Effect Comparison of Electro-acupuncture and Prucalopride for Severe Chronic Constipation: a Randomized Controlled Trial

Study Overview
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Brief Summary
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This trial is primarily aimed to compare the effect and safety of electro-acupuncture and prucalopride for severe chronic constipation: if the short-term effect of electro-acupuncture is no inferior to prucalopride? Besides, the investigators will also mainly confirm the superiority of electro-acupuncture: if the effect of electro-acupuncture can last for 3 6 months? Then, assess the patients' acceptance of electro-acupuncture.

Detailed Description
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Study design: this trial is a multi-central randomized controlled trial which contains 14 centers. Random sequences will be generated by the clinical evaluating center of China Academy of Chinese Medical Sciences. Subjects are patients who have severe chronic constipation. Sample size evaluation: Sample size will be based on the proportion of patients having mean complete spontaneous bowel movements (CSBMs) no less than 3 times per week. The proportion is 31.67% in our phase I clinical trial by using electro-acupuncture, and 30.9% in another trial by using prucalopride.The total sample size is 560. Periods and primary outcome: participants will be assessed at baseline for 2 weeks, treated for 8 weeks, and followed up for 24 weeks. Primary outcome is the proportion of patients having mean CSBMs/week no less than 3 times over the latter 6-week treatment. Quality control: the study is a randomized controlled trial; participants were included strictly; evaluators and statisticians are blinded; quality control officers of 3 different levels will supervise this trial. Data management: this trial will use the Remote Dara Capture (RDC) system for data entering and Data Verification Plan (DVP) for data examining. Statistical analysis: Intention-To-Treat (ITT) analysis will be used in this study. One-sided test (non-inferiority) will be used for testing the primary outcomes; meanwhile, two-sided test will be used for evaluating other outcomes. A P value equal to or less than 0.05 is considered to indicate statistical significance.

Official Title
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Effect Comparison of Electro-acupuncture and Prucalopride for Severe Chronic Constipation: a Multi-center Noninferiority Randomized Controlled Trial

