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

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

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.

Study Overview

• Status: Completed
• Conditions: Constipation; Functional Gastrointestinal Disorders
• Intervention / Treatment: Drug: MaZiRenWan (MZRW); Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Hong Kong Baptist University Mr. & Mrs. Chan Hon Yin Chinese Medicine Specialty Clinic and Good Clinical Practice Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MaZiRenWan (MZRW); MZRW granule, 7.5g/sachet	Drug: MaZiRenWan (MZRW); MZRW granule dissolved in 150ml hot water (oral), 7.5g/sachet, twice daily; Other Names: Hemp Seed Pill
Placebo Comparator: Placebo; Placebo granule, 7.5g/sachet	Drug: Placebo; Placebo granule dissolved in 150ml hot water (oral), 7.5g/sachet, twice daily; Other Names: MZRW Placebo

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Hong Kong Baptist University
• Collaborators: Food and Health Bureau, Hong Kong; PuraPharm International (H.K.) Ltd

Publications and helpful links

General Publications

• 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.

Helpful Links

• Abstract

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: August 25, 2008
• First Submitted That Met QC Criteria: August 25, 2008
• First Posted (Estimate): August 26, 2008

Study Record Updates

• Last Update Posted (Estimate): June 24, 2016
• Last Update Submitted That Met QC Criteria: May 23, 2016
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Chinese Herbal Medicine; Traditional Chinese Medicine; Herbal Medicine; Functional Constipation; MaZiRenWan; Hemp Seed Pill
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Gastrointestinal Diseases; Digestive System Diseases; Constipation
• Other Study ID Numbers: PID-002