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Efficacy and safety of ginger-salt-
indirect moxibustion for urge urinary
incontinence after stroke: protocol
for a pilot multicentre randomised
controlled trial
Linpeng Wang,
1
Lichen Wang,
1
Guangxia Shi,
1
Lin Zeng,
2
Yi Yang,
1
Tao Zhang,
1
Huilin Liu
1
To cite: Wang L, Wang L,
Shi G, et al. Efficacy and
safety of ginger-salt-indirect
moxibustion for urge urinary
incontinence after stroke:
protocol for a pilot
multicentre randomised
controlled trial. BMJ Open
2014;4:e006326.
doi:10.1136/bmjopen-2014-
006326
▸Prepublication history for
this paper is available online.
To view these files please
visit the journal online
(http://dx.doi.org/10.1136/
bmjopen-2014-006326).
Received 7 August 2014
Revised 19 September 2014
Accepted 24 September 2014
1
Acupuncture and
Moxibustion Department,
Beijing Hospital of Traditional
Chinese Medicine affiliated to
Capital Medical University,
Beijing, China
2
Research Center of Clinical
Epidemiology Affiliated to
Peking University, Beijing,
China
Correspondence to
Dr Huilin Liu;
lhlxwy@aliyun.com
ABSTRACT
Introduction: Ginger-salt-indirect moxibustion is
widely applied to treat urge urinary incontinence after
stroke, which is a common complication in stroke
survivors. Moxa cone moxibustion and moxa box
moxibustion are the main techniques of ginger-salt-
indirect moxibustion. Our previous study had shown
that ginger-salt-indirect moxibustion using moxa cones
was feasible and effective for urination disorders post-
stroke. This pilot study aims to assess the feasibility of
conducting research to evaluate the efficacy and safety
of ginger-salt-indirect moxibustion for patients with
post-stroke urge urinary incontinence.
Methods and analysis: This is a multicentre,
prospective, single-blinded, pilot randomised controlled
trial. 120 eligible patients will be randomly allocated to
three groups. Treatment group A (n=40) will receive
moxa cone moxibustion and routine care; treatment
group B (n=40) will receive moxa box moxibustion and
routine care; control group (n=40) will only receive
routine care for stroke recovery. The entire moxibustion
treatment will consist of a total of 28 sessions during
the course of 4 weeks. The primary outcome measure
will be the increase in mean volume per void assessed
at week 4 from the first moxibustion session
(baseline). Secondary outcome measures will include
mean frequency of urination per day and quality of life
assessments measured by completion of the
Incontinence Quality of Life Questionnaire and Barthel
Index. All outcome measures will be assessed at
baseline and at 4 and 16 weeks from baseline. Adverse
events in the three groups will be recorded to assess
the safety of moxibustion.
Ethics and dissemination: Research ethics was
approved by the Research Ethical Committee of Beijing
Hospital of Traditional Chinese Medicine Affiliated to
the Capital Medical University (ref: 2013BL-094).
Written informed consent will be obtained from all
participants. Study results will be published in peer
reviewed journals.
Trial registration number: ISRCTN 44706974.
INTRODUCTION
Urinary incontinence (UI) is defined by the
International Continence Society (ICS) as
involuntary leakage of urine that causes
hygienic or social problems.
1
The prevalence
of UI after stroke varies from 32–79% at
admission,
2–4
25% at hospital discharge, and
15% after 1 year.
4
Urge urinary incontinence
(UUI) is a common type of UI
5
that occurs
after stroke. It is characterised by involuntary
leakage of urine accompanied or preceded
by urgency.
1
The results of a previous review
6
suggested
that there were three major causes of UI
after stroke: detrusor hyperreflexia caused by
infarction; stroke-related cognitive or lan-
guage deficits; and bladder hyporeflexia with
resultant overflow incontinence. UUI can be
caused by detrusor overactivity due to the
loss of inhibitory neurones after stroke.
7
Detrusor overactivity is characterised by invol-
untary detrusor contractions during the
filling and storage phase.
178
When intra-
detrusor pressure generated by abnormal
Strengths and limitations of this study
▪First pilot study to evaluate the feasibility of con-
ducting research to assess the efficacy and
safety of ginger-salt-indirect moxibustion as
treatment for urge urinary incontinence after
stroke.
