be paid at 8 weeks. The waitlist group will receive the identical acupuncture treatment after a 4-week waiting period. The primary outcome is the proportion of responders with adequate symptom relief and the secondary outcomes include Nepean dyspepsia index, EQ-5D, FD-related quality of life, Beck's depression inventory, state-trait anxiety inventory questionnaire, and level of ghrelin hormone. The protocol was approved by the participating centers' Institutional Review Boards. Results of this trial will help clarify not only whether the acupuncture treatment is beneficial for symptom improvement in FD patients but also to elucidate the related mechanisms of how acupuncture might work.Trial registration: ClinicalTrials.gov Identifier: NCT01921504.
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S T U D Y P R O T O C O L Open Access
Acupuncture for functional dyspepsia: study
protocol for a two-center, randomized controlled
trial
Gajin Han
1
, Seok-Jae Ko
1
, Jae-Woo Park
1
, Jinsung Kim
1
, Inkwon Yeo
2
, Hyejung Lee
3
, Song-Yi Kim
3
and Hyangsook Lee
3*
Abstract
Background: Functional dyspepsia (FD) is a common health problem currently without any optimal treatments.
Acupuncture has been traditionally sought as a treatment for FD. The aim of this study is to investigate whether
acupuncture treatment helps improve symptoms of FD.
Methods/design: A two-center, randomized, waitlist-controlled trial will be carried out to evaluate whether acupuncture
treatment improves FD symptoms. Seventy six participants aged 18 to 75 years with FD as diagnosed by Rome III criteria
will be recruited from August 2013 to January 2014 at two Korean Medicine hospitals. They will be randomly allocated
either into eight sessions of partially individualized acupuncture treatment over 4 weeks or a waitlist group. The
acupuncture group will then be followed-up for 3 weeks with six telephone visits and a final visit will be paid at 8 weeks.
The waitlist group will receive the identical acupuncture treatment after a 4-week waiting period. The primary outcome is
the proportion of responders with adequate symptom relief and the secondary outcomes include Nepean dyspepsia
index, EQ-5D, FD-related quality of life, Becks depression inventory, state-trait anxiety inventory questionnaire, and level of
ghrelin hormone. The protocol was approved by the participating centersInstitutional Review Boards.
Discussion: Results of this trial will help clarify not only whether the acupuncture treatment is beneficial for symptom
improvement in FD patients but also to elucidate the related mechanisms of how acupuncture might work.
Trial registration: ClinicalTrials.gov Identifier: NCT01921504.
Keywords: Acupuncture, Functional dyspepsia, Ghrelin, Randomized controlled trial, Waitlist
Background
Functional dyspepsia (FD) is a functional gastrointestinal
disorder without any structural lesion [1]. It is reported that
the prevalence of FD ranges from 8% to 23% in Asia [2],
and in particular, FD is claimed to affect 25% of the South
Korean population [3]. Though FD is not a life-threatening
disease, FD patients suffer from a poor quality of life (QoL),
which is regarded as an economic burden on society [4].
Although various treatments for FD, such as proton pump
inhibitors, prokinetic agents, tricyclic antidepressants,
and antinociceptive agents are available [5-9], many
FD patients turn to other complementary and alterna-
tive therapies largely due to a lack of satisfactory relief
by these treatments [10].
Acupuncture treatment is one of the most sought-after
therapeutic modalities in complementary and alternative
medicine. It has been frequently used to treat symptoms
of FD [11] largely based on the following rationales:
firstly, acupuncture is well known to relieve pain in vari-
ous conditions [12] and may help reduce epigastric pain
or burning sensation [4]; secondly, previous studies have
shown that manual acupuncture and electro-acupuncture
modulates gastric/duodenal motility through the activation
of sympathetic efferent nerve fibers or vagal nerve fibers
[13]; finally, since patients with FD have been reported to
have higher levels of psychological distress or depression
than healthy subjects [14,15], the anxiolytic or antidepressant
* Correspondence: erc633@khu.ac.kr
3
Acupuncture and Meridian Science Research Center, College of Korean
Medicine, Kyung Hee University, Kyung Hee dae-ro 26, Dongdaemun-gu,
Seoul 130-701, South Korea
Full list of author information is available at the end of the article
TRIALS
© 2014 Han et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Han et al. Trials 2014, 15:89
http://www.trialsjournal.com/content/15/1/89
effects of acupuncture have been utilized to minimize wors-
ening of FD symptoms [16-18].
However, previous studies have reported inconsistent
findings of the clinical benefit of acupuncture treatment
for FD [4,19]. Nevertheless, these studies have been criti-
cized for adopting relatively sub-optimal acupuncture
treatment, i.e., three times a week for 2 weeks [19,20], or
testing a less generalizable treatment regimen, i.e., daily
acupuncture treatment for 4 weeks [4]. According to a
systematic review by Zhu [21], the acupuncture treat-
ment for FD lacks high-quality evidence. Hence, it was
addressed that randomized clinical trials corresponding
with the CONSORT statement and STandards for Reporting
Interventions in Clinical Trials of Acupuncture (STRICTA)
recommendations have to be implemented to evaluate the
efficacy of acupuncture for FD. In addition, considering the
questions which have been raised so far on the adequacy of
various sham acupuncture controls [22,23], care should be
taken before simply adopting any available sham devices or
procedures in the early phase.
Given that FD is now regarded as a complex disorder
of which the pathophysiological mechanisms are incon-
clusive [24], various factors are likely to come into play.
Among them, ghrelin, an orexigenic peptide, has been
shown to play an important role in gastric motility, food
intake, and potential gastroprotection against acute gas-
tric mucosal injury [25,26]. However, it is yet to be stud-
ied whether ghrelin is associated with the mechanisms
of acupuncture treatment in patients with FD [27,28].
Taken together, we felt the need to properly test
whether acupuncture treatment would help symptom
improvement in FD patients and, subsequently, the re-
lated mechanism. Therefore, we propose a two-center,
randomized, waitlist-controlled trial investigating the ef-
fectiveness of acupuncture for symptom improvement in
patients with FD and to assess whether the change in
ghrelin secretion is associated with acupuncture treatment.
Methods/design
Objectives
The aims of this study are to: i) assess the effect of acu-
puncture treatment on patients with FD in comparison
with waitlist group with respect to adequate symptom
relief and ii) to elucidate whether ghrelin level is associ-
ated with clinical effect of acupuncture.
Hypothesis
We hypothesize that eight sessions of acupuncture treat-
ment over 4 weeks will improve symptoms of FD.
Design
A two-center, randomized, waitlist-controlled trial will be
conducted at the Kyung Hee University Korean Medicine
Hospital and Kyung Hee University Hospital at Gangdong
in Seoul, Korea from August 2013 to January 2014. The
flow of the entire trial is shown in Figure 1.
Inclusion and exclusion criteria
Inclusion criteria
Participants who meet the following criteria will be included:
i) Individuals between the ages of 18 and 75 years, able
to read and write Korean language
ii) Individuals who meet the Rome III FD criteria
iii)Individuals who check more than four points on the
visual analogue scale (VAS; 0, no symptom disturbance
at all; 10, very severe) for dyspeptic symptoms
iv) Individuals who have normal
esophagogastroduodenoscopy results within a year
and have been diagnosed with FD by a specialist
consultation
v) Individuals who receive no other treatments during
the study
vi) Individuals who voluntarily agree with a study
protocol and sign a written informed consent
Exclusion criteria
Participants who report any of the following will be
excluded:
i) Individuals who have peptic ulcer or
gastroesophageal reflux disease confirmed by
esophagogastroduodenoscopy
ii) Individuals who have obvious signs of irritable bowel
syndrome
Random allocation (N = 76)
&
baseline measurement
Follow-up assessment
Recruitment
(Screening, Eligibility, and Exclusions)
Waitlist group
(n = 38)
Waiting
for 4 weeks
(6 telephone visits)
Acupuncture group
(n = 38)
Acupuncture
treatment
for 4 weeks
Follow-up
for 4 weeks
(6 telephone visits)
Acupuncture
treatment
for 4 weeks
Primary outcome assessment
4 weeks
}
4 weeks
}
1 week
}
Figure 1 Flow of the study.
