A Double-blinded,Double-dummy Clinical Trial of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy and safety of a Chinese herbal proprietary medicine, MaZiRenWan (MZRW), by comparing with stimulant laxative western medicine (WM), senna, and placebo for patients with functional constipation (FC) in excessive TCM syndrome.

Detailed Description
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Functional constipation (FC) is a common clinical complaint. Despite the effectiveness of MaZiRenWan (MZRW) for alleviating FC symptoms has been proofed in the previous study.Given the results of the dose determination study and placebo-controlled study of MZRW, we hypothesize that MZRW is more useful than senna (senokot), a commonly used WM drug for constipation, for FC patients in excessive TCM syndrome.This is a prospective, double-blind, double dummy, randomized, controlled trial. After a 2-week run-in, eligible FC patients (Rome III) in excessive TCM syndrome will randomly be assigned to CHM arm (MZRW and WM placebo), WM arm (senna and CHM placebo) or placebo arm (CHM placebo and WM placebo). Patients will undergo an 8-week treatment and an 8-week follow-up.

Official Title
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Chinese Herbal Medicine (MaZhiRenWan) for Functional Constipation: a Prospective, Double-blinded, Double-dummy, Randomized Controlled Study

Conditions
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Functional Constipation, Gastrointestinal Disorders

Intervention / Treatment
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* Drug: MZRW
* Drug: Senna
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: either gender aged 18 to 65 years have FC diagnosed as Rome III criterial have diagnosis of Excessive Constipation according to the TCM theory complete spontaneous bowel movement (CSBM) ≦2times/w severity of constipation≧3pts (7 pts scale from 0 to 6pts) and the overall scoring of constipation-related symptoms≧6pts (6items in 7pts scale) for self symptom assessment in the run-in period normal colonic evaluation (colonoscopy or barium enema) within 12 months normal liver and renal function in blood test within 3 months Exclusion Criteria: drug-induced constipation secondary causes of constipation (i.e. medical history of diabetes mellitus and thyroid disease) abdominal surgery (i.e. Caesarean operation) severe diseases (i.e. cancer and acute present asthma) allergy to CHM (i.e. G6PD deficiency), senna and tartrazine pregnancy or breast-feeding psychiatric or addictive disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MZRW<br>MZRW is composed of Fructus Cannabis (HuoMaRen), Radix et Rhizoma Rhei (DaHuang), Radix Paeoniae Alba (BaiShao), Semen Armeniacae Amarum (KuXingRen), Fructus Aurantii Immaturus (ZhiShi) and Cortex Magnoliae Officinalis (HouPo). | Drug: MZRW<br>* Patients are instructed to dissolve a sachet of granules (7.5g) in 150ml of hot water; they take this solution orally twice daily for 8 weeks.<br>* Other names: Hemp Seed Pill;Drug: placebo<br>* The placebo MZRW is made from dextrin (76.03%), tea essence (23.61%), gardenin (0.02%) and caramel (0.34%) to achieve color, smell, taste and texture comparable to MZRW granules.The placebo Senna is made of starch and colour to achieve comparable appearance to Senokot.<br>|
| Active Comparator: Senna<br>Senna is a stimulant laxative which facilitates the passage of stools by altering intestinal electrolyte transport and increasing intestinal motor activity. | Drug: Senna<br>* Patients are instructed to take 2 tablets at the bedtime for 8 weeks.<br>* Other names: Senokot;Drug: placebo<br>* The placebo MZRW is made from dextrin (76.03%), tea essence (23.61%), gardenin (0.02%) and caramel (0.34%) to achieve color, smell, taste and texture comparable to MZRW granules.The placebo Senna is made of starch and colour to achieve comparable appearance to Senokot.<br>|
| Placebo Comparator: Placebo<br>Placebo MZRW and Placebo Senna | Drug: placebo<br>* The placebo MZRW is made from dextrin (76.03%), tea essence (23.61%), gardenin (0.02%) and caramel (0.34%) to achieve color, smell, taste and texture comparable to MZRW granules.The placebo Senna is made of starch and colour to achieve comparable appearance to Senokot.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the responder rate for CSBM during the treatment period | a clinically meaningful endpoint by combining an objective measure (number of bowel movement) with a subjective measure (feelings of patients as to completeness of defecation,Patients with a mean increase of ≧1 complete spontaneous bowel movement(CSBM)/wk compared with the baseline(wk1-2) will be defined as responders | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the responder rate for CSBM during the follow-up period | Participants with a mean increase of complete spontaneous bowel movement (CSBM)>=1 movement per week compared with the last 14 days of the run-in period were defined as responders | 8 weeks | 
| Individual assessment of constipation and related symptoms | severity of constipation, sensation of straining, incomplete evacuation, bloating, abdominal pain / cramping, nausea, and passing of gas) was recorded using a 7-point ordinal scale (0 = not at all and 6 = very severe | 18 weeks | 
| the changes of colonic transit time | It is estimated by using a commercially available radio-opaque Sitzmarks capsule (Konsyl Pharmaceuticals, US). Each gelatine capsule contained 24 barium sulphate embedded polyvinyl chloride markers measuring 1mmx4.5mm. Plain radiographs of the abdomen will be obtained after the swallow of capsule for five days (120 hours) before and after 8 weeks treatment period. | 18 weeks | 
| Global symptom assessment | Participants were asked to rate their impression of change in constipation by comparing with their baseline (Wk2) at the visits during the treatment (Wk6), end of treatment (Wk10) and end of follow-up (Wk18) with scores from 0 to 6 represented markedly worse or better respectively. The response categories were collapsed to simply improved for score 4 to 6, same for score 3 or worse for score 0 to 2. | 18 weeks | 
| Success of blinding | the success of blinding is evaluated for both investigator and patients as to whether CHM, WM or placebo had been taken | 18 weeks | 
| safety profiles | Assessed by determining the important adverse events reported in the participants ' diaries, follow-up interviews,and clinical laboratory evaluationse.g., liver and renal function. | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized controlled trial, Drugs,Chinese Herbal, Constipation/drug therapy