▪Multicentre, randomised controlled trial with
pragmatic design.
▪Interventions conducted by certified acupunctur-
ists according to the STRICTOM and good clin-
ical practice guidelines (GCP).
▪Lack of blinding of acupuncturists and partici-
pants due to the nature of moxibustion.
Wang L, et al.BMJ Open 2014;4:e006326. doi:10.1136/bmjopen-2014-006326 1
Open Access Protocol
detrusor contractions exceeds sphincter pressure, UI
occurs.
7
UI is a strong prognostic indicator for stroke
recovery, which is associated with high rates of mortal-
ity,
910
disability
11
and increasing admission to institu-
tional care.
12
Micturition disorders may result in urinary
infection, nephritis, fungal dermatitis,
13
and even bed-
sores. Typical symptoms, including frequent micturition,
nocturia and urgency, could lead to impaired quality of
life
14
and heavy economic burden.
15 16
Initial treatments for UUI after stroke recommended
by ICS are behavioural therapy and pharmacotherapy.
1
Behavioural therapies, including healthy bladder habits
and training techniques, are aimed at changing patient
lifestyle and at teaching patients to control urgency and
enhance continence ability.
17
For habit modification,
patients are given guidance on how to re-establish a
healthy voiding schedule, eliminate bladder irritants
from the diet, manage fluid intake and bowel regularity,
control weight, and give up smoking.
18–24
Training tech-
niques consist of bladder training, urgency control tech-
niques, pelvic muscle exercises, delayed voiding, and
multicomponent behavioural training.
17
Behavioural
interventions are applied in the primary care setting,
with or without pharmacotherapy.
25–27
Among these
strategies, behavioural training and bladder training
have the strongest evidence of efficacy for the treatment
of UUI.
28–31
Antimuscarinic drugs can reduce urgency and
improve bladder function by controlling detrusor
muscle overactivity through inhibition of M2 and M3
muscarinic bladder receptors.
32–34
Several meta-analyses
have shown that the most widely used antimuscarinic
drugs have significant clinical benefits on UUI.
35–38
However, use of antimuscarinic agents is complicated by
dose convenience, drug contraindication, and financial
concerns.
39
A Cochrane systematic review
40
concluded
that no studies designed to manage UI after stroke in
secondary care had been rigorously conducted so far.
Although there are clinical guidelines for the manage-
ment of UI after stroke,
1
to date there is insufficient
good quality evidence to support current clinical prac-
tices.
41
More available therapies and well-designed
studies are required to provide further evidence for
management of UUI after stroke.
Moxibustion is a therapy that uses ignited materials
(usually moxa) to heat selected points of the skin
surface. This therapy is widely used for chronic defi-
ciency diseases
42
and is commonly indicated for UUI.
43
The mechanism of action of moxibustion combines
thermal, radiation and pharmacological effects of the
materials used, acting on the meridian system.
44
Following the theory of Traditional Chinese Medicine
(TCM), kidney qi regulates voiding function and ensures
voluntary urination. Deficiency of kidney qi is known to
be the primary pathogenesis of UI according to
‘ZhuBingYuanHouLun’(a famous ancient TCM litera-
ture). Ginger and salt are typically used on Shenque
(CV8) acupoint to warm, tonify and nourish the kidney
qi, thereby controlling the bladder and regulating
voiding function.
Moxa cone moxibustion and moxa box moxibustion
are primary techniques of ginger-salt-indirect moxibus-
tion, which are commonly used in clinical practices in
China. Moxa cone moxibustion involves a moxa cone
burning directly on the ginger slice and providing
thermal stimulus to the skin surface. Moxa box moxibus-
tion facilitates manipulations and reduces adverse reac-
tions by using the moxa box device with moxa sticks
inside over the ginger slice. Results of our previous
study
45
showed that ginger-salt-partitioned moxibustion
with moxa cone could reduce mean daytime and night-
time voiding frequency in the treatment of urination dis-
orders post-stroke. In addition, we also observed that
ginger-salt-indirect moxibustion with moxa cones could
increase mean volume per void of UI after stroke in an
unpublished study. Our previous studies, together with
results from an earlier Cochrane review,
40 45
suggest
ginger-salt-indirect moxibustion may be worth investigat-
ing with more rigorous study design.