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iii)Individuals who have alarm symptoms (weight loss,
black or tar stool, or dysphagia)
iv) Individuals who have serious structural disease
(disease of heart, lung, liver or kidney) or mental
illness
v) Individuals who have had surgery related with the
gastrointestinal tract, except for appendectomy more
than six months ago
vi) Individuals who are pregnant or breastfeeding
vii)Individuals who are taking drugs which might affect
the gastrointestinal tract; a minimum wash-out
period of two weeks is required before participating
in the trial
viii) Individuals who are HIV-positive
ix) Individuals who have a problem of malabsorption or
maldigestion
x) Individuals who have difficulties in attending the
trial (e.g., paralysis, serious mental illness, dementia,
drug addiction, time constraint, severe disorder in
vision or hearing, illiteracy)
xi) Individuals unwilling to sign the informed consent
xii)Individuals with other diseases that could interfere
with acupuncture treatment, e.g., clotting disorders
or leukopenia, pace-maker, epilepsy, or anticoagulant
therapy
Recruitment
Patients who have participated in our previous studies
will be contacted to ask if they are interested. Advertise-
ments will be put on notice boards and homepages of
the hospitals, advertising boards on the subway trains,
and local newspapers. Obtaining consent will be carried
out by the investigators with the principle of informed
consent, which consists of information, decisional cap-
acity, and voluntarism. The participants will sign two
written informed consent forms, general consent form
and additional consent provisions for collection and use
of their human biologic material, and go through the
screening test. The model consent form and other re-
lated documentation given to participants can be pro-
vided upon request.
Randomization
After signing an informed consent and undergoing the
screening test, the participants in each hospital will be ran-
domly assigned to one of the two groups using block
randomization. Random numbers will be generated using
the PROC PLAN of SAS 9.2 (SAS Institute Inc., Cary, NC,
USA) by an independent statistician and sent to the Acu-
puncture and Meridian Science Research Center (AMSRC)
at Kyung Hee University where the each randomization
number will be put in a sequentially numbered opaque en-
velope and remain sealed by an administrative staff who is
otherwise not involved in the study.
Once a participant passes the screening test, the inves-
tigator will call the AMSRC staff who is responsible for
this randomization process to give her the hospital
name, and the initial and screening number of the par-
ticipant. The AMSRC staff will then immediately fax a
document containing a unique random number and par-
ticipant group allocation. This feedback document will
be kept in the trial master file.
Intervention
Acupuncture treatment
Detailed information on acupuncture treatment is sum-
marized based on the revised STRICTA recommendations
[29] in Table 1. The acupuncture treatment procedures
were designed to reflect the real clinical setting.
In this trial, partially-individualized manual acupunc-
ture treatments based on the traditional meridian theory
and consensus by the experts in acupuncture and FD,
will be given. The number of inserted needles per par-
ticipant per session ranges from 9 to 19. The acupunc-
ture points consist of basic points and optional points.
All participants will be given needling at nine fixed
points: Large Intestine 4, Stomach (ST) 36, Liver 3, and
Spleen 4 bilaterally, and Conception Vessel 12 unilat-
erally. The optional points include Gallbladder (GB) 21,
Small Intestine (SI) 14, Pericardium (PC) 6, Extra acu-
point of Head and Neck (EX-HN) 5, and ST 34. These
optional points will be selected according to the partici-
pants symptoms such as headache (EX-HN5), shoulder
or back pain (GB21, SI14), nausea and/or vomiting
(PC6), and heartburn or epigastric pain (ST34). Two
additional Ah-Shi points in the medial scapular region
will be allowed in case of shoulder or back pain.
The questions about symptoms related to optional
points will be asked to participants by the clinical re-
search coordinator to minimize the bias induced by con-
tact between doctor and participant.
A sterilized stainless steel needle (40 mm length and
0.25 mm diameter; Dongbang Acupuncture Inc., Bundang,
Sungnam, Korea) will be used. The depth of needle inser-
tion will be from 5 mm to 30 mm and needle manipula-
tion to achieve de qisensation will be performed. The
acupuncture needles will be retained for 15 min.
All acupuncture treatments will be provided by the
same Korean Medicine Doctor at each hospital, who will
have undergone 10 hours of training and simulation
to ensure that they are able to provide identical acu-
puncture treatment in accordance with a pre-defined
protocol.
Acupuncture group
The participants in the acupuncture group will receive
eight acupuncture sessions over 4 weeks. After the treat-
ment period, they will be followed-up for 3 weeks with
Han et al. Trials 2014, 15:89 Page 3 of 9
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Table 1 Acupuncture treatment details based on the STRICTA 2010 checklist [29]
Item Detail
1. Acupuncture rationale 1a) Style of acupuncture
- Manual acupuncture based on traditional meridian theory.
1b) Reasoning for treatment provided, based on historical context, literature sources, and/or consensus methods,
with references where appropriate
- Partially-individualized manual acupuncture treatments based on the traditional meridian theory, clinical experience, and
consensus by the experts in acupuncture and FD.
1c) Extent to which treatment was varied
- Partially-individualized acupuncture treatment, i.e., fixed points plus optional points according to symptoms.
2. Details of needling 2a) Number of needle insertions per subject per session (mean and range where relevant)
- From 9 to 19.
2b) Names (or location if no standard name) of points used (uni/bilateral)
- Nine fixed points: LI4, ST36, LR3, and SP4 (bilateral) and CV12 (unilateral).
- Optional points according to individual symptoms: GB21, SI14, PC6, EX-HN5, and ST34 (bilateral).
2c) Depth of insertion, based on a specified unit of measurement, or on a particular tissue level
- From 5 to 30 mm.
2d) Response sought (e.g., de qi or muscle twitch response)
-De qisensation.
2e) Needle stimulation (e.g., manual, electrical)
- Manual stimulation: needle rotation with thumb and index fingers at 3 Hz.
2f) Needle retention time
- Fifteen minutes.
2g) Needle type (diameter, length, and manufacturer or material)
- A sterilized stainless steel needle (0.25 ×40 mm, Dongbang Acupuncture Inc., Bundang, Sungnam, Korea).
3. Treatment regimen 3a) Number of treatment sessions
- Eight treatment sessions in both acupuncture and waitlist groups.
3b) Frequency and duration of treatment sessions
- Twice weekly for 4 weeks, 15 minutes for each session.
4. Other components of
treatment
4a) Details of other interventions administered to the acupuncture group (e.g., moxibustion, cupping, herbs,
exercises, lifestyle advice)
- No other interventions during the study period allowed.
4b) Setting and context of treatment, including instructions to practitioners, and information and explanations
to patients
- University hospitals.
- Participants will be informed about acupuncture treatment in the study as follows: In this study, acupoint for FD will be
used based on traditional Korean medicine textbook and FD-related reports.
5. Practitioner background 5) Description of participating acupuncturists (qualification or professional affiliation, years in acupuncture
practice, other relevant experience)
- Korean Medicine Doctors who have a license and at least 3 years of experience in gastrointestinal disorders. They went
through 10 hours of training and simulation to ensure that they are able to provide identical acupuncture treatment in
accordance with a pre-defined protocol.
6. Control or comparator
interventions
6a) Rationale for the control or comparator in the context of the research question, with sources that justify this
choice
- A waitlist group will be adopted as a first step before we move on to a sham controlled trial.
6b) Precise description of the control or comparator. If sham acupuncture or any other type of acupuncture-like
control is used, provide details as for items 1 to 3 above.
- Participants in the waitlist will not receive acupuncture treatment after randomization for 4 weeks, during which period,
there will be six telephone visits. After this waiting period, they then will receive twice weekly acupuncture sessions for
4 weeks in the same manner as in the acupuncture group.
CV, Conception Vessel; EX-HN, Extra acupoint of Head and Neck; FD, functiona l dyspepsia; GB, Gallbladder; LI, Large Intestine; LR, Liver; PC, Pericardium; SI, Small
Intestine; SP, Spleen; ST, Stomach; STRICTA, STandards for Reporting Interventions in Clinical Trials of Acupuncture.
Han et al. Trials 2014, 15:89 Page 4 of 9
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six telephone visits to collect adequate relief data and
they will pay a final visit at 8 weeks. No other interven-
tions during the study period will be allowed and a diary
will be collected.
