Content uploaded by Kunhyung Kim
Author content
All content in this area was uploaded by Kunhyung Kim on Jan 08, 2014
Content may be subject to copyright.
Available via license: CC BY 2.0
Content may be subject to copyright.
S T U D Y P R O T O C O L Open Access
Moxibustion for treating knee osteoarthritis:
study protocol of a multicentre randomised
controlled trial
Seunghoon Lee
1,2
, Kun Hyung Kim
3
, Tae-Hun Kim
4
, Jung-Eun Kim
1
, Joo-Hee Kim
1,2
, Jung Won Kang
2
,
Kyung-Won Kang
1
, So-Young Jung
1
, Ae-Ran Kim
1
, Hyo-Ju Park
1
, Mi-Suk Shin
1
, Kwon-Eui Hong
5
, Ho-Sueb Song
6
,
Jin-Bong Choi
7
, Hyung-Jun Kim
8
and Sun-Mi Choi
1*
Abstract
Background: The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is
typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion
has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity.
However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for
treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety,
cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual
care.
Methods/designs: This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-
group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care
group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive
moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and
SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive
moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after
random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional
medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments.
Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be
provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-
WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and
function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical
Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to
evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation
and a qualitative study will be conducted as a mixed-methods approach.
Discussion: This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for
treating knee osteoarthritis.
Trial registration: Clinical Research information Service: KCT0000130
* Correspondence: smchoi@kiom.re.kr
1
Acupuncture, Moxibustion & Meridian Research Group, Medical Research
Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
Full list of author information is available at the end of the article
© 2013 Lee 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 cited.
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59
http://www.biomedcentral.com/1472-6882/13/59
Background
Osteoarthritis (OA) is the most common form of ar-
thritis in the elderly, and it is characterised by pain and
functional limitation, leading to a reduction in quality of
life [1,2]. It is an active disease process involving the
focal loss of articular cartilage, subchondral bone thi-
ckening, and new bone formation [3].
Non-steroidal anti-inflammatory drugs (NSAIDs) and
acetaminophen are the most common pharmacological
agents used to treat OA. However, according to recent
studies, these products only help to slightly reduce short-
term pain and do not inhibit disease progression [4,5].
Furthermore, these drugs are associated with adverse
events, such as gastrointestinal irritation and bleeding,
perforating ulcers, and renal and hepatic toxicity. There-
fore, patients who experience unsatisfactory results and a
risk of adverse events using pharmacological agents are
recommended to pursue non-pharmacological treatments,
including complementary and alternative medicines, such
as acupuncture and moxibustion [6].
Moxibustion is a traditional oriental therapy that treats
diseases through thermal stimulation by burning herbs,
primarily Artemisia vulgaris, at specific spots on the skin
[7]. It has been used for various diseases, such as OA,
stroke, and hot flushes, in addition to acupuncture in
the traditional medical systems of Korea, China, Japan,
Vietnam, and Mongolia [8].
Acupuncture has been studied sufficiently to demon-
strate that it has benefits for peripheral knee osteoarthritis
(KOA) [6,9]. One systematic review evaluated acupunc-
ture for peripheral joint OA and included 14 randomised
controlled trials (RCTs) for KOA (a total of 18 RCTs);
acupuncture was shown to be efficacious for pain control
in KOA in sham-controlled RCTs [6]. In the Cochrane
review, the authors concluded that acupuncture for pe-
ripheral joint OA had statistically significant and clinically
relevant benefits in waiting list-controlled trials [9].
However, according to a recent systematic review [10]
on the use of moxibustion for rheumatic conditions,
only 4 RCTs [11-14] on KOA using moxibustion have
been published, and it is difficult to provide conclusive
evidence for the effectiveness of moxibustion in treating
rheumatic conditions, including KOA because of a high
risk of bias with low methodological quality. Therefore,
high-quality studies following the CONSORT 2010
Statement and revised STRICTA are necessary to deter-
mine whether moxibustion is an effective treatment for
KOA [15,16]. In addition, even if a placebo moxibustion
procedure was developed, a successfully validated pla-
cebo moxibustion method that could be used in a
double-blind RCT does not yet exist [17,18]. Thus, a
pragmatic design using a usual care group is appro-
priate for evaluating overall effectiveness in a moxi-
bustion trial [19].
More than half of Doctors of Korean Medicine (DKMs)
use moxibustion to treat KOA [20], and moxibustion is
one of the most common complementary and alternative
medicines in Korea [21]. Because of the wide prevalence
of moxibustion in Korea, it is necessary to evaluate the
economic worth of moxibustion for treating KOA, and a
qualitative study is needed in addition to the quantitative
approach to understand why KOA patients seek moxibus-
tion treatment and how they regard moxibustion treat-
ment performed by a DKM.
Our study will therefore take a pragmatic approach and
use a process of randomisation to assess the effectiveness
and safety of moxibustion for treating KOA compared to
usual care with a sample size calculated on the basis of a
previous pilot study. Moreover, an economic analysis will
be evaluated to assess the economic value of moxibustion
in Korea, and a qualitative study will be conducted to
understand the patient’s experience and perspective on
the use of moxibustion to treat KOA.