METHODS
Objectives
This pilot study aims to evaluate the feasibility of research
to assess the efficacy and safety of ginger-salt-indirect
moxibustion for the treatment of UUI after stroke.
Recruitment
This is a multicentre, single-blinded, pilot randomised
controlled trial. The research consists of three sequential
parts (figure 1): a recruitment period before randomisa-
tion, a treatment period of 4 weeks, and a follow-up
period of 12 weeks. One hundred and twenty eligible
participants will be recruited from acupuncture wards of
three hospitals according to the inclusion and exclusion
criteria. During the first visit, potentially qualified
patients will be provided with detailed information
about this study, including the research objective, study
procedure, potential benefits and risks. If a patient
shows willingness to participate, they will be required to
voluntarily sign a written informed consent. This will be
followed by baseline assessment and randomisation.
Design
Randomisation and allocation concealment
The randomisation scheme is provided by the Research
Center of Clinical Epidemiology Affiliated to Peking
University Third Hospital in China. Statistical experts
will use the block randomisation method (block size of
6) of the SAS package (V.9.1.3; SAS institute Inc, Cary,
North Carolina, USA) to form the random allocation
sequence. Then computer-generated opaque sealed
envelopes, each with the serial number outside and
group number inside, will be produced. The envelopes
will be kept in a secure locked drawer making it inaccess-
ible to all study personnel. After baseline assessments,
2Wang L, et al.BMJ Open 2014;4:e006326. doi:10.1136/bmjopen-2014-006326
Open Access
the envelopes will be opened sequentially by an inde-
pendent researcher in front of the participants to
ensure adequate concealment. Participants will be allo-
cated to three groups according to the group number
printed inside the envelopes.
Blinding
Due to the nature of moxibustion, it is difficult to
ensure the therapists or participants are blinded to the
treatment allocation. Data managers and statisticians will
be blinded throughout the trial. During the interven-
tion, therapists and data managers will be requested not
to communicate with each other about the allocation.
Blinded telephone interviewers will collect the follow-up
materials to evaluate the long term effect of moxibustion
at 16 weeks after the baseline.
Participants
Sample size
Because this is a pilot study, a power calculation to deter-
mine the sample size was not conducted. Sample size
calculation was performed based on estimates of the
number of participants we would expect to recruit
within 24 months. We therefore plan to recruit five parti-
cipants per month, according to our previous trial. A
sample size of 40 per group and a total number of 120
will be included, which is larger than the minimum of
12 per group suggested for pilot studies.
46
Outcomes of
this pilot study will help calculate the appropriate
sample size for further randomised clinical trials.
Inclusion criteria
1. Male or female, aged 40–75 years
2. Inpatients with UUI after stroke, according to the
diagnosis criteria of the American Stroke Association
and the ICS
3. 4th to 48th week after stroke onset
4. Normal consciousness, communication ability and
recognition
5. Written informed consent.
Exclusion criteria
1. UUI caused by spinal injury, multiple sclerosis or
hyperplasia of the prostate gland
2. Chronic urinary retention or UI before stroke onset
3. Stress UI, mixed UI and chronic urinary tract infection
4. Insufficiency of heart, liver, kidney organs
5. Participants in another clinical trial.
Discontinuation criteria
Reasons for discontinuation of treatment may include,
but are not limited to, the following:
1. Participant’s decision to discontinue treatment at any
time for any reason
2. Investigator’s determination to discontinue treatment
for the patient’s safety and best interests at any time
3. Non-compliance of participants with the study pro-
cedure (eg, study visits)
4. Concomitant therapy that could affect the study
results during the trial
5. Detection of protocol violations at any time.
Figure 1 Trial flowchart.
Wang L, et al.BMJ Open 2014;4:e006326. doi:10.1136/bmjopen-2014-006326 3
Open Access
Intervention
Ginger-salt-indirect moxibustion is formulated on the
basis of descriptions in the ancient literature and our
clinical experience. Moxibustion will be manipulated by
certified acupuncturists with at least 20 years’clinical
experience. All treatment details will be standardised
between practitioners by guiding videos and relative
training before the first acupuncture session.