Waitlist group
The participants in the waitlist group will not receive
acupuncture treatment after randomization for 4 weeks,
during which period there will be six telephone visits
once or twice a week. After this waiting period, they will
then receive twice weekly acupuncture sessions for
4 weeks in the same manner as in the acupuncture
group. No other interventions during the study period
will be allowed and a diary will be collected.
Outcome measures
A nurse in each center who is otherwise involved in the
study will give the participants a set of outcome mea-
sures to complete in addition to the primary outcome
measure; its schedule is summarized in Table 2.
Primary outcome
The primary outcome is the proportion of responders
(PR) [30], which is the proportion of subjects who an-
swer yesto more than half of adequate relief questions
in the treatment period. Participants are asked to answer
the following question at each visit during the treatment
period (twice weekly for 4 weeks), at each telephone visit
during the waiting period, and at the follow-up visit:
After the last visit, have you had adequate relief of your
stomach pain or discomfort?Responders are defined as
participants reporting adequate relief for at least 50% of
the study period, i.e., responding Yesmore than four
times out of eight. The proportion of responders will be
compared between the acupuncture group and the wait-
list group.
Secondary outcomes
Nepean Dyspepsia Index Korean version (NDI-K)
The Nepean Dyspepsia Index (NDI) [31,32] is a reliable
and valid measure of QoL in FD. The NDI originally con-
tains 42 items designed to measure symptoms and health-
related QoL in dyspepsia. We will use the Korean version
of NDI (NDI-K), as validated in 2004 by Lee et al. [33],
consisting of two sections about symptom-based ques-
tions and QoL. In this trial, symptom-based questions
such as period, severity, and degree of distress of 15 symp-
toms will be evaluated at baseline, 4 weeks, and 8 weeks.
EuroQol-5 Dimensions (EQ-5D) EuroQol-5 Dimensions
(EQ-5D) [34,35] is one of the standardized preference-
based instruments as a measure of health-related QoL. This
self-report questionnaire consists of an EQ-5D index and
an EQ-5D VAS. To assess the index-based values (utilities),
the three-level version of EQ-5D on five dimensions (mo-
bility, self-care, usual activities, pain/discomfort, and anx-
iety/depression) will be used. EQ-5D VAS records an
individuals rating for his/her current health-related QoL
state on a standard vertical 20 cm VAS (similar to a therm-
ometer) where the endpoints are labelled as best imagin-
able health stateat the top and worst imaginable health
stateat the bottom, respectively. A validated Korean
Table 2 Study schedule for data collection
Measures Baseline 1-week 2-week 3-week 4-week 5-week 6-week 7-week 8-week*
Sociodemographic data
Adequate relief
for the acupuncture group ✔✔✔✔✔✔✔✔✔✔✔✔✔✔ ✔
Adequate relief
§
for the waitlist group ✔✔✔✔✔✔✔✔✔✔✔✔✔✔ ✔
Visual analogue scale for dyspepsia ✔✔
Nepean Dyspepsia Index Korean ✔✔ ✔
Functional Dyspepsia-Related Quality of Life ✔✔ ✔
EuroQol-5 Dimensions ✔✔ ✔
Functional Dyspepsia-related costs ✔✔ ✔
Becks Depression Inventory ✔✔ ✔
The State-Trait Anxiety Inventory ✔✔ ✔
Blood collection for ghrelin analysis ✔✔
Adverse events investigation
✔✔✔✔✔✔✔✔✔✔✔✔✔✔ ✔
Concomitant therapy evaluation ✔✔✔✔✔✔✔✔✔✔✔✔✔✔ ✔
± 1 day interval was allowed for each visit.
*8-week indicates 4 weeks after the 4-week acupuncture treatment.
Adequate relief data will be collected by a telephone interview from 5 to 7 weeks for the acupuncture group.
§
Adequate relief data will be collected by a telephone interview from 1 to 4 weeks for the waitlist group.
Adverse event data for the waitlist group will be collected from 5 to 8 weeks.
Han et al. Trials 2014, 15:89 Page 5 of 9
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version of EQ-5D will be administered in our study [36].
This measurement will be carried out at baseline and after
4and8weeks.
Costs FD-related costs will be assessed using medical re-
cords and a pre-defined questionnaire to collect direct
medical cost including clinic or hospital care and prescrip-
tion or over-the-counter drugs, and direct non-medical
costs including formal/informal care and transportation
costs. Time lost for doctor visits and absence from paid
work due to FD will be taken from patientsself-reported
questionnaires. Direct medical costs used in this study,
such as acupuncture costs, will reflect the real world situ-
ation in Korea from a societal perspective. Additional re-
source consumption data from patients will be measured
at baseline and after 4 and 8 weeks.
Functional Dyspepsia-Related Quality of Life (FD-
QoL) questionnaire The FD-QoL questionnaire is com-
posed of four categories of diet (five items), daily activity
(four items), emotion (six items), and social functioning
(six items). Higher total sum scores of FD-QoL indicate
worse QoL. The questionnaire to be used in this study
was validated among Korean FD patients in the previous
study [37] and the measurement will be done at baseline,
4 weeks, and 8 weeks.
Becks Depression Inventory (BDI) The Becks Depres-
sion Inventory (BDI) [38] is one of the most widely used
instruments for measuring the severity of depression. This
is a self-report inventory and consists of 21 multiple-
choice questions. The participants will complete the BDI
at baseline, 4 weeks, and 8 weeks.
The State-Trait Anxiety Inventory (STAI) The State-
Trait Anxiety Inventory (STAI) [39] is a psychological inven-
tory to evaluate the degree of anxiety based on a 4-point
Likert scale and consists of 40 items on a self-report basis.
The STAI measures two types of anxiety state of anxiety
(20 items; anxiety triggered by a specific event) and trait of
anxiety (20 items; anxiety derived from personal characteris-
tic). Higher scores are positively correlated with higher levels
of anxiety. This measurement will be completed at baseline,
4 weeks, and 8 weeks.
Ghrelin measurement (total ghrelin and deacylated
ghrelin) Ghrelin is mostly secreted by endocrine cells in
the oxyntic mucosa of the stomach [40,41] and is present
in the peripheral circulation as two subtypes: acylated and
unacylated [42]. Its physiologic functions include regulat-
ing food intake [43,44] and secretion of gastric acid [45],
accelerating gastric emptying [46], and stimulating gastric
motility [47,48]. In our study, approximately 6 mL of
whole blood, 3 mL each for total and unacylated ghrelin,
will be collected on an empty stomach at baseline and at
4 weeks. The total and unacylated ghrelin assay will be
performed using the commercially available radio-
immunoassay and enzyme-linked immunosorbent assay
kits.
Sample size calculation
Sample size was determined based on our clinical ex-
perience and previous reports where the waitlist group
achieved approximately 28% of the PR in patients with
irritable bowel syndrome [49]; in our study, we expected
that 60% of the participants on the acupuncture arm
would achieve adequate relief for over a half of the study
period while up to 25% of those on the waitlist arm
would achieve such an outcome. Generally, a level of
significance of α= 0.05 and a power of 1β= 0.80 were
used. The sample size in this trial was estimated accord-
ing to the following formula where (p
t
+p
c
)/2:
n¼Za=2ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
2
p1
pðÞ
pþZβffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
pt1pt
ðÞþpc1pc
ðÞ
q

2
=ptpc
ðÞ
2
Assuming p
t
= 0.6 (p
t
: the effect of the acupuncture
group) and p
c
= 0.25 (p
c
: the effect of the waitlist group),
a sample size of n= 30.1 is calculated to achieve 5% of
significance level and 80% power. Considering an as-
sumed dropout rate of 20%, a total of 76 participants will
be needed with 1:1 allocation to each group (38 partici-
pants per group). First, both centers will respectively re-
cruit 30 patients each. After that, the remaining 16
patients will be recruited and randomized competitively
to include 76 patients in total.
Statistical analysis
A statistical analysis will be performed by an independ-
ent statistician who is blinded to group allocation using
SPSS 21.0 (IBM SPSS Statistics, New York, USA). Our
independent statistician will have an access to the final
dataset which will be kept locked so that investigators
will have limited access. All data will be presented as
means and standard deviations or number (%), and all
analyses will be based on an intention-to-treat principle.