Methods/design
Objective
The aims of this study are as follows: (1) to assess the
effectiveness of moxibustion treatment for treating KOA
on the occurrence of pain, function, depression, quality
of life, and adverse events compared to usual care and
(2) to assess the cost-effectiveness and cost-utility of
moxibustion in addition to usual care in the treatment
of KOA patients and explore how KOA patients expe-
rience moxibustion in Korea.
Design and setting
This is a multicentre, pragmatic, randomised, assessor-
blinded, controlled, parallel-group study. From May
2011 to November 2011, 4 clinical research centres in
Korea will participate in this trial: the Korea Institute of
Oriental Medicine (Daejeon University Hospital) in
Daejeon, Gachon University Gil Oriental Medical Hos-
pital in Incheon, Dongshin University Gwangju Oriental
Hospital in Gwangju, and Semyung University Oriental
Medicine Hospital in Jecheon. The population of each
city is greater than 140,000, and the estimated preva-
lence rates of KOA are 14.9% over 40 years old [22] and
38.1% over 65 years old [23] in Korea. Recruitment will
therefore be expected to be completed within the study
period. To recruit the participants, we will advertise in
the media (daily papers, local newspapers, and public
newsletters), in each hospital, and on the internet
homepages of hospitals and public institutions. Eligible
participants will be randomly allocated into 2 groups
(the moxibustion group or the usual care group) with a
1:1 allocation ratio and receive treatment for 4 weeks
with 2 months of follow-up (Figure 1). The evaluation
of participants and the analysis of the results will be
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 2 of 9
http://www.biomedcentral.com/1472-6882/13/59
performed by professionals blinded to the group alloca-
tion. Written consent will be obtained from each par-
ticipant before the start of this trial. We will obtain oral
and written consent from each participant before
collecting information at the first visit.
Types of participants
Inclusion criteria
A total of 212 participants with KOA will be recruited
from the outpatients of the acupuncture and moxibustion
clinics of the 4 hospitals. We will include participants who
have average daily pain over 40 points (on a 0- to 100-
point scale) and have been diagnosed with idiopathic
KOA according to the clinical guidelines of the American
College of Rheumatology. The guidelines include patients
currently experiencing pain in one or both knees with at
least 3 of the following 6 conditions: 1) aged 50 to 70 years,
2) morning stiffness within 30 minutes of waking, 3) crepi-
tus, 4) bony tenderness, 5) bony enlargement, and 6) no
palpable warmth.
Exclusion criteria
Participants will be excluded if they are experiencing or
have a history of the following: inflammatory diseases,
including rheumatoid arthritis; cancer; traumatic injury
that might be related to the current knee pain; auto-
immune disease; uncontrolled hypertension; diabetes
mellitus requiring insulin injection; life-threatening car-
diovascular or neurological events within the past year;
chronic respiratory disease; a haemorrhagic disorder;
alcohol or drug addiction; an active infectious disease, in-
cluding tuberculosis; keloidosis; a significant knee joint
deformity; knee replacement surgery for the affected knee;
knee arthroscopy within the past 2 years; steroid injection
in the knee joints within the past 3 months; visco-
supplement injections in the knee joints within the past
6 months; joint fluid injection within the past 6 months;
and acupuncture, moxibustion, cupping, or herbal medi-
cine within the past 4 weeks.
Randomisation and allocation concealment
Randomisation will be performed using a computerised
random number generator through the stratified block
randomisation method of the SAS package (Version
9.1.3; SAS institute Inc., Cary, NC, USA) for sequence
generation prepared by a statistician (KWK) with no
clinical involvement in this trial. According to the
Kellgren/Lawrence Scale of anterior-posterior (AP) and
lateral standing knee radiographs, a random number will
be stratified using a random block size of 4. Sequentially
numbered, opaque, sealed assignment envelopes will be
delivered to each research centre. Random allocation
will be performed at the second visit for participants
who provide informed consent and meet the criteria for
inclusion. If a participant can be included in the study,
the researcher will open the corresponding envelope in
front of the participant. The corresponding envelopes
will be opened only after the enrolled participants have
completed all baseline assessments. Although partici-
pants and practitioners will be aware of the allocation
arm according to the routine care setting, the outcome
assessors and the data analysts will be kept blinded to
the allocation.
Intervention
Moxibustion treatment
Moxibustion treatment will be performed by DKMs who
are certified by the Korean Ministry of Health and Welfare.
They will have at least 2 years of clinical experience and
will have received more than 6 years of oriental medicine
college education. The treatment will be performed under
the supervision of professors who specialise in acupuncture
and moxibustion. All treatment regimens and outcome
assessment methods will be standardised between the 4
centres, and basic information about this study and the
monitoring process will be disseminated through work-
shops before the beginning of the study. This study is
designed to evaluate moxibustion treatment as it is used in
Figure 1 A flowchart of the study process.