Interventions will be performed in accordance with the
STRICTOM
47
and good clinical practice guidelines
(GCP).
Treatment group A
Participants in treatment group A will receive moxa
cone moxibustion and routine care once a day for
4 weeks. The procedure for each session as it is used in
normal practices is as follows (figure 2). Participants are
asked to lie on a bed in a supine position and remove
clothing to fully expose the navel in a temperature con-
trolled room (25–30°C). A certain amount of salt is put
on the navel to cover Shenque (CV8) acupoint and is
covered by a fresh slice of ginger (30 mm in diameter
and 4–5 mm in thickness). Then a moxa cone ( pure
wormwood fibre in material, 15 mm in diameter and
30 mm in length; Tongrentang Inc, China) is placed on
the fresh ginger slice and lit by the therapist. Once the
moxa cone is burnt out, the therapist removes the whole
moxa cone and replaces it with another one. The tech-
nique requires the participant to experience a sensation
of heat but no painful burning sensation. If participants
feel pain or a burning sensation, the ginger slice with
burning moxa cone will be removed immediately and
reset after several minutes. Each session requires three
units of moxa cone. The therapist is required to observe
the patient carefully and quickly remove the burning ash
to avoid injury. Because this study is designed to evaluate
moxibustion treatment as it is used in normal practice,
the moxibustion group will also receive the usual care
provided to the control group.
Treatment group B
Participants in treatment group B will receive moxa box
moxibustion and routine care once a day for 4 weeks.
The manipulations are generally similar to those in treat-
ment group A. The only difference is that the double-
hole moxa box (13×8×8.5 cm) with two moxa sticks
(pure wormwood fibre, 15 mm in diameter and 70 mm
in length; Tongrentang Inc, China) in the holes will be
placed on the fresh ginger slice (figure 3). The moxa
sticks will be ignited from the bottom. If patients feel
pain, the therapist will remove the lid with the moxa
sticks for several minutes. Each session requires three
units of moxa sticks.
Control group
According to pragmatic design, the control group will
receive routine therapies for stroke recovery. These
include control of blood pressure, inhibition of platelet
aggregation, routine physiotherapy, occupational
therapy, and glucose control treatment. It will be sug-
gested to the participants in this group that they main-
tain their normal lifestyle, including diet, exercise and
workload. Moreover, participants will be encouraged to
inform the researchers of any new treatments performed
after entry into the trial.
Outcome measures
Primary outcome measure
The primary outcome measure will be the increase in
mean volume per void at week 4 from the baseline.
Mean volume per void is one of the main quantitative
indicators recorded in bladder diaries or frequency
volume charts.
17 31 48–50
It is calculated by dividing the
total volume of voluntary urination by the total fre-
quency of voluntary urination, based on 72 h frequency–
volume chart data. The increase in mean volume per
void objectively reflects an improvement in bladder cap-
acity and detrusor stability in the urine filling and
storage period. In a previous study, we observed that
mean volume per void increased in the
ginger-salt-indirect moxibustion group compared to the
control group, the difference being statistically signifi-
cant. Consequently, we selected the increase in mean
volume per void at week 4 from baseline as the primary
outcome. We will also assess the increase in mean
volume per void at week 16 from baseline to evaluate
long term efficacy.
Secondary outcome measures
1. The mean frequency of urination per day, including
voluntary and incontinence urination.
2. Quality of life assessments measured by completion
of the Incontinence Quality of Life Questionnaire
(I-QOL)
51
and the Barthel Index (BI).
52
The average frequency of urination per day is composed
of mean frequency of voluntary and incontinent urin-
ation, which represents the severity of frequent mictur-
ition and UI, respectively. This is strongly linked to the
stability of the bladder and detrusor. Questionnaires for
quality of life assessment will be completed based on the
objective condition and subjective sensation of the
participants.
All outcome measures will be assessed before the base-
line, and at 4 and 16 weeks from the baseline.
Adverse events
Adverse events (AEs) are defined as negative or unin-
tended clinical manifestations following the treatment.
