A Dose Determination Study of Chinese Herbal Medicine for Functional Constipation

A Randomized Controlled Trial of Chinese Herbal Medicine in Three-dose Regimen for the Treatment of Functional Constipation

Functional constipation (FC) is common with 14.3% estimated prevalence in Hong Kong, but treatment for this condition in conventional medicine is suboptimal. Complementary and alternative medicines, especially Chinese herbal medicine (CHM) are used frequently by patients with FC, but there is little research evidence about these commonly used CHM. The purpose of the study is evaluate the efficacy and safety of CHM, as well as determining the optimal dosage.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: MaZiRenWan (MZRW) Low dose; Drug: MaZiRenWan (MZRW) Median dose; Drug: MaZiRenWan (MZRW) High dose

Detailed Description

Functional constipation (FC) is a common complaint in clinical practice, with the estimated prevalence 14.3% in Hong Kong, as nearly affecting 1 million Hong Kong People in different extent. It is comparable with western population, which is 15% in North America. By the definition of Rome II criteria, FC comprises a group of functional disorders, which presents as persistent difficult, infrequent or seemingly incomplete defecation.

Constipation is often perceived to be benign, easily treated condition with short-term treatment being relatively straightforward. However, the fact is the management of FC is perplexed as some subjects complain of constipation more than decade. Moreover, chronic constipation can develop into more serious bowel complaints, such as faecal impaction, incontinence and bowel perforations. There is also accumulating evidence shown that constipated subjects have significantly higher anxiety and depression scores and lower quality of life. Therefore, the demand of effective agents to normalize bowel function is extremely large.

Conventional treatment for constipation mainly relies on dietary fibre and laxatives. Although there is no credible evidence that any serious problem is associated with their prolonged use, the treatment of it has been suboptimal. First, a recent systematic review pointed out that there were paucity of trials for many commonly used agents, therefore, their use might not be well validated. Second, many patients with severe constipation do not respond adequately or lose of effectiveness after a short period of time. Third, many patients who intake dietary fibre complain of flatulence, distension, bloating and poor taste. As a result, the compliance is low as about 50%. Fourth, the use of osmotic laxatives, such as polyethylene glycol, become increasingly popular due to fewer side effects and better taste, however, the prices are much more expensive than other medications. Many constipation sufferers seek help from alternative medicine, especially from Chinese herbal medicine. For example, according to a telephone survey in Hong Kong, more than 85% of constipated subjects seek for coping strategies, such as asking for medical consultations, taking prescribed medicine and seeking for alternative therapy, involving Chinese medicine.

Traditional Chinese medicine (TCM) is particularly attractive as their effectiveness in treating functional disorders and retaining balance of body functions. The CHM used in study is derived from classic text of Chinese medicine (Shang Han Lun, Discussion of Cold-induced Disorders), which can "moisten the intestines, drain heat, promote the movement of qi and unblock the bowel".

It is well known that randomized controlled trial (RCT) is the gold standard to test the efficacy of intervention, thus in this project, we attempt to follow the basic requirements of RCT to testify the efficacy and safety of CHM on FC, as well as to determine the optimal dosage. We believe such study will benefit the advancement of CHM, or even as the foundation of research study in future.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Hong Kong Baptist University Chinese Medicine Clinic

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:

• Clinical diagnosis of functional constipation with Rome II criteria
• General stool type belongs to Type 1 to 4 according to Bristol Stool Form Scale
• Complete spontaneous bowel movement≦2 movements per week

Exclusion Criteria:

• Anti-diarrhoeal therapy
• Drug-induced constipation
• Medical history of important bowel pathology, such as inflammatory bowel disease, congenital or acquired megacolon / megarectum
• Medical history of previous abdominal surgery
• Taking chronic medications that contain any kind of herbs, mineral, or specific vitamin supplements
• Medical history of carbohydrate malabsorption, hormonal disorder, cancer, diabetes mellitus, hypothyroidism, asthma, renal impairment and/or any other serious diseases
• History of laxative abuse
• History of allergy to Chinese herbal medicine
• Psychiatric or addictive disorders
• Pregnancy or breast-feeding
• Any other serious diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MaZiRenWan (MZRW) Low dose; MaZiRenWan (MZRW) Low dose 2.5g sachet by mouth, twice daily for 8 weeks	Drug: MaZiRenWan (MZRW) Low dose; Dissolved MaZiRenWan (MZRW) granule (2.5g/sachet) in 150 ml hot water, take orally twice daily for 8 weeks; Other Names: Hemp Seed Pill
EXPERIMENTAL: MaZiRenWan (MZRW) Median dose; MaZiRenWan (MZRW) Median dose 5.0g sachet by mouth, twice daily for 8 weeks	Drug: MaZiRenWan (MZRW) Median dose; Dissolved MaZiRenWan (MZRW) granule (5.0g/sachet) in 150 ml hot water, take orally twice daily for 8 weeks; Other Names: Hemp Seed Pill
EXPERIMENTAL: MaZiRenWan (MZRW) High dose; MaZiRenWan (MZRW) High dose 7.5g sachet by mouth, twice daily for 8 weeks	Drug: MaZiRenWan (MZRW) High dose; Dissolved MaZiRenWan (MZRW) granule (7.5g/sachet) in 150 ml hot water, take orally twice daily for 8 weeks; Other Names: Hemp Seed Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder for Complete Spontaneous Bowel Movement (CSBM)	Participants with a mean increase of 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.	Week3-10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder for Complete Spontaneous Bowel Movement (CSBM)	Participants with a mean increase of 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.	Week11-18
Bowel Movement		Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18)
Complete Spontaneous Bowel Movement (CSBM)	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.	Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18)
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.	Week6, 10 & 18
Severity of Constipation	It was a 7-point ordinal scale from 0=not at all to 6=very severe.	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
Sensation of Straining	It was a 7-point ordinal scale from 0=not at all to 6=very severe.	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
Incomplete of Evacuation	It was a 7-point ordinal scale from 0=not at all to 6=very severe.	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
Sensation of Bloating	It was a 7-point ordinal scale from 0=not at all to 6=very severe.	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
Sensation of Abdominal Pain/Cramping	It was a 7-point ordinal scale from 0=not at all to 6=very severe.	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
Passing of Gas	It was a 7-point ordinal scale from 0=not at all to 6=very severe.	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
Adverse Effects (e.g. Renal and Liver Function Tests)		pre-treatment & post-treatment
Blood Urea Level		Pre-treatment(Week2) & Post-treatment(Week10)
Blood Creatinine Level		Pre-treatment(Week2) & Post-treatment(Week10)
Serum Glutamic Pyruvic Transaminase(SGPT) Level		Pre-treatment(Week2) & Post-treatment(Week10)
Serum Glutamic Oxaloacetic Transaminase(SGOT) Level		Pre-treatment(Week2) & Post-treatment(Week10)

Collaborators and Investigators

• Sponsor: Hong Kong Baptist University
• Investigators: Principal Investigator: ZhaoXiang Bian, PhD, Hong Kong Baptist University

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: October 1, 2006
• Primary Completion (ACTUAL): August 1, 2007
• Study Completion (ACTUAL): October 1, 2007

Study Registration Dates

• First Submitted: March 6, 2006
• First Submitted That Met QC Criteria: March 6, 2006
• First Posted (ESTIMATE): March 7, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Constipation; Randomized Controlled Trials; Medicine, Herbal; Medicine, Chinese Traditional
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: PID-001