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 3 of 9
http://www.biomedcentral.com/1472-6882/13/59
normal practice. The practitioner will therefore be allowed
to maintain a patient-practitioner relationship similar to a
normal clinical situation. There will be no restrictions in
the careful observation and questioning of participants.
In the moxibustion group, 3 moxibustion sessions per
week will be performed during a 4-week period for a
total of 12 sessions. The treatment will be conducted
after sterilising the skin surface at the acupuncture
points with the participant lying in a supine position at a
room temperature of 22°C to 28°C. After the top of the
moxibustion is sufficiently combusted without attach-
ment to the points for approximately 5 to 10 seconds,
the moxibustion will be attached at each point. When a
participant believes that their heat tolerance has reached
its maximum, the practitioners will place a new moxi-
bustion at the same point. However, to prevent burns,
the attached point can be changed to within a 1 cm
diameter according to the discretion of the practitioners.
A total of 3 moxibustions will be attached at each point at
every visit. We will use smokeless indirect moxibustions
made of mugwort with a paper cylinder (Manina, Haitnim
Co., Korea) (Figure 2). This moxibustion has an adhesive
on the bottom that can be used to attach it to the skin,
and its effect lasts approximately 5 to 10 minutes. The
expected total time of each treatment session will be 20 to
30 minutes. The treatment points were selected in a con-
sensus process by professors and researchers who have an
acupuncture and moxibustion specialist license in Korea
based on a text book [24], literature reviews [12,14,25],
and the points used in our previous pilot study. The moxi-
bustion group will receive moxibustion treatment on the
affected knee(s) at 6 standard acupuncture points (ST36,
ST35, ST34, SP9, Ex-LE04, and SP10) plus up to 2 points
of ‘ashi’, if needed, according to the determination of the
practitioners (Figure 3). The moxibustion group will also
receive the care provided to the usual care group.
Usual care
According to pragmatic design, the control group will not
use a placebo procedure. Both the moxibustion and usual
care groups will be allowed to use any type of treatment
desired, including surgery, conventional medication, phy-
sical treatment, acupuncture, herbal medicine, over-the
-counter drugs, and other active treatments. However, the
participants will be asked to inform the research investiga-
tors of any new treatments performed after entry into the
trial. Educational materials explaining KOA and self-
exercise will be provided to each group. The participants
in both groups will perform self-exercise, which consists
of 1) stretching the hamstrings, biceps femoris, and ankles
on both sides 3 times per day and 2) muscle exercises for
the hamstrings and biceps femoris (including isometric
and isotonic exercises) on both sides according to the dis-
ease status during the trial period.
Outcome
Primary outcome measurement
The primary outcome with respect to the effectiveness on
KOA will be the mean change in the global scale value of
the Western Ontario and McMaster Osteoarthritis Index
(WOMAC) from baseline to 5 weeks. The WOMAC is
Figure 2 Moxibustion device. A photograph of the moxibustion
device that will be used in this trial. This moxibustion device is a
sticker-type disposable moxa, which functions for 5–10 minutes and
is used for local acupuncture points. M: the upper part of the
carbonised mugwort, A: adhesive sticker, H: height (2.1 cm), D:
distance (1.9 cm).
Figure 3 Acupuncture points of treatment. The right knee will be
treated at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-
LE04, and SP10). The left knee will be treated with an additional
point of ‘ashi’, which is located between ST35 and Ex-LE04. A:
additional points of ‘ashi’according to the determination of the
practitioner. A Written consent for the picture was obtained from
the pictured subject. Photograph by Seunghoon Lee.
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 4 of 9
http://www.biomedcentral.com/1472-6882/13/59
one of the most widely used instruments and is composed
of 24 questions to assess disability related to osteoarthritis.
It includes 3 subscales to measure pain (5 questions), stiff-
ness (2 questions), and physical function (17 questions) in
KOA, and higher scores indicate more severe impairment
[26,27]. There is a Korean version of the WOMAC
(K-WOMAC), and Bae et al. confirmed its reliability, va-
lidity, and responsiveness [28]. We will therefore assess
participants at the second visit (before starting moxibus-
tion treatment) and at 5 weeks and 13 weeks from base-
line using the K-WOMAC.
Secondary outcome measurements
Secondary outcomes include the mean changes in the
WOMAC subscales (pain, stiffness, and function) at 5
and 13 weeks from baseline. As such, we will investigate
which subscales affect the global scale value of the
WOMAC, which is the primary outcome measurement.
Health-related quality of life (HRQL) will be assessed
by the Short-Form 36v2 Health Survey (SF-36) at 5 and
13 weeks from baseline. The SF-36 is used to measure
the general health status and quality of life of patients
and non-patients. It comprises a total of 36 questions in
8 categories, and higher scores indicate a better level of
function. Han et al. developed a Korean version of the
SF-36 and assessed its reliability and validity for use in
health-related quality of life measurements for elderly
Korean patients [29].