For intention-to-treat analysis, the last observation car-
ried forward rule will be applied. The statistical signifi-
cance level will be set at 0.05 (two-sided), with the 95%
confidence intervals.
Description of baseline characteristics and homogeneity of
the two groups
For the description of baseline characteristics, the mean
with standard deviation or range with minimum and
maximum for continuous data and frequency with per-
centage for dichotomous data will be reported. For the
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homogeneity test of the baseline characteristics between
the two groups, a two-sample t-test for continuous data
and a χ
2
test for dichotomous data will be performed. If
there are baseline characteristics showing statistical signifi-
cance between groups, analysis of covariance (ANCOVA)
or logistic regression will be used for analysis and adjust-
ment of baseline characteristics.
Primary outcome
The primary outcome, PR at 4 weeks, will be compared
between groups using the χ
2
test or logistic regression.
Secondary outcomes
Repeated measure two-factor analysis will be used to
analyze the difference and mean change among baseline,
4 and 8 weeks, difference and mean change between
groups, and interaction between groups and observed
time. For dichotomous outcomes, the χ
2
test or logistic
regression will be used. For the comparison of adverse
events (AEs) between groups, the χ
2
test or Fishers exact
test will be performed.
Data management
To promote data quality, the data will be collected by
well-trained assessor and the double entry of the data
will be implemented by clinical research coordinators.
Safety
We will perform the following tests on all participants at
screening: white blood cell count, hemoglobin, hematocrit,
platelet, aspartate aminotransferase/alanine aminotrans-
ferase, gamma-glutamyl transpeptidase, blood urea nitro-
gen, creatinine, and erythrocyte sedimentation rate. These
tests will help us to exclude participants who have serious
diseases and abnormal liver, heart, kidney, or other organ
function.
Participants will be asked about AEs at each clinic visit
and during the 4-week telephone interviews. AEs will be
defined as any unexpected and unfavorable signs, symp-
toms, or diseases temporally associated with acupuncture
treatment. If any AEs occur, the appropriate treatment will
be provided to the participant immediately. During the
entire study, AEs will be recorded in the dedicated docu-
ment including its severity and causality which will then
be reviewed by the independent monitor.
Any serious AEs that are life-threatening or result in
hospitalization, death, or significant or persistent disabil-
ity will be promptly reported to the clinical research as-
sociate within 24 h from the time of recognition.
Quality control
As we do not expect serious safety concerns, outstand-
ing benefit, or futility in this study, no official Data Mon-
itoring Committee will be established in each hospital.
Instead, to retain the accuracy and quality of the clinical
trial, the clinical research associate will conduct regular
monitoring by checking investigator study files, in-
formed consent forms, case report forms, compliance
with treatments, serious AEs, and data records.
Ethical approval and registration
This trial will be carried out according to the standards
of the International Committee on Harmonization on
Good Clinical Practice and the revised version of the
Declaration of Helsinki. Institutional review boards at
Kyung Hee University Korean Medicine Hospital and
Kyung Hee University Hospital at Gangdong, have ap-
proved an initial version of this protocol (KOMCIRB
201305 for Kyung Hee University Korean Medicine
Hospital and KHNMC-OH-IRB 2013006 for the Kyung
Hee University Hospital at Gangdong) on 28 June and
29 July 2013, respectively. This trial is registered in the
ClinicalTrials.gov (NCT01921504). In addition, all inves-
tigators were trained to maintain the personal informa-
tion of study participants and signed a pledge to protect
the confidentiality of participants.
Discussion
To our knowledge, acupuncture treatment for FD has
not been intensively investigated. This article describes
the protocol of a randomized trial with a waitlist control
group to evaluate the effectiveness of usual acupuncture
practice for FD patients in Korea. We expect that the re-
sults will be able to answer whether acupuncture treat-
ments help adequate symptom improvement and quality
of life, and whether ghrelin secretion is associated with
acupuncture treatment, compared with the no acupunc-
ture group.
A placebo control group is essential to determine the
efficacy of a new treatment. Given that there exist some
published sham-controlled trials of acupuncture for FD
[4,19], some may argue that a sham acupuncture control
should be adopted to investigate specific effect of acu-
puncture. However, it is yet to be clearly understood
what specific components of acupuncture treatment
work in the perceived therapeutic effect of acupuncture
[50]. Sham controls used in the previous studies in-
cluded superficial needling at non-acupuncture points
with [4] or without electrical stimulation [19]. In our
view, none of them are inert, and we could not find any
rationale for a better choice of sham control for our
study. Non-pharmacological intervention studies pose
particular challenges to identify inactive control groups
that generate expectancy comparable to the study inter-
vention [20]. Thus, participants in the non-pharmacological
intervention studies are often randomly allocated to waitlist
control condition as a comparison to the treatment modality
of interest. In this context, we decided to conduct a waitlist
Han et al. Trials 2014, 15:89 Page 7 of 9
http://www.trialsjournal.com/content/15/1/89
controlled trial as a starting point. From this trial, we can in-
vestigate how acupuncture might work against a group
without acupuncture treatment. As natural fluctuations of
symptoms in the disease process and high placebo response
are unique challenges in FD trials, we can also obtain valu-
able information for further studies on how acupuncture
treatment will affect symptoms of FD during the treatment
and over a month of follow-up against a waitlist control.
Additionally, a minimum treatment duration of 4 weeks that
reflects the symptom periodicity is recommended for a
treatment trial for functional gastrointestinal disorders [20].
Therefore, this will be the first Korean randomized con-
trolled trial testing the adequate acupuncture intervention in
terms of duration and reflecting everyday practice.
One of the crucial limitations of this study is that the
doctors and participants cannot be blinded to the group
allocation. Blinding refers to keeping key persons, such
as participants, healthcare providers, outcome assessors,
and data analysts, unaware of the treatment adminis-
tered or of the true hypothesis of the trial [51,52]. Al-
though all outcome measures will be administered and
collected by the blinded nurse to minimize the risk of
detection bias, and a statistician blind to group assign-
ment will perform analysis of the data, the problem of
participant unblinding still remains. We will carefully
discuss residual sources of bias and their potential im-
pact on clinical outcomes when we analyze the study
findings and prepare for publication.
Some may argue that selection of ghrelin as a target
mechanism may provide limited evidence. We under-
stand that a variety of factors have been suggested to be
associated with pathophysiology of FD [24-26]. Among
many, ghrelin has been shown to play an important role
in gastric motility, food intake, and potential gastropro-
tection against acute gastric mucosal injury [25,26].
However, to our best knowledge, there is no report on
how ghrelin is related to acupuncture treatment for FD.
Changes in ghrelin level after acupuncture, therefore,
may not completely explain how acupuncture might
work for symptom improvement in patients with FD.
Nevertheless, ghrelin can be one of the many possible
factors underlying the mechanism of acupuncture for
FD and this study will help add evidence on this.
Trial status
This study is currently recruiting participants. No in-
terim analyses are planned and the primary results will
be published by 2015.
Abbreviations
AEs: Adverse events; AMSRC: Acupuncture and Meridian Science Research
Center; BDI: Becks depression inventory; CV: Conception Vessel; EQ-5D: European
quality of life-5 dimension; EX-HN: Extra acupoint of Head and Neck;
FD:Functionaldyspepsia;FD-QoL:Functional dyspepsia-related quality of life;
GB: Gallbladder; LI: Large Intestine; NDI-K: Nepean dyspepsia index Korean
version; PC: Pericardium; PR: Proportion of responders; QoL: Quality of life;
SI: Small Intestine; ST: Stomach; STAI: State-trait anxiety inventory;
STRICTA: STandards for Reporting Interventions in Clinical Trials of Acupuncture;
VAS: Visual analogue scale.
Competing interests
The authors declare that they have no competing interests.
Authorscontributions
GH: Conception and design, data collection and analysis, manuscript writing,
critical revision, and final approval of the manuscript. SJK: Conception and
design, data collection and analysis, critical revision and final approval of the
manuscript. JWP: Conception and design, data collection and analysis, critical
revision, and final approval of the manuscript. JK: Data collection and
analysis, critical revision and final approval of the manuscript. IY: Statistical
design, data analysis and interpretation, critical revision and final approval of
the manuscript. HJL: Conception and design, financial support, critical
revision and final approval of manuscript. SYK: Design, data analysis and
interpretation, critical revision and final approval of the manuscript. HSL:
Conception and design, data analysis and interpretation, manuscript writing,
critical revision, financial support, and final approval of the manuscript. All
authors read and approved the final manuscript before submission.