Conditions
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Constipation

Intervention / Treatment
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* Procedure: acupuncture
* Drug: Prucalopride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meeting Rome Ⅲ criteria for diagnosing functional constipation; severe chronic constipation (two or fewer CSBMs per week for more than 3 months）; the weekly mean CSBMs are no more than 2 times during the 2-week baseline aged from 18 to 75 years old no use of drugs for constipation (emergency treatments should be excepted) during at least 2 weeks before enrollment; no acupuncture treatment for constipation in the previous 1 month; never joined any other trial in progress; volunteered to join this research and signed the informed consent Exclusion Criteria: irritable bowel syndrome, organic constipation or secondary constipation caused by endocrine, metabolic, nervous, postoperative diseases, or by drugs; mushy stool or watery stool are showed more than once during baseline when defecating spontaneously without any laxative (Bristol stool type 6 or 7); history of pelvic floor dysfunction; taking medicine in progress which can induce constipation; severe hemorrhoid or anal fissure; constipation with serious cardiovascular, hepatic or renal diseases, cognitive dysfunction, abdominal aortic aneurysm or hepatosplenomegaly, aphasia, mental disorders, or illness which affects the cooperation for examination and treatment; women in gestation or lactation period; blood coagulation disorders or using anticoagulants regularly such as Warfarin and Heparin; cardiac pacemaker carrier.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electro-acupuncture<br>Electro-acupuncture at bilateral ST25, SP14 ,and ST37. Patients will be treated once per day for 30 min, 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. | Procedure: acupuncture<br>* Electro-acupuncture at bilateral ST25, SP14 ,and ST37. Patients will be treated once per day for 30 minutes, 5 times/week for the first 2 weeks and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks.<br>* Other names: eletro-acupuncture;|
| Active Comparator: Prucalopride<br>Prucalopride Succinate taken orally, 2mg/day in the morning before breakfast | Drug: Prucalopride<br>* Prucalopride Succinate will be taken orally at the dose of 2mg/day in the morning before breakfast. Each treatment cycle will be given for continuous 32 weeks.<br>* Other names: serotonin 5-HT(4) receptor agonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Proportion of Participants With ≥3 Mean Weekly CSBMs Over Weeks 3-8 | Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the mean weekly CSBMs of each patient were calculated over weeks 3-8. Second, we got the number of patients with 3 or more mean weekly CSMBs. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: the latter 6 weeks of treatment (weeks 3-8). | over weeks 3-8 (the latter 6-week treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Proportion of Participants With ≥3 Mean Weekly CSBMs Over Weeks 1-2, 11-12, 15-16, 19-20, 31-32. | Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the mean weekly CSBMs of each patient were calculated over weeks 1-2, 11-12, 15-16, 19-20, 31-32. Second, we got the number of patients with 3 or more mean weekly CSMBs. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: weeks 1-2, 11-12, 15-16, 19-20, 31-32. | over weeks 1-2, 11-12, 15-16, 19-20, 31-32. | 
| the Proportion of Participants With ≥1 Increase in Mean Weekly CSBMs From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the increase in mean weekly CSBMs of each patient from baseline were calculated over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. Second, we got the number of patients with ≥1 increase in the mean weekly CSMBs from baseline. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | 
| Mean Weekly CSBMs and Its Change From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. |  | over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | 
| Mean Weekly SBMs and Its Change From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. |  | over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | 
| the Change From Baseline in Mean Score of Stool Consistency for Each SBM Over Weeks 1-2 and 3-8. | The change from baseline in the mean score of stool consistency of each SBM over weeks 1-2 and weeks 3-8. Assessing time: baseline, weeks 1-2 and weeks 3-8. Patients will self-report their stool consistency of each SBM according to the 7-type Bristol Stool Form Scale (scored by 1 to 7 respectively). Type 1: Separate hard lumps, like nuts (hard to pass); Type 2: Sausage-shaped, but lumpy; Type 3: Like a sausage but with cracks on its surface; Type 4: Like a sausage or snake, smooth and soft; Type 5: Soft blobs with clear cut edges (passed easily); Type 6: Fluffy pieces with ragged edges, a mushy stool; Type 7: Watery, no solid pieces. Entirely liquid. Type 3 and 4 were deemed as a normal stool. | over weeks 1-2, 3-8. | 
| the Change From Baseline in Mean Score of Straining for Each SBM Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | The change from baseline in the mean score of straining of each SBM over weeks 1-2, 3-8, 9-12, 9-16, 9-20, 9-32. Assessing time: baseline, weeks 1-2, 3-8, 9-12, 9-16, 9-20, 9-32. Patients will self-report their straining degree of each SBM in the defecation diaries according to the following scale. 0 = not difficult; 1 = a little difficult, need some straining to defecate; 2 = difficult, need straining to defecate; 3 = very difficult, need hard straining to defecate. Higher scores mean a worse outcome. | over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. | 
| Time to the First CSBMs | Abbreviation: CSBMs, complete spontaneous bowel movements. Time to the first CSBMs was counted by days. Rescue medicine or other measurements for constipation is not allowed to be used 48 hours before and after the first treatment for evaluating the time to the first complete spontaneous bowel movement. Participants were assessed after the first treatment until they having their first CSBMs. | from the time of their first treatment to the time they having their first CSBMs | 
| Change From Baseline in Mean Score of Patient Assessment of Constipation Quality of Life | The change from baseline of the score of Patient Assessment of Constipation Quality of Life (PAC-QOL) at week 4 and week 8. PAC-QOL is a self-report questionnaire to evaluate the quality of life in patients with constipation, which was distributed by Mapi Research Trust in France. This questionnaire contains 28 items including 4 basic parts of physical discomfort, worries and concerns, psychosocial discomfort, and satisfaction. We use the Chinese version in our trial. Assessing point: baseline, week 4 and week 8. The score of PAC-QOL ranged from 1 to 5 (1 indicates no discomfort or feeling very satisfied, 5 indicates extreme severity and always appears or feeling very dissatisfied). | week 4 and week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe chronic constipation, randomized controlled, electro-acupuncture, prucalopride