Depression will be assessed by a mean change in Beck
Depression Inventory (BDI) scores at 5 and 13 weeks
from baseline. The BDI, developed by Beck AT in 1967,
is a 21-question multiple-choice questionnaire that is
one of the most widely used scales for measuring the se-
verity of depression. It is composed of items related to
the depression symptoms of hopelessness and irritability,
cognition (such as guilt and feelings of being punished),
and physical symptoms (such as fatigue and weight loss);
higher total scores indicate more severe depressive
symptoms [30].
To assess physical activity, a physical performance test
will be performed at 5 and 13 weeks from baseline. The
physical performance test is composed of the timed
stand, standing balance, and 6-minute walk tests. 1) The
timed stand test evaluates lower extremity muscle power
by measuring the time required to complete 10 full
stands from a sitting position. 2) The standing balance
test assesses balance in particular positions, such as tan-
dem, semi-tandem, side-by side, and one-legged stands.
3) The 6-minute walk test measures the distance walked
at the greatest speed possible within 6 minutes to assess
the functional exercise capacity of patients [31].
Global knee pain will be assessed using the patient
global assessment and numerical rating scale (NRS). The
patient global assessment score is a self-reported 5-point
measurement used to evaluate overall improvement after
treatment. Participants individually evaluate their im-
provement from baseline by selecting one of 5 options
(much improved, minimally improved, no change, mi-
nimally worse, or much worse) at 5 and 13 weeks from
baseline. The pain NRS (0 = no pain and 10 = worst po-
ssible pain) is a standard instrument in chronic pain
studies that is used to measure pain intensity [32]. We
will evaluate the mean change in the NRS within 7 days
of the study visits at 5 and 13 weeks from baseline.
The treatment expectancy of participants will be evalu-
ated by the Treatment Expectancy Questionnaire (1 = not
at all, 5 = somewhat and 9 = very much), which has been
transformed and translated into Korean from the “Cre-
dibility and Expectancy Questionnaire”[33]. Participants
will be asked “How much do you feel moxibustion therapy
will help to reduce your symptoms?”at the first visit.
A blood sample will be obtained at baseline and 5 weeks
from baseline to measure the C-reactive protein (CRP)
levels and the erythrocyte sedimentation rate (ESR). We
will therefore evaluate inflammation and tissue damage
after moxibustion treatment. The detailed outcome meas-
urement time points are provided in Table 1.
Sample size
We calculated the sample size according to our previous
pilot study. A 2-sided 5% significance level and 80% power
were considered to detect a mean difference in the
WOMAC of −6.65 with a standard deviation (SD) of 15.4.
Approximately 84 participants in each group were calcu-
lated to be required. Assuming a dropout rate of 20%, the
sample size will be n = 106 for each group (total n = 212).
A total of 32 participants will be assigned at the Korea
Institute of Oriental Medicine (Daejeon University Hos-
pital), and the remaining 180 participants will be equally
assigned at the other 3 study hospitals. To recruit this
number of participants, a 6-month study period is antici-
pated based on our pilot study.
Statistical analysis
The statistical analysis will be performed on the intention-
to-treat basis with a 95% confidence interval using SAS
(Version 9.1.3; SAS institute Inc., Cary, NC, USA). Mis-
sing data will be replaced according to the principle of the
last observation carried forward (LOCF) method. The null
hypothesis is that there will be no difference in the change
in the primary outcome between the moxibustion group
and the usual care group after 5 weeks of treatment. The
baseline characteristics will be shown as the mean ± SD
for continuous data (e.g., age and duration of disease)
and n (%) for categorical data (e.g., gender and Kellgren/
Lawrence Scale).
To analyse the baseline characteristics, we will per-
form a 2-sample t-test or a Wilcoxon rank sum test for
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 5 of 9
http://www.biomedcentral.com/1472-6882/13/59
continuous data and a chi-squared test or Fisher’s exact
test for categorical data, according to whether the data
are normally distributed. An analysis of covariance
(ANCOVA) will be performed for the primary endpoint
(global scale value of WOMAC) and secondary end-
points (WOMAC subscales (pain, stiffness, and func-
tion), HRQL, depression, physical activity, and patient
global assessment) at 5 weeks and 13 weeks from base-
line. The ANCOVA model will include group as a fixed
effect and baseline measurements and centres as covari-
ates. The mean difference from baseline values to the
end of treatment in each group will be examined using a
paired t-test or a Wilcoxon signed rank test. To identify
a trend, we will also perform a repeated measures ana-
lysis of variance.
Additional analyses
Economic evaluation
The economic evaluation will be conducted from a so-
cial perspective, and all costs and consequences of the
competing interventions will be considered regardless of
who pays for or benefits from them. All cost data will be
collected through a cost questionnaire that participants
will complete at 5 weeks and 13 weeks after baseline.
Researchers will explain these to all of the participants,
and obtain the consent before collecting economic data.