Acknowledgements
This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korean government (MSIP, Ministry of Science, ICT
& Future Planning) (No. 20050049404).
Author details
1
Department of Gastroenterology, College of Korean Medicine, Kyung Hee
University, Kyung Hee dae-ro 26, Dongdaemun-gu, Seoul 130-701, Republic
of Korea.
2
Department of Statistics, Sookmyung Womens University,
Cheongpa-ro 47-gil 100, Youngsan-gu, Seoul 140-742, Republic of Korea.
3
Acupuncture and Meridian Science Research Center, College of Korean
Medicine, Kyung Hee University, Kyung Hee dae-ro 26, Dongdaemun-gu,
Seoul 130-701, South Korea.
Received: 25 November 2013 Accepted: 4 March 2014
Published: 22 March 2014
References
1. Oustamanolakis P, Tack J: Dyspepsia: organic versus functional. J Clin
Gastroenterol 2012, 46:175190.
2. Ghoshal UC, Singh R, Chang FY, Hou X, Wong BC, Kachintorn U:
Epidemiology of uninvestigated and functional dyspepsia in Asia: facts
and fiction. J Neurogastroenterol Motil 2011, 17:235244.
3. Lee JS: The guideline for diagnosis of functional dyspepsia. Kor J
Neuroenterol Motil 2005, 11:1824.
4. Ma TT, Yu SY, Li Y, Liang FR, Tian XP, Zheng H, Yan J, Sun GJ, Chang XR,
Zhao L, Wu X, Zeng F: Randomised clinical trial: an assessment of
acupuncture on specific meridian or specific acupoint vs. sham
acupuncture for treating functional dyspepsia. Aliment Pharmacol Ther
2012, 35:552561.
5. Moayyedi P, Delaney BC, Vakil N, Forman D, Talley NJ: The efficacy of
proton pump inhibitors in nonulcer dyspepsia: a systematic review and
economic analysis. Gastroenterology 2004, 127:13291337.
6. Soo S, Forman D, Delaney BC, Moayyedi P: A systematic review of
psychological therapies for nonulcer dyspepsia. Am J Gastroenterol
18171822, 2004:99.
7. Hiyama T, Yoshihara M, Matsuo K, Kusunoki H, Kamada T, Ito M, Tanaka S,
Nishi N, Chayama K, Haruma K: Meta-analysis of the effects of prokinetic
agents in patients with functional dyspepsia. J Gastroenterol Hepatol 2007,
22:304310.
8. Talley NJ, Tack J, Ptak T, Gupta R, Giguere M: Itopride in functional
dyspepsia: results of two phase III multicentre, randomised, double-blind,
placebo-controlled trials. Gut 2008, 57:740746.
9. Lacy BE, Talley NJ, Locke GR 3rd, Bouras EP, DiBaise JK, El-Serag HB, Abraham
BP, Howden CW, Moayyedi P, Prather C: Review article: current treatment
options and management of functional dyspepsia. Aliment Pharmacol
Ther 2012, 36:315.
Han et al. Trials 2014, 15:89 Page 8 of 9
http://www.trialsjournal.com/content/15/1/89
10. Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D:
Pharmacological interventions for non-ulcer dyspepsia. Cochrane
Database Syst Rev 2006, 2006:CD001960.
11. Lei L, Fang Z, Guang JL, Li Y, Xi W, Lan ML: Acupuncture for functional
dyspepsia. The Cochrane Library 2010.
12. Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Foster NE,
Sherman KJ, Witt CM, Linde K: Acupuncture for chronic pain: individual
patient data meta-analysis. Arch Intern Med 2012, 172:14441453.
13. Noguchi E: Acupuncture regulates gut motility and secretion via nerve
reflexes. Auton Neurosci 2010, 156:1518.
14. Van Oudenhove L, Aziz Q: The role of psychosocial factors and psychiatric
disorders in functional dyspepsia. Nat Rev Gastroenterol Hepatol 2013,
10:158167.
15. Quartero AO, Post MW, Numans ME, de Melker RA, de Wit NJ: What makes
the dyspeptic patient feel ill? A cross sectional survey of functional
health status, Helicobacter pylori infection, and psychological distress in
dyspeptic patients in general practice. Gut 1999, 45:1519.
16. Errington-Evans N: Acupuncture for anxiety. CNS Neurosci Ther 2012,
18:277284.
17. MacPherson H, Richmond S, Bland M, Brealey S, Gabe R, Hopton A, Keding
A, Lansdown H, Perren S, Sculpher M, Spackman E, Torgerson D, Watt I:
Acupuncture and counselling for depression in primary care: a
randomised controlled trial. PLoS Med 2013, 10:e1001518.
18. Park HJ, Kim HY, Hahm DH, Lee H, Kim KS, Shim I: Electroacupuncture to
ST36 ameliorates behavioral and biochemical responses to restraint
stress in rats. Neurol Res 2010, 32:111115.
19. Park YC, Kang W, Choi SM, Son CG: Evaluation of manual acupuncture at
classical and nondefined points for treatment of functional dyspepsia: a
randomized-controlled trial. J Altern Complement Med 2009, 15:879884.
20. Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ,
Veldhuyzen van Zanten SJ: Design of treatment trials for functional
gastrointestinal disorders. Gastroenterology 2006, 130:15381551.
21. Zhu H: A Cochrane Systematic Review on Acupuncture for Functional
Dyspepsia, Masters Thesis. Chengdu: Chengdu University of Traditional
Chinese Medicine; 2008 [In Chinese].
22. Lundeberg T, Lund I, Naslund J, Thomas M: The Emperors sham wrong
assumption that sham needling is sham. Acupunct Med 2008, 26:239242.
23. Moffet HH: Sham acupuncture may be as efficacious as true
acupuncture: a systematic review of clinical trials. J Altern Complement
Med 2009, 15:213216.
24. Toyoshima F, Oshima T, Nakajima S, Sakurai J, Tanaka J, Tomita T, Hori K,
Matsumoto T, Miwa H: Serotonin transporter gene polymorphism may be
associated with functional dyspepsia in a Japanese population. BMC Med
Genet 2011, 12:88.
25. Szlachcic A, Brzozowski T, Majka J, Pajdo R, Konturek PC, Pawlik M, Kwiecien
S, Drozdowicz D, Bielanski W, Konturek SJ, Pawlik WW: Involvement of
orexigenic peptides in the mechanism of gastric mucosal integrity and
healing of chronic gastric ulcers. Curr Pharm Des 2010, 16:12141223.
26. Yagi T, Asakawa A, Ueda H, Miyawaki S, Inui A: The role of ghrelin in
patients with functional dyspepsia and its potential clinical relevance
(Review). Int J Mol Med 2013, 32:523531.
27. Gucel F, Bahar B, Demirtas C, Mit S, Cevik C: Influence of acupuncture on
leptin, ghrelin, insulin and cholecystokinin in obese women: a
randomised, sham-controlled preliminary trial. Acupunct Med 2012,
30:203207.
28. Tian N, Wang F, Tian DR, Zou Y, Wang SW, Guan LL, Shi YS, Chang JK, Yang J,
Han JS: Electroacupuncture suppresses expression of gastric ghrelin and
hypothalamic NPY in chronic food restricted rats. Peptides 2006, 27:23132320.
29. MacPherson H, Altman DG, Hammerschlag R, Youping L, Taixiang W, White
A, Moher D: Revised STandards for Reporting Interventions in Clinical
Trials of Acupuncture (STRICTA): extending the CONSORT statement.
PLoS Med 2010, 7:e1000261.
30. Talley NJ, Veldhuyzen van Zanten SJ, Saez LR, Dukes G, Perschy T, Heath M,
Kleoudis C, Mangel AW: A dose-ranging, placebo-controlled, randomized
trial of alosetron in patients with functional dyspepsia. Aliment Pharmacol
Ther 2001, 15:525537.
31. Talley NJ, Haque M, Wyeth JW, Stace NH, Tytgat GN, Stanghellini V,
Holtmann G, Verlinden M, Jones M: Development of a new dyspepsia
impact scale: the Nepean dyspepsia index. Aliment Pharmacol Ther 1999,
13:225235.
