Electro-acupuncture for Irritable Bowel Syndrome With Constipation

Irritable Bowel Syndrome With Constipation Clinical Trial

Official title:

Electro-acupuncture for Irritable Bowel Syndrome With Constipation: a Pilot, Randomized, Double-blinded, Sham-controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06219707
• Other study ID #: IRB-2023-451
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: December 1, 2025

Study information

• Verified date: January 2024
• Source: Nanyang Technological University
• Contact: Linda LD Zhong, MD., PhD
• Phone: (+65) 67911744
• Email: linda.zhong[@]ntu.edu.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the clinical trial is to evaluate the efficacy and safety of electro-acupuncture for irritable bowel syndrome with constipation (IBS-C) patients. 60 IBS-C patients will be randomized and allocated to either the electro-acupuncture arm or the sham acupuncture arm.

Description:

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, we 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, we 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. We 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:

1. Verification of CRFs: Investigators need to verify CRFs before inputting.

2. Data verification needs to be conducted successively in the following two steps:

1. 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.

2. Compare database and CRFs by manual testing. Selectively counter check 10% CRFs with participants' medical notes to check the quality of input and analyze.

3. 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:

Different from published studies on IBS-C patients, our study uses sham acupuncture as the control group. Based on the reported clinical symptoms (abdominal pain, bloating, feeling of incomplete defecation, stool frequency, stool shape) scores improvements, we expect a mean difference of 2.56 between groups. With alpha of 0.05, power of 0.8, 20% dropout rate, and possible missing data, a total sample size of 60 patients (30 in experimental arm and 30 in control arm) will be 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Fulfilment of the Rome IV criteria for IBS-C [4];

2. Age of 21 to 65 years (inclusive);

3. IBS Symptom Severity Scale (IBS-SSS) > 75 points (a range of 0-500 points of VAS on five questions) at baseline and during the 2-week run-in period;

4. Written informed consent.

Exclusion Criteria:

1. Pregnancy or breast-feeding;

2. Medical history of inflammatory bowel diseases, carbohydrate malabsorption, hormonal disorder, known allergies to food additives, and/or any other serious diseases;

3. Unstable medical conditions;

4. Diagnosed with primary severe mental illness;

5. Patients who have received acupuncture treatment in last three months, or took concomitant medication with affect gastrointestinal motility or visceral sensation, such as antidiarrheal agent, antidepressant, narcotic analgesic, and anticholinergic;

6. Alcoholism or drug abuse in past 1 year;

7. Having needle phobia.

Related Conditions & MeSH terms

• Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Constipation
• Syndrome

Intervention

Device:
• Acupuncture needles
The acupuncture needles and related equipment will have already received approval for routine Traditional Chinese Medicine (TCM) clinical practice in Singapore.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Nanyang Technological University	National University of Singapore

References & Publications (4)

Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008 May 29;358(22):2344-54. doi: 10.1056/NEJMoa0800670. — View Citation

Han JS. Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci. 2003 Jan;26(1):17-22. doi: 10.1016/s0166-2236(02)00006-1. No abstract available. — View Citation

Liu Z, Yan S, Wu J, He L, Li N, Dong G, Fang J, Fu W, Fu L, Sun J, Wang L, Wang S, Yang J, Zhang H, Zhang J, Zhao J, Zhou W, Zhou Z, Ai Y, Zhou K, Liu J, Xu H, Cai Y, Liu B. Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial. Ann Intern Med. 2016 Dec 6;165(11):761-769. doi: 10.7326/M15-3118. Epub 2016 Sep 13. — View Citation