The costs considered in the present analysis will include
the direct healthcare-related costs of moxibustion treat-
ment, physician visits, hospital stays (without conside-
ration of private billings), and any drugs (including
patient co-payments). In addition to health insurance
costs, the indirect costs caused by lost workdays will also
be taken into account. Health utility will be measured in
quality-adjusted life years calculated for each patient
using the SF-36 at 5 weeks and 13 weeks after baseline,
and the K-WOMAC pain subscale will also be used to
analyse cost-effectiveness. The cost-utility and cost-
effectiveness analyses will be performed through a deci-
sion analysis. The analysis period will be 5 weeks, and
the trend will also be evaluated at 13 weeks.
Qualitative research
We will also conduct a qualitative study based on the
grounded theory to elucidate the meaning of the experi-
ences of moxibustion treatment for KOA. Sixteen KOA
patients who will be selected by convenience sampling will
Table 1 Schedule for treatment and outcome measurements
Period S T F
Visit 1 23456789101112131415
Week 11122233 3 4 4 4 513
Informed Consent ●
Demographic Characteristics ●
Medical History ●
Knee X-Ray ●
Inclusion/Exclusion Criteria ●
Conformity Assessment ●
Treatment Expectancy Questionnaire ●
Blood Test ● ●
Vital Signs ●●○○○○○○○ ○ ○ ○ ○ ●●
Change in Medical History ●○○○○○○○ ○ ○ ○ ○ ●●
Random Allocation ●
Moxibustion Treatment ○○○○○○○○ ○ ○ ○ ○
K-WOMAC ●●●
Beck Depression Inventory ●●●
The Short-Form 36v2 Health Survey ●●●
Pain Numerical Rating Scale ●● ●●
Physical Function Test ●●●
Patient Global Assessment ●●●
Safety Assessment ●○○○○○○○ ○ ○ ○ ○ ●●
S: Screening Period, T: Treatment Period, F: Follow-up Period, K-WOMAC: Korean Western Ontario and McMaster Osteoarthritis Index, ●: Both the moxibustion
group and the usual care group, ○: Only the moxibustion group.
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 6 of 9
http://www.biomedcentral.com/1472-6882/13/59
be included in the qualitative study if they consent to give
a recorded face-to-face interview. We will conduct individ-
ual in-depth interviews using open-ended questions at a
site where they feel comfortable. The interviewer will ask
the participants the key question, “Tell me about your ex-
periences with obtain moxibustion treatment for treating
KOA”, and additional questions, such as “What is the most
difficult activity due to KOA?”,“Whydidyouchoosemoxi-
bustion treatment? What was your motivation?”,“What
was your expectation when you participated?”,“What types
of changes did you feel after you received moxibustion?
Were there any symptom changes after moxibustion treat-
ment?”,“Did you have any difficulties or problems during
the moxibustion treatment? What did you do to overcome
these troubles?”,“Will you choose moxibustion treatment
again when you have a similar or other symptom?”,and
“Will you recommend moxibustion treatment to others?”.
Thedatawillbetranscribedfromtherecordingand
analysed using the coding scheme, and researchers will
then categorise them according to the process for qualita-
tive research methods.
Data and safety monitoring
Regular monitoring that will be clarified in a standard
operating procedure will be conducted at each site to
ensure good data quality. Monitors will evaluate whether
the case report forms are properly written and whether
the recruiting and treatment procedures are adequately
performed according to the protocol. Investigators from
each site will be contacted to discuss whether it is neces-
sary to revise the study protocol or inclusion criteria and
other important issues. The investigators and independ-
ent researchers will assess the progress of the clinical
trial and severe adverse events and determine whether
they are acceptable and whether it will be necessary for
the trial to be modified or stopped.
Adverse events
All unexpected and unintended responses that are not ne-
cessarily related to moxibustion treatment will be reported
by the participants and practitioners at every visit. The
adverse events known to occur following moxibustion
treatment include blisters, redness, itching, burns, and
respiratory symptoms. To avoid potential adverse events,
the treatment day will be modulated within 3 days if the
practitioner judges that the participant is not suitable for
moxibustion treatment or the participant indicates mode-
rate fatigue or an abnormal health condition.
Participant protections and ethics
To protect human participants, the protocol was written
according to general ethical guidelines, such as the Decla-
ration of Helsinki and Korean Good Clinical Practice and
was approved by the institutional review board of each
trial centre (Daejeon University Hospital, Kyungwon
University Gil Oriental Medical Hospital, Dongshin Uni-
versity Gwangju Oriental Hospital, and Semyung Univer-
sity Oriental Medicine Hospital). The Korea Institute of
Oriental Medicine certified the ethics approval of the cli-
nical centres as above. The study participant consent
process includes information about potential risks, bene-
fits, alternatives, and responsibilities during the trial. Before
participants agree to participate in this trial, researchers
will explain this information in detail in person.
