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

This study has been completed.
Sponsor:
Collaborators:
Food and Health Bureau, Hong Kong
PuraPharm International (H.K.) Ltd
Information provided by (Responsible Party):
ZhaoXiang Bian, Hong Kong Baptist University
ClinicalTrials.gov Identifier:
NCT00741936
First received: August 25, 2008
Last updated: November 14, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Functional Gastrointestinal Disorders
Constipation
Drug: MaZiRenWan (MZRW)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Chinese Herbal Medicine for Functional Constipation: A Randomized, Double-blind, Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by Hong Kong Baptist University:

Primary Outcome Measures:
  • Responder of Complete Spontaneous Bowel Movement (CSBM) [ Time Frame: End of treatment (wk10) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Responder of Complete Spontaneous Bowel Movement (CSBM) [ Time Frame: End of follow up (wk18) ] [ Designated as safety issue: No ]

    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.


  • Bowel Movement [ Time Frame: Baseline(Wk1&2), Within treatment(Wk3-10) & Within follow-up(Wk11-18) ] [ Designated as safety issue: No ]
  • Complete Spontaneous Bowel Movement (CSBM) [ Time Frame: Baseline(Wk1&2), Within treatment(Wk3-10), Within follow-up(Wk11-18) ] [ Designated as safety issue: No ]
  • Changes on Individual Symptom Scores [ Time Frame: Baseline(Wk2), Within treatment(Wk6), End of treatment(Wk10) & End of follow-up(Wk18) ] [ Designated as safety issue: No ]
    It was a 7-point ordinal scale from 0=not at all to 6=very severe.

  • Global Symptoms Improvement [ Time Frame: Wk 6, 10 & wk 18 ] [ Designated as safety issue: No ]
    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.

  • Success of Blinding [ Time Frame: End of follow-up (Wk18) ] [ Designated as safety issue: No ]
    The success of blinding was evaluated for both investigator and patients as to whether MZRW or placebo had been taken.

  • Blood Urea Level [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  • Blood Creatinine Level [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  • Serum Glutamic Pyruvic Transaminase(SGPT) Level [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  • Serum Glutamic Oxaloacetic Transaminase (SGOT) [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]

Enrollment: 120
Study Start Date: July 2008
Study Completion Date: December 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741936

Locations
China
Hong Kong Baptist University Mr. & Mrs. Chan Hon Yin Chinese Medicine Specialty Clinic and Good Clinical Practice Centre
Hong Kong, China
Sponsors and Collaborators
Hong Kong Baptist University
Food and Health Bureau, Hong Kong
PuraPharm International (H.K.) Ltd
Investigators
Principal Investigator: Zhao-xiang Bian, PhD Hong Kong Baptist University
  More Information

Additional Information:
Publications:
Responsible Party: ZhaoXiang Bian, Professor, Director of Clinical Division, Hong Kong Baptist University
ClinicalTrials.gov Identifier: NCT00741936     History of Changes
Other Study ID Numbers: PID-002
Study First Received: August 25, 2008
Results First Received: August 2, 2011
Last Updated: November 14, 2011
Health Authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee

Keywords provided by Hong Kong Baptist University:
Functional Constipation
Chinese Herbal Medicine
MaZiRenWan
Hemp Seed Pill
Traditional Chinese Medicine
Herbal Medicine

Additional relevant MeSH terms:
Constipation
Digestive System Diseases
Gastrointestinal Diseases
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on September 30, 2014