Participants will be instructed to report any abnormal
reactions to the clinical research team at any time. In
addition, study investigators will collect information
about abnormal reactions weekly by visiting the partici-
pants. All details of related and unexpected AEs, such as
time of occurrence, degree of AE, and suspected causes,
will be recorded on Case Report Forms (CRFs). The
common AEs related to moxibustion include allergy,
4Wang L, et al.BMJ Open 2014;4:e006326. doi:10.1136/bmjopen-2014-006326
Open Access
burn and infection.
53
AEs will be classified into five
grades: mild (asymptomatic or mild symptoms; clinical
or diagnostic observations only; intervention not indi-
cated); moderate (minimal, local or non-invasive inter-
vention indicated); severe (severe or medically
significant but not immediately life-threatening; hospital-
isation or prolongation of hospitalisation indicated);
very severe (life-threatening consequences; urgent
intervention indicated); death related to AEs.
Participants with mild and moderate AEs will receive
symptomatic treatment and will be closely followed up
by the research team. Severe AEs will be reported to the
Research Ethics Committee within 48 h. The Research
Ethics Committee will offer medical advice to the
research team and determine whether the patient is eli-
gible for further treatment.
Figure 2 Moxa cone moxibustion.
Figure 3 Moxa box moxibustion.
Wang L, et al.BMJ Open 2014;4:e006326. doi:10.1136/bmjopen-2014-006326 5
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Data management
Before recruitment, the whole research group, including
therapists, data administrators and outcome assessors,
will participate in a training seminar about research con-
tents and data management. Baseline characteristics of
participants will be recorded on CRFs by a research
assistant. Data collection of urination and questionnaires
will be conducted by a researcher who remains blinded
to the group allocation at the baseline, 4 and 16 weeks
from the baseline. Occupational caregivers will be
trained to identify UI and voluntary urination.
Caregivers will collect urine following voluntary urin-
ation and measure it with a pot-shaped urine collector
with scales. They will be trained to record accurate
voiding time, voluntary urinary volume and UI episodes
on a 72 h frequency–volume chart ( figure 4). The
record will be started at 8:00 and last for 72 h. If care-
givers failed to collect urine in time, they will note
voiding time and specific reasons on the chart. The
blinded researcher will complete the urination section
on CRFs according to the 72 h frequency–volume charts
handed in by caregivers.
Two independent researchers blinded to the group
allocation will enter the data on an Excel spreadsheet
after the completion of the CRFs separately. Another
independent researcher will compare the two datasets
for check-up. If different data entry is discovered, data
will be compared with the original CRFs to verify incon-
sistency. All modification will be marked on the CRFs.
Research data will be gathered and saved, abiding by the
Data Protection Act 1998. Paper files will be kept in a
locked filing cabinet. Electronic documents will be
stored in a password protected computer, with access
restricted to the principal investigator. All research docu-
ments will be preserved for at least 5 years after
publication.
Statistical analysis
Data analysis will be performed in a blinded pattern by sta-
tisticians of the Research Center of Clinical Epidemiology
Affiliated to Peking University Third Hospital in China.
Statistical analyses will be conducted on an
intention-to-treat basis using the SPSS statistical package
programme (V.18.0). Missing data will be replaced in
accordance with the principle of the last observation
carried forward. A value of p<0.05 will be considered statis-
tically significant with a two-sided test. Baseline character-
istics including gender, age and previous duration are
described as n (%) for categorical data and mean±SD for
continuous data. To compare the differences among
groups, we will perform analysis of variance for normally
distributed data, the Kruskal-Wallis test for abnormally dis-
tributed data, and the χ
2
test for categorical data.
Comparisons between two groups will be conducted using
the Bonferroni method of post hoc multiple comparisons.
Ethical considerations
This study adheres to the principles of the Declaration
of Helsinki and has been approved by the Research
Ethical Committee of Beijing Hospital of TCM Affiliated
to Capital Medical University (ref: 2013BL-094). We will
conduct the research in the following hospitals: Beijing
TCM Hospital Affiliated to Capital Medical University,
Beijing Huguosi Hospital of TCM and China
Rehabilitation Research Center. Each participant will
sign written informed consents voluntarily.
DISCUSSION
Placebo or sham control is encouraged in clinical trials to
avoid bias.