Discussion
Moxibustion and acupuncture have been widely used to
treat the pain and functional limitations of KOA in Korea
[20]. Some trials [11-14,34] have been conducted to eva-
luate the effectiveness of moxibustion in treating KOA in
Korea and China. Moxibustion and NSAIDs were com-
pared in 3 RCTs [11-13], combination therapy (moxibus-
tion plus NSAIDs) and NSAIDs were compared in 1 RCT
[14], and moxibustion and a hot pack were compared in 1
RCT [34]. According to these trials, single or combination
moxibustion therapies increased the total response rate
and decreased symptoms of pain in KOA patients. How-
ever, the processes of random sequence generation and
allocation concealment were not reported in 4 trials
[11,13,14,34]. Moreover, none of the trials used valid and
reliable assessment tools, such as the WOMAC, and asses-
sor blinding was not described. It is therefore not possible
to exclude the possibility of a high risk of bias and deter-
mine the effectiveness of moxibustion treatment for KOA.
Concealment is the most critical factor of the alloca-
tion process, and a high risk of bias is generated by un-
concealed allocation [35,36]. In a recent well-designed
systematic review of acupuncture for chronic pain, only
RCTs that used an unambiguous method of allocation
concealment were included [37]. Therefore, we designed
our protocol with adequate methodology of random se-
quence generation and allocation concealment using val-
idated assessment tools, such as the WOMAC, SF-36,
and BDI, and monitors will regularly evaluate whether
the trial is being conducted according to the planned
protocol.
Mixed-method research is the most recent systematic
approach of using 2 or more research methods to answer
a single research question. This approach has the advan-
tages of expanding the understanding of the procedure's
effects and verifying results from another perspective
compared to an approach using a single method because
the supplemental component enhances the validity of the
study [36,38]. This method has been used to determine
the effectiveness of interventions in recent studies on
complementary and alternative medicine [39-41]. To com-
prehensively understand the effectiveness of moxibustion
for KOA patients, we will conduct not only a quantitative
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 7 of 9
http://www.biomedcentral.com/1472-6882/13/59
data analysis but also economic and qualitative data ana-
lyses. A nested economic evaluation and qualitative re-
search within a pragmatic clinical trial will be used as a
mixed-methods approach to answer the question from
various perspective on the reasons for using moxibustion
for KOA.
One limitation of this study is the possibility of a high
risk of bias regarding blinding because we will use usual
care as a control instead of a sham procedure. One study
[42] on functional constipation used sham moxibustion to
blind participants to evaluate the efficacy of moxibustion,
but a blinding test was not performed, and it is necessary
to cover the eyes with a patch to successfully blind parti-
cipants to the sham moxibustion device [43]. The re-
searchers who designed this protocol agreed that it would
be difficult to blind participants using any previously de-
veloped sham device [17,43,44], and that a sham device is
difficult to use because of the high prevalence of moxibus-
tion in Korea and there are technical challenges associated
with developing a sham device. Additionally, it is more
appropriate to use a pragmatic design to answer our re-
search question, which is whether moxibustion treatment
is effective in treating KOA in real practice. Therefore, we
used the pragmatic approach of comparing treatment to
usual care, permitting additional treatment points as well
as standard treatment points, and using patient-centred
outcomes in multiple centres.
This pragmatic randomised controlled trial using the
mixed-methods approach may provide rigorous evidence
for the effectiveness of moxibustion in treating KOA.
Competing interests
The authors declare that they have no competing interests.
Authors’contributions
SL wrote the study protocol and drafted this manuscript. KHK made a
substantial contribution to designing the study protocol. THK participated in
the study design of the qualitative study and in critical revision. JEK, JHK, and
JWK participated in the critical revision of the manuscript. KWK participated
in the design of the statistical analysis and the cost-effectiveness analysis.
SYJ, ARK, HJP, and MSS participated in the design of the outcome
measurements and assessing the outcomes. KEH, HSS, JBC, and HJK helped
to draft the manuscript. SMC had final responsibility for the decision to
submit for publication. All of the authors read and approved the final
manuscript.
Acknowledgements
This study is supported by the Development of Acupuncture, Moxibustion
and Meridian Standard Health Technology (K11010) of the Korea Institute of
Oriental Medicine.
Author details
1
Acupuncture, Moxibustion & Meridian Research Group, Medical Research
Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.
2
Department of Acupuncture & Moxibustion, College of Korean Medicine,
Kyung Hee University, Seoul, South Korea.
3
Department of Acupuncture &
Moxibustion Medicine, Korean Medicine Hospital, Pusan National University,
Pusan, South Korea.
4
Mokhuri Neck and Back Hospital, Seoul, South Korea.
5
Department of Acupuncture & Moxibustion, College of Oriental Medicine,
Daejeon University, Daejeon, South Korea.
6
Department of Acupuncture &
Moxibustion, College of Oriental Medicine, Gachon University, Incheon,
South Korea.
7
Department of Oriental Rehabilitation Medicine, College of
Oriental Medicine, Dong-Shin University, Gwangju, South Korea.
8
Department
of Oriental Gynaecology, College of Oriental Medicine, Se-Myung University,
Jecheon, South Korea.
Received: 24 August 2012 Accepted: 28 February 2013
Published: 13 March 2013
References
1. National Collaborating Centre for Chronic Condition: Osteoarthritis: national
clinical guideline for care and management in adults. London: Royal College
of Physicians; 2008.