32. Talley NJ, Verlinden M, Jones M: Quality of life in functional dyspepsia:
responsiveness of the Nepean dyspepsia index and development of a
new 10-item short form. Aliment Pharmacol Ther 2001, 15:207216.
33. Lee SY, Choi SC, Cho YK, Choi MG: Validation of the Nepean dyspepsia
index- Korean version. Kor J Neurogastroenterol Mot 2003, 9(suppl):48S.
34. Mahadeva S, Wee HL, Goh KL, Thumboo J: The EQ-5D (Euroqol) is a valid
generic instrument for measuring quality of life in patients with
dyspepsia. BMC Gastroenterol 2009, 9:20.
35. Drummond MF, Sculpher MJ, Torrance GW, OBrien BJ, Stoddart G: Methods
for the Economic Evaluation of Health Care Programmes. 3rd edition. New
York: Oxford University Press; 2005.
36. Kang EJ, Shin SH, Park HJ, Jo MW, Kim NY: A validation of health status
using EQ-5D. Kor J Health Econ Policy 2006, 12:1943.
37. Lee EH, Hahm KB, Lee JH, Park JJ, Lee DH, Kim SK, Choi SR, Lee ST:
Development and validation of a functional dyspepsia-related quality of
life (FD-QOL) scale in South Korea. J Gastroenterol Hepatol 2006, 21:268274.
38. Beck AT, Rial WY, Rickels K: Short form of depression inventory: cross-validation.
Psychol Rep 1974, 34:11841186.
39. Spielberger CD, Goursuch RL, Lushene RE: Manual for the State Trait Anxiety
Inventory. Mountain View, CA: Consulting Psychologist Press; 1983.
40. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T,
Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M,
Kangawa K, Nakao K: Stomach is a major source of circulating ghrelin, and
feeding state determines plasma ghrelin-like immunoreactivity levels in
humans. J Clin Endocrinol Metab 2001, 86:47534758.
41. Krsek M, Rosicka M, Haluzik M, Svobodova J, Kotrlikova E, Justova V,
Lacinova Z, Jarkovska Z: Plasma ghrelin levels in patients with short
bowel syndrome. Endocr Res 2002, 28:2733.
42. Akamizu T, Shinomiya T, Irako T, Fukunaga M, Nakai Y, Nakai Y, Kangawa K:
Separate measurement of plasma levels of acylated and desacyl ghrelin
in healthy subjects using a new direct ELISA assay. J Clin Endocrinol
Metab 2005, 90:69.
43. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS,
Ghatei MA, Bloom SR: Ghrelin enhances appetite and increases food
intake in humans. J Clin Endocrinol Metab 2001, 86:5992.
44. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S,
Fujimiya M, Niijima A, Fujino MA, Kasuga M: Ghrelin is an appetite-stimulatory
signal from stomach with structural resemblance to motilin. Gastroenterology
2001, 120:337345.
45. Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S:
Ghrelin acts in the central nervous system to stimulate gastric acid
secretion. Biochem Biophys Res Commun 2001, 280:904907.
46. Sibilia V, Rindi G, Pagani F, Rapetti D, Locatelli V, Torsello A, Campanini N,
Deghenghi R, Netti C: Ghrelin protects against ethanol-induced gastric
ulcers in rats: studies on the mechanisms of action. Endocrinology 2003,
144:353359.
47. Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H,
Kojima M, Kangawa K: Ghrelin stimulates gastric acid secretion and
motility in rats. Biochem Biophys Res Commun 2000, 276(3):905908.
48. Kojima M, Kangawa K: Structure and function of ghrelin. Results Probl Cell
Differ 2008, 46:89115.
49. Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, Kirsch I,
Schyner RN, Nam BH, Nguyen LT, Park M, Rivers AL, McManus C, Kokkotou E,
Drossman DA, Goldman P, Lembo AJ: Components of placebo effect:
randomised controlled trial in patients with irritable bowel syndrome. BMJ
2008, 336:9991003.
50. Langevin HM, Wayne PM, Macpherson H, Schnyer R, Milley RM, Napadow V,
Lao L, Park J, Harris RE, Cohen M, Sherman KJ, Haramati A, Hammerschlag R:
Paradoxes in acupuncture research: strategies for moving forward. Evid
Based Complement Alternat Med 2011, 2011:180805.
51. Schulz KF, Chalmers I, Altman DG: The landscape and lexicon of blinding
in randomized trials. Ann Intern Med 2002, 136:254259.
52. Park J, Lee H, White A, Ernst E: Suggesting an alternative to the term
double-blind.Anesthesiology 2002, 96:1034. Author reply 1035.
doi:10.1186/1745-6215-15-89
Cite this article as: Han et al.:Acupuncture for functional dyspepsia:
study protocol for a two-center, randomized controlled trial. Trials
2014 15:89.
Han et al. Trials 2014, 15:89 Page 9 of 9
http://www.trialsjournal.com/content/15/1/89
... 9,10 AT for FD has been practiced in Asia for thousands of years. 9,11 However, evidence for the therapeutic effects of AT is still limited by the lack of high-quality clinical trials. 10,12 Furthermore, few clinical trials reflecting the real practice of AT have been conducted to date. ...
... (identifier: NCT01921504). 11 ...
... Inclusion and exclusion criteria were detailed in the previous protocol study. 11 Randomization A random allocation table sequence was created by an independent statistician using block randomization. Random numbers were generated by using the PROC PLAN of SAS 9.2 (SAS Institute, Inc., Cary, NC). ...
Article
Objectives: This study was implemented to evaluate the effect of individualized acupuncture treatment (AT) on functional dyspepsia (FD). Methods: A randomized, waitlist-controlled, two-center trial was performed. Seventy-six patients with FD were enrolled in the trial with partially individualized AT in a more realistic clinical setting performed twice a week for 15 minutes a session over 4 weeks. The participants were randomly allocated to a group receiving 8 sessions of AT for 4 weeks or a waitlist control group. After 4 consecutive weeks, the AT group was followed up without AT and the control group received the identical AT. The proportion of responders with adequate symptom relief, Nepean Dyspepsia Index (NDI), FD-related quality of life, Beck Depression Inventory, State-Trait Anxiety Inventory, Acupuncture Belief Scale, and acupuncture credibility test were assessed. Results: After the first 4 weeks, the proportion of responders significantly improved (59% in AT group [n = 37] versus 3% in control group [n = 39]; p < 0.001). The difference was no longer significant at 8 weeks, at which point the waitlist control group showed similar improvement after receiving AT (68% in the AT group versus 79% in the control group). Total NDI scores were significantly reduced in the AT group compared with the waitlist group (p = 0.03). Among NDI items, discomfort (p = 0.01), burning (p = 0.02), fullness after eating (p = 0.02), and burping (p = 0.02) were significantly improved in the AT group compared with the control group. No significant differences were observed between groups in other secondary variables. Conclusion: Individualized AT adequately relieves symptoms in patients with FD, and this effect may persist up to 8 weeks.
... We set the "proportion of responders" (PR) [28,29] as the primary outcome. PR is the proportion of participants who respond "yes" to more than half of the ARrelated questions during the treatment period [30]. An assessor will ask the participants the following question at each visit during the treatment period (twice a week for 6 weeks): "Have you had adequate relief of the pain or discomfort caused to you by GERD since the last visit?" ...
... The EuroQol-5 Dimension (EQ-5D) [44] will be used to evaluate the participants' QoL. The EQ-5D is a standardized preference-based questionnaire for measuring health-related QoL [30]; it consists of the EQ-5D index and the EQ-5D visual analog scale (VAS). The EQ-5D index is calculated on the basis of five dimensions: mobility, self-care, ability to undertake usual activities, pain, and anxiety/depression. ...
... One report addressing functional gastrointestinal disorders (FGIDs) recommended that participants be classified as either responders or nonresponders in terms of the primary outcome [28], whereas another study showed that a responder analysis may be an important addition to clinical trial reporting [59]. Still another [30] used PR as a primary outcome for evaluating the effect of acupuncture in functional dyspepsia, which is one of the FGIDs. Hence, we will also use PR as a primary outcome in this trial. ...
