Clinical trial NCT00741936: An Effectiveness and Safety Study of Chinese Herbal Medicine for Functional Constipation
Official title: Chinese Herbal Medicine for Functional Constipation: A Randomized, Double-blind, Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Functional Gastrointestinal Disorders
Constipation
Keywords: Functional Constipation
Chinese Herbal Medicine
MaZiRenWan
Hemp Seed Pill
Traditional Chinese Medicine
Herbal Medicine
Lead sponsor: Hong Kong Baptist University
Sponsor class: OTHER
Collaborators: name: Food and Health Bureau, Hong Kong
name: Purapharm International (Hk) Ltd.
First posted: 2008-08-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Responder of Complete Spontaneous Bowel Movement (CSBM)
timeFrame: End of treatment (wk10)
Secondary outcomes:
measure: Responder of Complete Spontaneous Bowel Movement (CSBM)
timeFrame: End of follow up (wk18)
measure: Bowel Movement
timeFrame: Baseline(Wk1&2), Within treatment(Wk3-10) & Within follow-up(Wk11-18)
measure: Complete Spontaneous Bowel Movement (CSBM)
timeFrame: Baseline(Wk1&2), Within treatment(Wk3-10), Within follow-up(Wk11-18)
measure: Changes on Individual Symptom Scores
timeFrame: Baseline(Wk2), Within treatment(Wk6), End of treatment(Wk10) & End of follow-up(Wk18)
measure: Global Symptoms Improvement
timeFrame: Wk 6, 10 & wk 18
measure: Success of Blinding
timeFrame: End of follow-up (Wk18)
measure: Blood Urea Level
timeFrame: Pre-treatment (Wk2) & Post-treatment (Wk10)
measure: Blood Creatinine Level
timeFrame: Pre-treatment (Wk2) & Post-treatment (Wk10)
measure: Serum Glutamic Pyruvic Transaminase(SGPT) Level
timeFrame: Pre-treatment (Wk2) & Post-treatment (Wk10)
measure: Serum Glutamic Oxaloacetic Transaminase (SGOT)
timeFrame: Pre-treatment (Wk2) & Post-treatment (Wk10)
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Hong Kong Baptist University Mr. & Mrs. Chan Hon Yin Chinese Medicine Specialty Clinic and Good Clinical Practice Centre
Study officials:
affiliation: Hong Kong Baptist University
name: Zhao-xiang Bian, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cheng CW, Bian ZX, Zhu LX, Wu JC, Sung JJ. Efficacy of a Chinese herbal proprietary medicine (Hemp Seed Pill) for functional constipation. Am J Gastroenterol. 2011 Jan;106(1):120-9. doi: 10.1038/ajg.2010.305. Epub 2010 Nov 2.