2. Altman R, Brandt K, Hochberg M, Moskowitz R, Bellamy N, Bloch DA,
Buckwalter J, Dougados M, Ehrlich G, Lequesne M, Lohmander S, Murphy
WA Jr, Rosario-Jansen T, Schwartz B, Trippel S: Design and conduct of
clinical trials in patients with osteoarthritis: recommendations from a
task force of the osteoarthritis research society. Results from a
workshop. Osteoarthr Cartil 1996, 4(4):217–243.
3. Peat G, McCarney R, Croft P: Knee pain and osteoarthritis in older adults:
a review of community burden and current use of primary health care.
Ann Rheum Dis 2001, 60(2):91–97.
4. Bjordal JM, Ljunggren AE, Klovning A, Slordal L: Non-steroidal anti-
inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in
osteoarthritic knee pain: meta-analysis of randomised placebo controlled
trials. BMJ 2004, 329(7478):1317.
5. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G:
Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006,
25(1):CD004257.
6. Kwon YD, Pittler MH, Ernst E: Acupuncture for peripheral joint
osteoarthritis: a systematic review and meta-analysis. Rheumatology
(Oxford) 2006, 45(11):1331–1337.
7. World Health Organization: WHO international standard terminologies on
traditional medicine in the western pacific region. Manila: World Health
Organization, Western Pacific Region; 2007.
8. Lee J, Lee C, Song T, Hanguk Hanuihak Y: Introduction to traditional Korean
medicine. Daegeon: Korea Institute of Oriental Medicine; 2008.
9. Manheimer E, Cheng K, Linde K, Lao L, Yoo J, Wieland S, van der Windt DA,
Berman BM, Bouter LM: Acupuncture for peripheral joint osteoarthritis.
Cochrane Database Syst Rev 2010, 20(1):CD001977.
10. Choi TY, Kim TH, Kang JW, Lee MS, Ernst E: Moxibustion for rheumatic
conditions: a systematic review and meta-analysis. Clin Rheumatol 2011,
30(7):937–945.
11. Cheng H, Han W, Hu P, Yang J: Clinical study of differential selecton of
objects separated moxibustion for treatment of knee osteoarthritis.
Clin J Tradit Chin Med 2008, 20:114–116.
12. Sun K, Yang J, Shen DK: Clinical observation on treatment of primary
knee osteoarthritis of liver and kidney deficiency type with aconite
cake-separated moxibustion. Zhongguo zhen jiu 2008, 28(2):87–90.
13. Yang Y, Sun K, Su G, Zhou C: Clinical study panax notoginsengs cake
separated moxibustion treatment of qi stagnation blood stasis type for
primary knee osteoarthritis 37 cases. Clin J Tradit Chin Med 2008, 20:53–55.
14. He Y, Xu Y, Huo X: Clinical research of moxibustion in treating knee joint
osteoarthritis. Herbei J Tradit Chin Med 2009, 22:28–30.
15. Schulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines
for reporting parallel group randomised trials. BMC medicine 2010, 8:18.
16. 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. J Altern
Complement Med 2010, 16(10):ST1–ST14.
17. Zhao B, Wang X, Lin Z, Liu R, Lao L: A novel sham moxibustion device: a
randomized, placebo-controlled trial. Complementary therapies in medicine
2006, 14(1):53–60.
18. Kim SY, Chae Y, Lee SM, Lee H, Park HJ: The effectiveness of moxibustion:
an overview during 10 years. Evid Based Complement Alternat Med 2009.
Epub 2011 Jun 23:306515.
19. Macpherson H: Pragmatic clinical trials. Complement Ther Med 2004,
12(2–3):136–140.
20. Lee YR, Kim EJ, Cho HS, Lee SD, Kim KS, Kim KH: Interview survey methods
for moxibustion treatment of knee pain, neck pain and back pain:
subject to oriental doctors in Seoul. J Korean Acupunct Moxibustion Soc
2011, 28(2):1–11.
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 8 of 9
http://www.biomedcentral.com/1472-6882/13/59
21. Kim HA, Seo YI: Use of complementary and alternative medicine by
arthritis patients in a university hospital clinic serving rheumatology
patients in Korea. Rheumatol Int 2003, 23(6):277–281.
22. Cho NH, Kim S, Kim HA, Seo YI: The prevalence and risk factors of knee and
hand osteoarthritis in Korea. J Korean Rheum Assoc 2007, 14(4):354–362.
23. Cho HJ, Chang CB, Jung JW, Seong SC, Kim TK: Prevalence of radiographic
knee osteoarthritis in elderly Koreans. J Korean Knee Soc 2009,
21(4):223–231.
24. Text book committee of Korean Acupuncture & Moxibustion Society: The
acupuncture and moxibustion, volume 3. 2nd edition. Paju: Jipmoondang;
2008:118–124.