54
To our knowledge, no consensus has been
established to recommend valid placebo or sham methods
of moxibustion so far. Sham moxibustion is impractical for
blinding purposes because of the common knowledge of
moxibustion among Chinese patients. Owing to the pref-
erence for moxibustion, non-compliance of Chinese
patients will make it difficult to use standard therapies as
control treatment. For pragmatic purposes, we set a usual
care group as a blank control group, rather than a certain
effective therapy or a sham device.
In regard to the evaluation instruments, we selected a
72 h frequency–volume chart to record urination details,
and I-QOL together with BI to assess quality of life. The
frequency–volume chart and bladder diary is highly
recommended in clinical trials by ICS.
1
Frequency–
volume charts record the time and volume of each
voiding, as well as the incontinence episodes. ICS sug-
gested that frequency–volume charts should be recorded
for at least 24 h.
1
A minimum of 72 h was required to
ensure reliability for diary parameters.
48 55–58
Thus, we
will use a 72 h frequency–volume chart to alleviate
burdens for patients and improve compliance.
59 60
As for the assessment of quality of life, I-QOL is strongly
recommended to assess the effect of UI on patient quality
of life.
61
Previous research
51
has affirmed the reliability
and validity of I-QOL as an incontinence-related QOL
instrument in neurogenic UI patients. The items of I-QOL
focus on three dimensions, namely social embarrassment,
avoidance behaviour, and psychosocial impact. BI is added
to evaluate patients’activities of daily living, which is recog-
nised as a valid and reliable outcome measurement for
stroke survivors.
52
Figure 4 72 h frequency–volume chart.
6Wang L, et al.BMJ Open 2014;4:e006326. doi:10.1136/bmjopen-2014-006326
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One limitation of this pilot study is that we will be unable
to prevent therapists and participants from knowing the
group allocation because of the characteristics of moxibus-
tion. To minimise the bias, therapists will receive profes-
sional training and strict quality control. In order to
homogenise the psychological effects, participants are
informed that the effects of the two moxibustion techni-
ques are uncertain. The words ‘placebo’or ‘control’will be
avoided. Similar strategies have been applied in previous
trials.
62 63
Non-compliance of the control group is another
limitation of this pilot trial. It may lead to a high dropout
rate. Participants will be provided with 150 Renminbi
(RMB) as financial compensation to improve compliance.
This study is the major sub-project focusing on stroke
recovery, which is sponsored and funded by the National
Administration of TCM of China. This protocol
describes the first pilot randomised controlled trial
evaluating the feasibility of conducting research to assess
the efficacy and safety of ginger-salt-indirect moxibustion
on UUI after stroke. Results of this preliminary study will
provide essential information for the design of subse-
quent large scale trials. Further trials will focus on the
assessment of urodynamic parameters and evaluation of
efficacy and safety of moxibustion on UUI after stroke.
Acknowledgements We acknowledge State Administration of Traditional
Chinese Medicine of China for agreeing to sponsor this study. The authors
also would like to thank Ines Janowicz for the English language editing, and
the reviewers for their helpful comments on this manuscript.
Contributors LPW and HLL conceived this study and prepared the initial
protocol. LW drafted the manuscript and participated in the design of the
study. GXS, YY, LZ, TZ participated in revising the protocol. LZ plans for the
statistical analysis. LPW and HLL made amendments to the trial protocol. All
authors read and approved the final manuscript.
Funding The trial is sponsored and funded by special project for the national
clinical research bases construction of traditional Chinese medicine belonging
to the State Administration of Traditional Chinese Medicine of the People’s
Republic of China, grant number: JD2X2012152.
Competing interests None.
Patient consent Obtained.
Ethics approval Research ethics approval was attained from the Research
Ethical Committee of Beijing Hospital of Traditional Chinese Medicine
Affiliated to Capital Medical University (ref: 2013BL-094).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The results of this pilot study will be disseminated
via peer reviewed publications and conference presentations. All of the data
are available.
Open Access This is an Open Access article distributed in accordance with
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work non-
commercially, and license their derivative works on different terms, provided
the original work is properly cited and the use is non-commercial. See: http://
creativecommons.org/licenses/by-nc/4.0/
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