Article
Full-text available
Background: Gastroesophageal reflux disease lowers the quality of life and increases medical costs. Electroacupuncture has been used to ease symptoms and improve gastrointestinal motility in patients with gastroesophageal reflux disease. The main purposes of this study are to evaluate the efficacy and safety of this procedure. Methods/design: This is a protocol for a randomized, patient-blinded, assessor-blinded, sham-controlled trial. Sixty participants with symptoms of gastroesophageal reflux disease, who have previously undergone standard treatment, will be recruited from August 2015 at Kyung Hee University Korean Medicine Hospital. The participants will be allocated to either the electroacupuncture (n = 30) or the sham electroacupuncture group (n = 30); the allocation will be concealed from both the participants and the assessors. The EA group will undergo penetrating acupuncture at 18 fixed points and two optional points chosen using the pattern identification for gastroesophageal reflux disease. Electrical stimulation will be applied at some of the acupoints. The sham electroacupuncture group will undergo nonpenetrating acupuncture without electrical stimulation at 18 nonspecific points, each of which will be only 2 cm away from the true acupoints used in the electroacupuncture group. In both groups, the procedure will be performed using the Park device. The treatment will last for 6 weeks (with two sessions each week), and the outcome will be evaluated at baseline, 3 weeks, and 6 weeks. The primary outcome will be the proportion of responders with adequate symptom relief, whereas the secondary outcomes will comprise the results of the Nepean dyspepsia index; the Korean gastrointestinal symptom rating scale; the EQ-5D™; levels of gastrin, motilin, and inflammatory cytokines; the perceived stress scale; the qi-stagnation questionnaire; the patient global impression of change; and the spleen qi deficiency questionnaire. Discussion: The results of this trial will provide information about the efficacy and safety of electroacupuncture in the treatment of gastroesophageal reflux disease symptoms, as well as evidence regarding the use of electroacupuncture to treat gastroesophageal reflux disease in real clinical practice. Trial registration: Clinical Research Information Service Identifier, KCT0001653 . Registered on 12 October 2015.
... Acupuncture is widely used as a surface stimulating therapy for gastrointestinal disorders. Studies have shown that acupuncture may be efficacious in treating DGBI, including functional dyspepsia (FD), irritable bowel syndrome (IBS), and functional constipation (FC) 22,23 (Table 1). Acupuncture is a safe therapy with a low risk of adverse events 24,25 . ...
... The acupoints ST36, CV12, LI4, and LR3, which were frequently selected in our analysis, were consistent with those selected in clinical trials of FD published over the years. [37][38][39][40] Additionally, in our analysis, the five transport points GB41, HT8, HT7, SI5, LR1, and LR2, used for Sa-am acupuncture therapy were more frequently selected in the pattern-specific scenario. Sa-am acupuncture provides basic acupuncture prescriptions to restore balance by applying the engendering and restraining cycle relationships using the five transport points on the 12 meridians. ...
Article
Full-text available
Background Clinical research in acupuncture has been criticized for not reflecting real-world practice in terms of diagnosis and intervention. This study aimed to collect data on the principles of diagnosis and selection of acupoints from Korean medicine doctors (KMDs) and analyze the patterns and priorities in decision-making. Methods The study design was based on the data of an actual patient with functional dyspepsia (FD) (according to Rome III criteria) to create simulated patients, and a KMD specialized in gastrointestinal disorders was allocated to collect the clinical information as objectively as possible. Sixty-nine KMDs were recruited to diagnose a simulated patient based on the actual patient's clinical information, in a manner similar to that performed in their clinics. Results After the diagnostic procedures were completed, the pattern identification, selected acupoints, reasons for choosing them, and importance of symptoms for deciding their diagnoses were documented. The information needed was clearly distinguishable from those routinely asked in western medicine, and information regarding fecal status, abdominal examination, appetite status, pulse diagnosis, and tongue diagnosis were listed as vital. The doctors identified the patient's pattern as “spleen-stomach weakness,” “liver qi depression,” or “food accumulation or phlegm-fluid retention.” The most frequently selected acupoints were CV12, LI4, LR3, ST36, and PC6. Conclusion There are common acupoints across different patterns, but pattern-specific acupoints were also recommended. These results can provide useful information to design clinical research and education for better clinical performance in acupuncture that reflects real-world practice.
... As chamadas terapias complementares ou alternativas (ervas chinesas, japonesas e indianas, acupuntura) e/ou o tratamento psicológico (hipnose, psicoterapia e terapia cognitiva comportamental) têm sido muito utilizadas por um grupo de pesquisadores e devem ser consideradas para pacientes que não respondem ao tratamento farmacológico [35][36][37][38] . Vários estudos têm demonstrado resultados animadores com esse tipo de abordagem no tratamento da DF. ...
... Acupuncture treatment is one of the most sought-after therapeutic modalities in complementary and alternative medicine [3]. It is a safe medical procedure with minimal side effects. ...
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Full-text available
Background Acupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the effect of different acupoint combinations on controlling CINV remains unknown. This study aims to compare the effects of distal-proximal point association and local distribution point association on controlling CINV. Methods/design The study is a single-center, randomized controlled trial. A total of 240 participants will be randomly divided into four groups. The control group will receive standard antiemetic only, whereas three acupuncture groups will receive four electro-acupuncture treatments once a day with the standard antiemetic. Acupuncture group I and II will receive distal-proximal point association (“Neiguan (PC6) and Zhongwan (CV12)”, and “Zusanli (ST36) and CV12”, respectively); Acupuncture group III will receive local distribution point association (“Shangwan (CV13) and CV12”). The primary outcome measures are the frequency and distress of nausea and vomiting. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, quality of life, etc. Assessment is scheduled from the day before chemotherapy to the fifth day of chemotherapy. Follow-ups are performed from the sixth day to the twenty-first day of chemotherapy. Discussion Results of this trial will help in evaluating the efficacy and safety of electro-acupuncture with different acupoint combinations in the management of CINV. Trial registration ClinicalTrials.gov identifier: NCT02478047.
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Acupuncture has been used in China for thousands of years and has become more widely accepted by doctors and patients around the world. A large number of clinical studies and animal experiments have confirmed that acupuncture has a benign adjustment effect on gastrointestinal (GI) movement; however, the mechanism of this effect is unclear, especially in terms of neural mechanisms, and there are still many areas that require further exploration. This article reviews the recent data on the neural mechanism of acupuncture on GI movements. We summarize the neural mechanism of acupuncture on GI movement from four aspects: acupuncture signal transmission, the sympathetic and parasympathetic nervous system, the enteric nervous system, and the central nervous system.
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Funktionelle Dyspepsie (FD) ist eine in der Allgemeinbevölkerung vorherrschende gastrointestinale Störung mit einer komplexen Pathogenese. Viele PatientInnen mit FD wenden wegen fehlender zufriedenstellender Linderung durch die herkömmlichen Behandlungen komplementäre Therapien an. Akupunktur wird seit tausenden Jahren in China angewendet und soll bei der Behandlung von funktionellen Magen-Darm-Störungen hilfreich sein. Dieser Übersichtsbeitrag diskutiert die Forschungen über Effekte und Mechanismen der Akupunktur bei FD. Studien deuten darauf hin, dass Akupunktur bei der Verbesserung der Symptome und der Lebensqualität von FD-PatientInnen von Vorteil sein kann. Die zugrunde liegenden Mechanismen der Akupunktur für FD umfassen die Verbesserung der verzögerten Magen-Darm-Entleerung und gestörten Nahrungsaufnahme sowie die Verringerung der Überempfindlichkeit gegenüber Magendehnung. Wenn der Unterschied zwischen den FD-Unterkategorien und der Messung des klinischen Ergebnisses stärker berücksichtigt wird, werden die tatsächlichen Auswirkungen der Akupunktur möglicherweise noch besser sichtbar. Neben allgemeinen Betrachtungen wird auch ein Studiendesign zur Realisierung eigener Forschungsvorhaben vorgestellt.