25. Park JS, Kwon SJ, Kwon YS: The effects of dogbi(ST35) & sulan
moxibustion on knee joint pain, range of motion and discomfort during
ADL in the aged. J Korean Acad Nurs 2006, 36(1):189–196.
26. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW: Validation study
of WOMAC: a health status instrument for measuring clinically important
patient relevant outcomes to antirheumatic drug therapy in patients with
osteoarthritis of the hip or knee. J Rheumatol 1988, 15(12):1833–1840.
27. Wolfe F: Determinants of WOMAC function, pain and stiffness scores:
evidence for the role of low back pain, symptom counts, fatigue and
depression in osteoarthritis, rheumatoid arthritis and fibromyalgia.
Rheumatology (Oxford) 1999, 38(4):355–361.
28. Bae SC, Lee HS, Yun HR, Kim TH, Yoo DH, Kim SY: Cross-cultural adaptation
and validation of Korean western Ontario and McMaster universities
(WOMAC) and lequesne osteoarthritis indices for clinical research.
Osteoarthr Cartil 2001, 9(8):746–750.
29. Han CW, Lee EJ, Iwaya T, Kataoka H, Kohzuki M: Development of the
Korean version of short-form 36-item health survey: health related QOL
of healthy elderly people and elderly patients in Korea. Tohoku J Exp Med
2004, 203(3):189–194.
30. Beck AT: Depression; causes and treatment. Philadelphia: University of
Pennsylvania Press; 2006.
31. Wang C, Schmid CH, Hibberd PL, Kalish R, Roubenoff R, Rones R, Okparavero A,
McAlindon T: Tai Chi for treating knee osteoarthritis: designing a long-term
follow up randomized controlled trial. BMC Musculoskelet Dis 2008, 9:108.
32. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM: Clinical
importance of changes in chronic pain intensity measured on an
11-point numerical pain rating scale. Pain 2001, 94(2):149–158.
33. Devilly GJ, Borkovec TD: Psychometric properties of the credibility/
expectancy questionnaire. J Behav Ther Exp Psychiatry 2000, 31(2):73–86.
34. Doh MH, Kim TY: Effects of the moxibustion therapy on the pain
decrease and joint recovery with degenerative knee arthritis. Korean J
Orient Prevent Med 2009, 13(1):88–92.
35. Schulz KF, Chalmers I, Hayes RJ, Altman DG: Empirical evidence of bias.
Dimensions of methodological quality associated with estimates of treatment
effects in controlled trials. JAMA 1995, 273(5):408–412.
36. Witt CM, Linde K: Clinical research in complementary and integrative medicine:
a practical training book. 1st edition. Munich: Elsevier; 2011:147–152.
37. Vickers AJ, Cronin AM, Maschino AC, Lewith G, Macpherson H, Foster NE,
Sherman KJ, Witt CM, Linde K, for the Acupuncture Trialists C: Acupuncture
for chronic pain: individual patient data meta-analysis. Arch Intern Med
2012, 172(19):1444–1453.
38. Morse JM, Niehaus L: Mixed method design. Walnut Creek, California: Left
Coast Press; 2009:13–22.
39. Kim TH, Kang JW, Kim KH, Kang KW, Shin MS, Jung SY, Kim AR, Jung HJ, Lee
SD, Choi JB, et al: Acupuncture for dry eye: a multicentre randomised
controlled trial with active comparison intervention (artificial tear drop)
using a mixed method approach protocol. Trials 2010, 11:107.
40. White P, Bishop FL, Prescott P, Scott C, Little P, Lewith G: Practice,
practitioner, or placebo? a multifactorial, mixed-methods randomized
controlled trial of acupuncture. Pain 2012, 153(2):455–462.
41. DeBar LL, Elder C, Ritenbaugh C, Aickin M, Deyo R, Meenan R, Dickerson J,
Webster JA, Jo Yarborough B: Acupuncture and chiropractic care for
chronic pain in an integrated health plan: a mixed methods study. BMC
Comp Alt Med 2011, 11:118.
42. Park JE, Sul JU, Kang K, Shin BC, Hong KE, Choi SM: The effectiveness of
moxibustion for the treatment of functional constipation: a randomized, sham-
controlled, patient blinded, pilot clinical trial. BMC Comp Alt Med 2011, 11:124.
43. Park JE, Han CH, Kang KW, Shin MS, Oh DS, Choi SM: A sham moxibustion
device and masking test. J Korean Orient Med 2007, 13:93–100.
44. Kim SY, Yi SH, Cho JH, Yin CS, Lee H, Park HJ: Heat stimulation on the skin
for medical treatment: can it be controlled? J Altern Complement Med
2011, 17(6):497–504.
doi:10.1186/1472-6882-13-59
Cite this article as: Lee et al.:Moxibustion for treating knee
osteoarthritis: study protocol of a multicentre randomised controlled
trial. BMC Complementary and Alternative Medicine 2013 13:59.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at
www.biomedcentral.com/submit
Lee et al. BMC Complementary and Alternative Medicine 2013, 13:59 Page 9 of 9
http://www.biomedcentral.com/1472-6882/13/59
