I) Study period:
14 weeks, including 2 weeks of run-in (wash-out), 6 weeks of treatment, and 6 weeks of
follow-up. 15 visits will be scheduled for each participant, comprising 2 visits during
recruitment and the wash-out period, 12 visits during the treatment period, and 1 visit
at the end of the follow-up period.
II) Coding of data:
The trial uses patient-blind technique, which means needles for acupuncture and sham
acupuncture will be of identical looking and use same package, conduct blinding according
to randomization codes. The study will only be unblinded at final statistical analysis
and in final report. In case of emergency code breaking, before code breaking, the
investigator should well inform the principal investigator of the corresponding
participating site. Investigators who break the codes need to explain the reasons and
document on patients' notes. The following circumstances can be considered for an
emergency breaking, including, but not limited to: (1) When a SAE happens and is
considered to be relevant to experimental medication or placebo; (2) When a serious
complication happens.
III) AE/SAE reporting:
All AEs that not meeting the criteria for SAEs will be captured on the case report form
(CRF). The details include, but not be limited to: (1) date, (2) event description, (3)
time of onset, (4) assessment of severity, (5) relationship to study intervention, and
(6) time of resolution/stabilization of the event. All AEs occurring while on study will
be documented appropriately regardless of relationship. All AEs will be followed to
adequate resolution or stabilization. Any medical condition that is present at the time
that the participant is screened will be considered as baseline and not reported as an
AE. However, if the study participant's condition deteriorates at any time during the
study, it will be recorded as an AE. Changes in the severity of an AE will be documented
to allow an assessment of the duration of the event at each level of severity to be
performed. AEs characterized as intermittent require documentation of onset and duration
of each episode. Regarding SAEs, the study investigator will immediately report to the
principal investigator for any SAE. SAEs will be followed until satisfactory resolution
or until the investigator deems the event to be chronic or the participant is stable.
Other supporting documentation of the event may be requested by the Research Ethics
Committee (REC) and should be provided as soon as possible. All SAE must be evaluated by
the principal investigator and investigators. Once it happened, principal investigator
must submit a SAE report to REC within 24 hours and follow up within 7 days. All AEs and
SAEs will be reported to REC in the annual progress report and in the final study report.
IV) Compliance and dropout:
For maximizing participants' compliances, first, the investigators have a thorough
consent process for all participants by explaining the details of the study schedule,
potential side effects of treatment, the responsibilities the participants needed to take
and together with the support and reassurance during the whole study. Second, the
investigators have a careful scrutiny (2-week run-in period) to exclude ineligible and
low compliance participants before randomization. Third, a special e-mail account and a
direct telephone hotline equipping with this clinical trial are ways for the study team
to actively communicate with participants and reply enquiries. Moreover, extra-visits
will be arranged for participants to see WM doctor or TCM practitioner if participants
develop adverse events before the next scheduled visit. If any patient has thoughts of
withdrawing or dropping out, he/she will try to determine the reason. The investigators
would try to find solution in order to keep the patient in the study.
V) Data collection and management:
Case report forms (CRFs) will be filled in by investigators. Collectable information
includes patient identification and demographic data, clinical history, dietary history,
personal history, family history, substance use, IBS medical history and clinical
examination. Data processing will be conducted in accordance with the following protocol:
Verification of CRFs: Investigators need to verify CRFs before inputting.
Data verification needs to be conducted successively in the following two steps:
Verify the consistency and logicality of data: Review contents of data range
and logicality will be determined by the range of each index and the
interrelation. Corresponding software formula will also be applied to assist
the data input.
Compare database and CRFs by manual testing. Selectively counter check 10% CRFs
with participants' medical notes to check the quality of input and analyze.
Data inspection and closure of database: After verifying the validity of established
database and statistical protocol, principal investigators will lock the data. The
locked data are not allowed to change. Confirmed problems found after locking will
be handled in the process of statistical analysis. All mistakes and modification
should be recorded and kept properly.
Investigators should keep all trial materials, including acknowledgement of all
participants, original informed consent forms with participant's signature, all CRFs and
detailed record of medications distribution, which should be provided to ethics committee
and drug supervision and administration department for reviewing. All files will be
maintained in storage for a period of 7 years after the completion of the clinical trial.
Data access during study will be restricted except investigators, ethics committee, and
government authority. After the study, all the data will be deidentified and available
for sharing upon reasonable request.
VI) Sample size calculation:
The study is the first sham-controlled acupuncture trial that uses the Food and Drug
Administration (FDA) recommended end point for IBS-C. The sample size was determined
based on the study's purpose, statistical precision, feasibility, and reported
improvements in clinical symptoms (abdominal pain, bloating, feeling of incomplete
defecation, stool frequency, stool shape) from previous acupuncture studies on IBS-C
patients. With an alpha of 0.05, a power of 0.8, a 20% dropout rate, and the potential
for missing data, a total sample size of 60 patients (30 in experimental arm and 30 in
control arm) is required.
VII) Statistical analysis:
All efficacy and safety analyses will be conducted based on intention-to-treat (ITT)
principle. Missing values will be imputed by the last-observation-carried-forward method.
The statistical analysis will be performed using the Stata software. The statistical
significance will be defined as two-sided P-value of <0.05. Baseline characteristics will
be reported as mean (SD). Baseline differences between the groups will be evaluated with
the application of Student's t-test for normally distributed continuous variables and
non-parametric Mann-Whitney U test for non-normally distributed variables. For
categorical variables, chi-squared test or Fisher's exact test will be applied.
Comparisons between groups will be conducted by using unpaired t-test for normally
distributed data and Mann-Whitney test for non-normally distributed data. Within group
differences will be evaluated with paired t-test for normally distributed data and
Wilcoxon signed-rank test for non-normally distributed data.