A Dose Determination Study of Chinese Herbal Medicine for Functional Constipation

Phase 2

Completed

Conditions: Constipation

Interventions: Drug: MaZiRenWan (MZRW) Median dose
Drug: MaZiRenWan (MZRW) Low dose
Drug: MaZiRenWan (MZRW) High dose

Registration Number: NCT00299975

Lead Sponsor: Hong Kong Baptist University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 97

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MaZiRenWan (MZRW) Median dose	MaZiRenWan (MZRW) Median dose	MaZiRenWan (MZRW) Median dose 5.0g sachet by mouth, twice daily for 8 weeks
MaZiRenWan (MZRW) Low dose	MaZiRenWan (MZRW) Low dose	MaZiRenWan (MZRW) Low dose 2.5g sachet by mouth, twice daily for 8 weeks
MaZiRenWan (MZRW) High dose	MaZiRenWan (MZRW) High dose	MaZiRenWan (MZRW) High dose 7.5g sachet by mouth, twice daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
Responder for Complete Spontaneous Bowel Movement (CSBM)	Week3-10	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.

Secondary Outcome Measures

Name	Time	Method
Responder for Complete Spontaneous Bowel Movement (CSBM)	Week11-18	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.
Bowel Movement	Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18)
Global Symptoms Improvement	Week6, 10 & 18	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.
Sensation of Straining	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)	It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Blood Urea Level	Pre-treatment(Week2) & Post-treatment(Week10)
Complete Spontaneous Bowel Movement (CSBM)	Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18)	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.
Severity of Constipation	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)	It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Incomplete of Evacuation	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)	It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Sensation of Bloating	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)	It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Sensation of Abdominal Pain/Cramping	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)	It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Passing of Gas	Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)	It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Adverse Effects (e.g. Renal and Liver Function Tests)	pre-treatment & post-treatment
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)