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Background: Bu-Zhong-Yi-Qi-Tang (BZYQT) has long been used for the treatment of severe weakness caused by general fatigue, loss of appetite, or indigestion. The aim of this feasibility study is to assess the effectiveness and safety of BZYQT for the treatment of functional dyspepsia (FD) with spleen qi deficiency. Methods: This study will be conducted at a single center as a prospective, nonrandomized, nonblinded, single-arm feasibility study. A total of 30 participants diagnosed with FD in accordance with the Rome III criteria will be enrolled. All patients will receive BZYQT for 4 weeks. The primary outcome is the change in the Nepean Dyspepsia Index-Korean version (NDI-K) scores between the baseline and 4-week images. The secondary outcomes include the tongue coating thickness, blood parameters, and BZYQT Questionnaire score. The NDI-K score will be acquired four times, at Weeks 0 (baseline), 2 (during treatment), 4 (after treatment), and 8 (after follow-up). Written informed consent will be obtained from all study participants prior to enrollment. This study has been approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital. This study protocol is registered with the national clinical trial registry of the World Health Organization International Clinical Trials Registry Platform. Results will be published in a journal and will be disseminated both electronically and in print. Discussion: The results of this study may serve as a guide for researchers seeking to effectively evaluate the effects of BZYQT. Trial Registration No.: KCT0002114 (date of registration: October 21, 2016).
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Introduction The SPIRIT Statement was published to improve the completeness and transparency of clinical trial protocols. However, a number of protocols have failed to meet these significant standards. How well acupuncture trial protocols adhere to standards, and what items are usually lacking remain unanswered. This study is to assess the reporting quality of study protocols regarding randomized clinical trials of acupuncture using the SPIRIT Statement. Methods A literature search on acupuncture trial protocols was conducted using the following databases: PubMed, EMBASE, SCI Expanded, The Cochrane library, and four Chinese Databases. We extracted data and inputted them into pre-prepared Excel forms. We assessed the reporting quality of these acupuncture trial protocols as compared against the SPIRIT checklists, and made a comparison before and after its release. Results We included 142 appropriate protocols, but none reported complete information. In general, the items that were often ignored in acupuncture protocols are the following: Protocol version, Roles and responsibilities, Interventions, Blinding, Data management, Statistical analysis, Data monitoring, Auditing, Protocol amendments, Consent or assent, Confidentiality, Access to data, Ancillary and post-trial care, Dissemination policy, and Appendices. There was no statistical difference before and after the release of SPIRIT, but except for five items in the aspects of; trial registration, study setting, participant timeline, and allocation concealment. Conclusions Study protocols of randomized clinical trials on acupuncture have not provided information as thoroughly as recommended in the SPIRIT Statement. Our study emphasizes the importance of comprehensive standards for trial protocols in the drafting of high-quality protocols for acupuncture.
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Depression is a significant cause of morbidity. Many patients have communicated an interest in non-pharmacological therapies to their general practitioners. Systematic reviews of acupuncture and counselling for depression in primary care have identified limited evidence. The aim of this study was to evaluate acupuncture versus usual care and counselling versus usual care for patients who continue to experience depression in primary care. In a randomised controlled trial, 755 patients with depression (Beck Depression Inventory BDI-II score ≥20) were recruited from 27 primary care practices in the North of England. Patients were randomised to one of three arms using a ratio of 2∶2∶1 to acupuncture (302), counselling (302), and usual care alone (151). The primary outcome was the difference in mean Patient Health Questionnaire (PHQ-9) scores at 3 months with secondary analyses over 12 months follow-up. Analysis was by intention-to-treat. PHQ-9 data were available for 614 patients at 3 months and 572 patients at 12 months. Patients attended a mean of ten sessions for acupuncture and nine sessions for counselling. Compared to usual care, there was a statistically significant reduction in mean PHQ-9 depression scores at 3 months for acupuncture (-2.46, 95% CI -3.72 to -1.21) and counselling (-1.73, 95% CI -3.00 to -0.45), and over 12 months for acupuncture (-1.55, 95% CI -2.41 to -0.70) and counselling (-1.50, 95% CI -2.43 to -0.58). Differences between acupuncture and counselling were not significant. In terms of limitations, the trial was not designed to separate out specific from non-specific effects. No serious treatment-related adverse events were reported. In this randomised controlled trial of acupuncture and counselling for patients presenting with depression, after having consulted their general practitioner in primary care, both interventions were associated with significantly reduced depression at 3 months when compared to usual care alone. Controlled-Trials.com ISRCTN63787732 Please see later in the article for the Editors' Summary.
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Functional dyspepsia (FD) is a functional gastrointestinal disorder (FGID). According to the Rome III consensus, FD is divided into 2 subgroups: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Although multiple mechanisms of FD pathogenesis have been suggested, its underlying etiology and pharmacological therapy remain unclear. Ghrelin is a gut-derived peptide found in the stomach. It plays a role in the regulation of gastric motility and appetite. The ghrelin gene encodes 3 molecular forms, acyl ghrelin, des-acyl ghrelin and obestatin. Acyl ghrelin acts as an endogenous ligand for growth hormone secretagogue receptor; furthermore, it is orexigenic, with effects on food intake, energy homeostasis and gastrointestinal motility. Des-acyl ghrelin exerts an opposite effect to acyl ghrelin. Obestatin exerts an inhibitory effect on the motor activity of the antrum and duodenum in fed animals. These peptides exert differential effects on gut motility and food intake. The therapeutic potential of ghrelin has attracted attention due to its varied bioactivities. Certain studies have shown that total ghrelin levels are significantly lower in patients with FD compared with healthy volunteers and that the acyl ghrelin levels of patients with FD are higher compared with healthy volunteers. However, a recent study demonstrated that acyl ghrelin levels in patients with PDS were lower compared with healthy volunteers; the association between FD and other ghrelin family gene products also remains unclear. Although certain studies have demonstrated the beneficial effects of acyl ghrelin administration and its agonist in patients with FD, only a few clinical reports exist. Further studies are required in order to examine the effects of ghrelin on FD.
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• Functional dyspepsia is characterised by a history of at least three months of chronic dyspeptic symptoms in the absence of any relevant organic disease. • Individual dyspeptic symptoms or groups of symptoms cannot be used to help distinguish organic dyspesia (ie. that caused by chronic peptic ulcer disease, gastro-oesophageal reflux or malignancy) from functional dyspepsia. Therefore it is often difficult to distinguish between these conditions without investigations. • Empirical therapy for dyspepsia involves testing for Helicobacter pylori and treating if infected, followed by acid suppression with a proton pump inhibitor (PPI) if symptoms remain, or if negative for H. pylori a trial of PPI therapy. • Endoscopy should be performed before H. pylori testing and treatment in patients with new symptoms who are older than 55 years or who have alarm symptoms. • If acid suppression fails in a patient in whom H. pylori has been excluded or eradicated, the symptoms and diagnosis should be reappraised. Prokinetics, antidepressants, psychological therapies or complementary therapies may be helpful. • Alarm features (red flags) for upper gastrointestinal malignancy include onset of dyspepsia at an older age (over 55 years), a family history of upper gastrointestinal cancer or symptoms such as unexplained weight loss, recurrent vomiting or progressive dysphagia.
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Background Although acupuncture is widely used for chronic pain, there remains considerable controversy as to its value. We aimed to determine the effect size of acupuncture for 4 chronic pain conditions: back and neck pain, osteoarthritis, chronic headache, and shoulder pain. Methods We conducted a systematic review to identify randomized controlled trials (RCTs) of acupuncture for chronic pain in which allocation concealment was determined unambiguously to be adequate. Individual patient data meta-analyses were conducted using data from 29 of 31 eligible RCTs, with a total of 17 922 patients analyzed. Results In the primary analysis, including all eligible RCTs, acupuncture was superior to both sham and no-acupuncture control for each pain condition (P < .001 for all comparisons). After exclusion of an outlying set of RCTs that strongly favored acupuncture, the effect sizes were similar across pain conditions. Patients receiving acupuncture had less pain, with scores that were 0.23 (95% CI, 0.13–0.33), 0.16 (95% CI, 0.07–0.25), and 0.15 (95% CI, 0.07–0.24) SDs lower than sham controls for back and neck pain, osteoarthritis, and chronic headache, respectively; the effect sizes in comparison to no-acupuncture controls were 0.55 (95% CI, 0.51–0.58), 0.57 (95% CI, 0.50–0.64), and 0.42 (95% CI, 0.37–0.46) SDs. These results were robust to a variety of sensitivity analyses, including those related to publication bias. Conclusions Acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo. However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.