An Effectiveness and Safety Study of Chinese Herbal Medicine for Functional Constipation

Study Overview
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Brief Summary
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Functional constipation (FC) is a common complaint in clinical practice, but treatment for this condition in conventional medicine is suboptimal. Complementary and alternative medicines, especially Chinese herbal medicine (CHM) are used frequently by patients, however, there is little research evidence about these commonly used CHM. The purpose of the study is evaluate the efficacy and safety of an ancient CHM formula, MaZiRenWan (MZRW), by comparing with placebo.

Detailed Description
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Constipation is a common gastrointestinal complaint in clinical practice, which affects in estimated 12%-19% of American, 14% of Asian, and up to 27% of the population depending on demographic factor, sampling, and definition. With the unsatisfactory response to current symptomatic treatments, many patients seek help from traditional Chinese medicine (TCM), mostly by taking Chinese herbal medicine (CHM). According to the TCM theory, constipation can be broadly divided into two types, excessive and deficient, based on the underlying aetiology. The former is characterized by the presence of Heat or pathological accumulation of Qi. Heat causes constipation by drying the Intestines and the stool. Patients present with hard, dry, pellet like stool, red complexion, dry mouth or halitosis, red tongue with a dry yellow coat, and slippery and rapid pulse. Qi stagnation causes constipation by disrupting the normal movement and descent of Stomach and Intestinal Qi. Patients present difficulty in passing stools, feelings of incomplete evacuation, abdominal distension or pain, frequent belching and flatulence, tongue with thin coat and wiry pulse. The latter, deficient constipation, is delineated as the dryness from insufficient fluid lubrication in the form of blood or lack of propulsion power from the deficiency of Qi or Yang. Besides, the treatment approaches vary from syndrome to syndrome. The formula of MaZiRenWan (MZRW) composed of six Chinese herbs is firstly recorded in a TCM classic, Discussion of Cold-induced Disorders (Shang Han Lun), and it has been commonly used for constipation in excessive pattern throughout Asia since the Han Dynasty (A.D. 200). By combining the actions of these herbs, MZRW can moisten the Intestines, drain heat, promote the movement of Qi and unblock the bowel. Although previous studies show that MZRW has purgative and laxative effects and may be useful for functional constipation (FC), there are significant methodological weaknesses. Furthermore, the dose of CHM intervention being investigated from the first randomized controlled trial (RCT) published in 1983 is always based on the practitioner's experience, TCM literatures, or experts' comments, but not the results from stringent clinical trials, such as dose determination study. Therefore, the evidence produced will be attenuated or even misleading if improper dose is taken. In the present study, the efficacy and safety of MZRW in optimal dosage were justified by comparing with placebo under strict clinical trial design.

Official Title
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Chinese Herbal Medicine for Functional Constipation: A Randomized, Double-blind, Placebo Controlled Trial

Conditions
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Functional Gastrointestinal Disorders, Constipation

Intervention / Treatment
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* Drug: MaZiRenWan (MZRW)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet of Rome III diagnostic criteria of functional constipation Meet the diagnosis of Excessive Constipation according to the TCM theory Age of 18 to 65 years (inclusive) Complete spontaneous bowel movement (CSBM)≦2times/wk Severity of constipation≧4pts (7 pts scale from 0 to 6pts) and the overall scoring of constipation-related symptoms≧8pts (6items in 7pts scale) for self symptom assessment in the run-in period Normal colonic evaluation (colonoscopy or barium enema) within 5 years 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 disease (i.e. cancer and acute present asthma) Allergy to CHM (i.e. G6PD deficiency) 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: MaZiRenWan (MZRW)<br>MZRW granule, 7.5g/sachet | Drug: MaZiRenWan (MZRW)<br>* MZRW granule dissolved in 150ml hot water (oral), 7.5g/sachet, twice daily<br>* Other names: Hemp Seed Pill;|
| Placebo Comparator: Placebo<br>Placebo granule, 7.5g/sachet | Drug: Placebo<br>* Placebo granule dissolved in 150ml hot water (oral), 7.5g/sachet, twice daily<br>* Other names: MZRW Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder of Complete Spontaneous Bowel Movement (CSBM) | Patients with a mean increase of ≧1 complete spontaneous bowel movement(CSBM)/wk compared with the baseline(wk1-2) will be defined as responders. CSBM referred to the feeling that defecation led to complete passage of stool rather than partial or incomplete evacuation without the use of any laxative or enema within 24 hours. | End of treatment (wk10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder of Complete Spontaneous Bowel Movement (CSBM) | 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. CSBM referred to the feeling that defecation led to complete passage of stool rather than partial or incomplete evacuation without the use of any laxative or enema within 24 hours. | End of follow up (wk18) | 
| Bowel Movement |  | Baseline(Wk1&2), Within treatment(Wk3-10) & Within follow-up(Wk11-18) | 
| Complete Spontaneous Bowel Movement (CSBM) |  | Baseline(Wk1&2), Within treatment(Wk3-10), Within follow-up(Wk11-18) | 
| Changes on Individual Symptom Scores | It was a 7-point ordinal scale from 0=not at all to 6=very severe. | Baseline(Wk2), Within treatment(Wk6), End of treatment(Wk10) & End of follow-up(Wk18) | 
| Global Symptoms Improvement | 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. | Wk 6, 10 & wk 18 | 
| Success of Blinding | The success of blinding was evaluated for both investigator and patients as to whether MZRW or placebo had been taken. | End of follow-up (Wk18) | 
| Blood Urea Level |  | Pre-treatment (Wk2) & Post-treatment (Wk10) | 
| Blood Creatinine Level |  | Pre-treatment (Wk2) & Post-treatment (Wk10) | 
| Serum Glutamic Pyruvic Transaminase(SGPT) Level |  | Pre-treatment (Wk2) & Post-treatment (Wk10) | 
| Serum Glutamic Oxaloacetic Transaminase (SGOT) |  | Pre-treatment (Wk2) & Post-treatment (Wk10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional Constipation, Chinese Herbal Medicine, MaZiRenWan, Hemp Seed Pill, Traditional Chinese Medicine, Herbal Medicine