A Double-blinded,Double-dummy Clinical Trial of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation

Phase 2

Completed

• Conditions: Gastrointestinal Disorders; Functional Constipation
• Interventions: Drug: MZRW; Drug: Senna; Drug: placebo

• Registration Number: NCT01695850
• Lead Sponsor: Hong Kong Baptist University

Brief Summary

The objective of this study is to evaluate the efficacy and safety of a Chinese herbal proprietary medicine, MaZiRenWan (MZRW), by comparing with stimulant laxative western medicine (WM), senna, and placebo for patients with functional constipation (FC) in excessive TCM syndrome.

Detailed Description

Functional constipation (FC) is a common clinical complaint. Despite the effectiveness of MaZiRenWan (MZRW) for alleviating FC symptoms has been proofed in the previous study.Given the results of the dose determination study and placebo-controlled study of MZRW, we hypothesize that MZRW is more useful than senna (senokot), a commonly used WM drug for constipation, for FC patients in excessive TCM syndrome.This is a prospective, double-blind, double dummy, randomized, controlled trial. After a 2-week run-in, eligible FC patients (Rome III) in excessive TCM syndrome will randomly be assigned to CHM arm (MZRW and WM placebo), WM arm (senna and CHM placebo) or placebo arm (CHM placebo and WM placebo). Patients will undergo an 8-week treatment and an 8-week follow-up.

Study Timeline

• Study First Submitted: 2012-09-27
• Study First Submitted QC: 2012-09-27
• Study First Posted: 2012-09-28
• Study Start: 2013-06
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-10
• Last Update Posted: 2020-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 291

Inclusion Criteria

• either gender aged 18 to 65 years
• have FC diagnosed as Rome III criterial
• have diagnosis of Excessive Constipation according to the TCM theory
• complete spontaneous bowel movement (CSBM) ≦2times/w
• severity of constipation≧3pts (7 pts scale from 0 to 6pts) and the overall scoring of constipation-related symptoms≧6pts (6items in 7pts scale) for self symptom assessment in the run-in period
• normal colonic evaluation (colonoscopy or barium enema) within 12 months
• 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 diseases (i.e. cancer and acute present asthma)
• allergy to CHM (i.e. G6PD deficiency), senna and tartrazine
• pregnancy or breast-feeding
• psychiatric or addictive disorders

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MZRW	placebo	MZRW is composed of Fructus Cannabis (HuoMaRen), Radix et Rhizoma Rhei (DaHuang), Radix Paeoniae Alba (BaiShao), Semen Armeniacae Amarum (KuXingRen), Fructus Aurantii Immaturus (ZhiShi) and Cortex Magnoliae Officinalis (HouPo).
MZRW	MZRW	MZRW is composed of Fructus Cannabis (HuoMaRen), Radix et Rhizoma Rhei (DaHuang), Radix Paeoniae Alba (BaiShao), Semen Armeniacae Amarum (KuXingRen), Fructus Aurantii Immaturus (ZhiShi) and Cortex Magnoliae Officinalis (HouPo).
Senna	placebo	Senna is a stimulant laxative which facilitates the passage of stools by altering intestinal electrolyte transport and increasing intestinal motor activity.
Placebo	placebo	Placebo MZRW and Placebo Senna
Senna	Senna	Senna is a stimulant laxative which facilitates the passage of stools by altering intestinal electrolyte transport and increasing intestinal motor activity.

Primary Outcome Measures

Name	Time	Method
the responder rate for CSBM during the treatment period	8 weeks	a clinically meaningful endpoint by combining an objective measure (number of bowel movement) with a subjective measure (feelings of patients as to completeness of defecation,Patients with a mean increase of ≧1 complete spontaneous bowel movement(CSBM)/wk compared with the baseline(wk1-2) will be defined as responders

Secondary Outcome Measures

Name	Time	Method
the responder rate for CSBM during the follow-up period	8 weeks	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
Individual assessment of constipation and related symptoms	18 weeks	severity of constipation, sensation of straining, incomplete evacuation, bloating, abdominal pain / cramping, nausea, and passing of gas) was recorded using a 7-point ordinal scale (0 = not at all and 6 = very severe
the changes of colonic transit time	18 weeks	It is estimated by using a commercially available radio-opaque Sitzmarks capsule (Konsyl Pharmaceuticals, US). Each gelatine capsule contained 24 barium sulphate embedded polyvinyl chloride markers measuring 1mmx4.5mm. Plain radiographs of the abdomen will be obtained after the swallow of capsule for five days (120 hours) before and after 8 weeks treatment period.
Global symptom assessment	18 weeks	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	18 weeks	the success of blinding is evaluated for both investigator and patients as to whether CHM, WM or placebo had been taken
safety profiles	18 weeks	Assessed by determining the important adverse events reported in the participants ' diaries, follow-up interviews,and clinical laboratory evaluationse.g., liver and renal function.

Trial Locations

Locations (1)

School of Chinese Medicine, Hong Kong Baptist University; 🇨🇳 Hong Kong, Hong Kong, China