Schmulson MJ, Drossman DA. What Is New in Rome IV. J Neurogastroenterol Motil. 2017 Apr 30;23(2):151-163. doi: 10.5056/jnm16214. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Responders have on average, 3 or more spontaneous, complete bowel movements per week [3]	Responders have on average, 3 or more spontaneous, complete bowel movements per week during the 12 weeks of the trial	Baseline (week 2), after treatment period (week 8), end of follow-up (week 14)
Secondary	Proportion of patients with an average increase of 1 or more spontaneous, complete bowel movements per week	Proportion of patients with an average increase of 1 or more spontaneous, complete bowel movements per week as compared with the baseline number.	Baseline, week 8, week 14
Secondary	Average number of spontaneous, complete bowel movements per week	Average number of spontaneous, complete bowel movements per week as compared with the baseline number.	Baseline, week 8, week 14
Secondary	Percentage of bowel movements with normal consistency	Percentage of bowel movements with normal consistency as compared with the baseline number.	Baseline, week 8, week 14
Secondary	Percentage of bowel movements with severe or very severe straining during defecation	Percentage of bowel movements with severe or very severe straining during defecation as compared with the baseline number.	Baseline, week 8, week 14
Secondary	Median time to the first spontaneous, complete bowel movement after electro-acupuncture	Median time to the first spontaneous, complete bowel movement after intake of the first session of electro-acupuncture.	From first session of electro-acupuncture up to the end of follow-up, approximately 12 weeks
Secondary	Average number of bisacodyl tablets or enemas used per week	Average number of bisacodyl tablets or enemas used per week as compared with the baseline number.	Baseline, week 8, week 14
Secondary	Global assessment of efficacy of treatment with Likert scale	Global assessment of efficacy of treatment with Likert scale at weeks 2, 5, 8, and 14	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the IBS-C symtoms using IBS Symptom Severity Scale (IBS-SSS)	IBS-SSS is a questionnaire used to assess the severity of symptoms in individuals with Irritable Bowel Syndrome (IBS). It typically includes questions related to abdominal pain, bloating, stool consistency, and the impact of IBS symptoms on daily life. Higher scores on this scale indicate more severe symptoms.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the IBS-C symtoms using IBS Quality of Life (IBS-QOL)	IBS-QOL is a measure designed to assess the impact of IBS on a person's quality of life. It includes questions related to how IBS symptoms affect various aspects of daily functioning, such as physical health, emotional well-being, and social activities. Lower scores on this scale indicate a lower quality of life due to IBS.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the IBS-C symtoms using Patient Assessment of Constipation Symptoms (PAC-SYM)	PAC-SYM is a questionnaire used to evaluate the severity and frequency of constipation-related symptoms in patients. It typically covers symptoms like abdominal discomfort, straining during bowel movements, and incomplete evacuation. Higher scores suggest more severe constipation symptoms.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the IBS-C symtoms using Constipation Quality of Life (PAC-QOL)	PAC-QOL is a measure that assesses the impact of constipation on a person's quality of life. It includes questions about how constipation symptoms affect daily activities, emotional well-being, and overall satisfaction with life. Lower scores indicate a poorer quality of life related to constipation.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the IBS-C symtoms using Patient Health Questionnaire-15 (PHQ-15)	PHQ-15 is a self-report questionnaire that assesses somatic symptom severity in individuals. It includes questions related to various physical symptoms, such as headaches, back pain, and stomach discomfort. It is often used as a screening tool to assess somatic symptom burden, and higher scores indicate a greater presence of somatic symptoms.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using Hamilton Depression Scale (HAMD)	HAMD is a clinician-administered questionnaire used to assess the severity of depressive symptoms in individuals with depression. It includes items related to mood, feelings of guilt, sleep disturbances, and physical symptoms. Higher scores indicate more severe depression.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using Self-rating Depression Scale (SDS)	SDS is a self-report questionnaire designed to assess the presence and severity of depressive symptoms from the perspective of the individual. It includes questions about mood, feelings of sadness, and physical symptoms associated with depression. Higher scores suggest greater self-reported depression.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using Patient Health Questionnaire (PHQ-9)	PHQ-9 is a widely used self-report tool for assessing depression. It consists of nine questions that correspond to the criteria for major depressive disorder. Individuals rate the frequency of their symptoms over the past two weeks. Higher scores indicate more severe depression.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using General Anxiety Disorder (GAD-7)	GAD-7 is a self-report questionnaire used to assess the presence and severity of generalized anxiety disorder symptoms. It includes questions related to excessive worry, restlessness, and physical symptoms associated with anxiety. Higher scores indicate greater anxiety.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using Hospital Anxiety and Depression Scale (HADS)	HADS is a self-report questionnaire that assesses both anxiety and depression symptoms in individuals, often used in healthcare settings. It includes items related to mood, anxiety, and physical symptoms. It provides separate scores for anxiety and depression.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using Visceral Sensitivity Index (VSI)	VSI is a self-report questionnaire used to assess the degree of visceral hypersensitivity in individuals with conditions like irritable bowel syndrome. It includes questions about gastrointestinal symptoms and discomfort, helping to measure sensitivity to visceral sensations.	Baseline, week 5, week 8, week 14
Secondary	Change from baseline in the psychological conditions using Perceived Stress Scale (PSS)	PSS is a self-report questionnaire that measures an individual's perception of stress in their life. It includes questions about how often one perceives situations as stressful and their ability to cope with stress. Higher scores indicate greater perceived stress.	Baseline, week 5, week 8, week 14