Constipation, Functional Gastrointestinal Disorders
Conditions
Keywords
Functional Constipation, Chinese Herbal Medicine, MaZiRenWan, Hemp Seed Pill, Traditional Chinese Medicine, Herbal Medicine
Brief summary
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.
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.
Interventions
DRUGMaZiRenWan (MZRW)
MZRW granule dissolved in 150ml hot water (oral), 7.5g/sachet, twice daily
DRUGPlacebo
Placebo granule dissolved in 150ml hot water (oral), 7.5g/sachet, twice daily
Sponsors
Food and Health Bureau, Hong Kong
Purapharm International (Hk) Ltd.
Hong Kong Baptist University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder of Complete Spontaneous Bowel Movement (CSBM) | End of treatment (wk10) | 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
| Measure | Time frame | Description |
|---|---|---|
| Serum Glutamic Pyruvic Transaminase(SGPT) Level | Pre-treatment (Wk2) & Post-treatment (Wk10) | — |
| Serum Glutamic Oxaloacetic Transaminase (SGOT) | Pre-treatment (Wk2) & Post-treatment (Wk10) | — |
| Responder of Complete Spontaneous Bowel Movement (CSBM) | End of follow up (wk18) | 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 | Baseline(Wk1&2), Within treatment(Wk3-10) & Within follow-up(Wk11-18) | — |
| Blood Creatinine Level | Pre-treatment (Wk2) & Post-treatment (Wk10) | — |
| Changes on Individual Symptom Scores | Baseline(Wk2), Within treatment(Wk6), End of treatment(Wk10) & End of follow-up(Wk18) | It was a 7-point ordinal scale from 0=not at all to 6=very severe. |
| Global Symptoms Improvement | Wk 6, 10 & wk 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. |
| Success of Blinding | End of follow-up (Wk18) | The success of blinding was evaluated for both investigator and patients as to whether MZRW or placebo had been taken. |
| Blood Urea Level | Pre-treatment (Wk2) & Post-treatment (Wk10) | — |
| Complete Spontaneous Bowel Movement (CSBM) | Baseline(Wk1&2), Within treatment(Wk3-10), Within follow-up(Wk11-18) | — |
Countries
China
Participant flow
Recruitment details
All constipated patients (aged 18-65 years) who presented to the Chinese medicine clinics of the School of Chinese Medicine, Hong Kong Baptist University were referred. In total, 456 patients with constipation were screened from July 2008 to September 2009; of these 120 were randomized into MZRW or placebo group.
Pre-assignment details
Many patients were excluded because they did not fulfill the inclusion criteria or they met the exclusion criteria. The demographic data and baseline variables of participants were comparable among groups
Participants by arm
| Arm | Count |
|---|---|
| MaZiRenWan (MZRW) MZRW granule, 7.5g/sachet Patients were instructed to dissolve a sachet of granules in 150 ml of hot water; they took this solution orally twice daily for 8 weeks. | 60 |
| Placebo Placebo granule, 7.5g/sachet Patients were instructed to dissolve a sachet of granules in 150 ml of hot water; they took this solution orally twice daily for 8 weeks. | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Low compliance | 3 | 0 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | MaZiRenWan (MZRW) |
|---|---|---|---|
| Age, Continuous | 37.53 years STANDARD_DEVIATION 11.42 | 37.13 years STANDARD_DEVIATION 10.99 | 36.72 years STANDARD_DEVIATION 10.62 |
| Bowel movement | 3.31 movements per week STANDARD_DEVIATION 1.61 | 3.05 movements per week STANDARD_DEVIATION 1.46 | 2.79 movements per week STANDARD_DEVIATION 1.26 |
| Complete spontaneous bowel movement (CSBM) | 0.52 movements per week STANDARD_DEVIATION 0.69 | 0.42 movements per week STANDARD_DEVIATION 0.68 | 0.33 movements per week STANDARD_DEVIATION 0.66 |
| Duration of constipation | 15.25 years STANDARD_DEVIATION 10.82 | 14.38 years STANDARD_DEVIATION 10.39 | 13.50 years STANDARD_DEVIATION 9.96 |
| No. of days taking rescue therapy | 0.84 days per week STANDARD_DEVIATION 0.15 | 0.89 days per week STANDARD_DEVIATION 1.24 | 0.93 days per week STANDARD_DEVIATION 0.17 |
| Severity of constipation | 4.40 Units on a scale STANDARD_DEVIATION 0.1 | 4.43 Units on a scale STANDARD_DEVIATION 0.76 | 4.47 Units on a scale STANDARD_DEVIATION 0.102 |
| Sex: Female, Male Female | 57 Participants | 112 Participants | 55 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 60 | 7 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
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.
Time frame: End of treatment (wk10)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MaZiRenWan (MZRW) | Responder of Complete Spontaneous Bowel Movement (CSBM) | Responder | 26 participants |
| MaZiRenWan (MZRW) | Responder of Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 34 participants |
| Placebo | Responder of Complete Spontaneous Bowel Movement (CSBM) | Responder | 5 participants |
| Placebo | Responder of Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 55 participants |
p-value: <0.05Chi-squared
Secondary
Blood Creatinine Level
Time frame: Pre-treatment (Wk2) & Post-treatment (Wk10)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Blood Creatinine Level | Pre-treatment (Wk2) | 66.67 μmol/L | Standard Deviation 9.48 |
| MaZiRenWan (MZRW) | Blood Creatinine Level | Post-treatment (Wk10) | 66.90 μmol/L | Standard Deviation 9.2 |
| Placebo | Blood Creatinine Level | Pre-treatment (Wk2) | 66.05 μmol/L | Standard Deviation 7.91 |
| Placebo | Blood Creatinine Level | Post-treatment (Wk10) | 64.62 μmol/L | Standard Deviation 7.4 |
p-value: <0.05Paired-Samples T Test
Secondary
Blood Urea Level
Time frame: Pre-treatment (Wk2) & Post-treatment (Wk10)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Blood Urea Level | Pre-treatment (Wk2) | 3.87 mmol/L | Standard Deviation 1.03 |
| MaZiRenWan (MZRW) | Blood Urea Level | Post-treatment (Wk10) | 4.01 mmol/L | Standard Deviation 0.97 |
| Placebo | Blood Urea Level | Pre-treatment (Wk2) | 3.98 mmol/L | Standard Deviation 0.93 |
| Placebo | Blood Urea Level | Post-treatment (Wk10) | 4.24 mmol/L | Standard Deviation 1.11 |
p-value: <0.05Paired-samples t-test
Secondary
Bowel Movement
Time frame: Baseline(Wk1&2), Within treatment(Wk3-10) & Within follow-up(Wk11-18)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Bowel Movement | Baseline(Wk1&2) | 2.79 movements per week | Standard Deviation 1.26 |
| MaZiRenWan (MZRW) | Bowel Movement | Within treatment(Wk3-10) | 4.72 movements per week | Standard Deviation 2.37 |
| MaZiRenWan (MZRW) | Bowel Movement | Within follow-up(Wk11-18) | 3.65 movements per week | Standard Deviation 2.23 |
| Placebo | Bowel Movement | Baseline(Wk1&2) | 3.31 movements per week | Standard Deviation 1.61 |
| Placebo | Bowel Movement | Within treatment(Wk3-10) | 3.73 movements per week | Standard Deviation 1.54 |
| Placebo | Bowel Movement | Within follow-up(Wk11-18) | 3.61 movements per week | Standard Deviation 1.61 |
p-value: <0.05t-test, 2 sided
Secondary
Changes on Individual Symptom Scores
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Wk2), Within treatment(Wk6), End of treatment(Wk10) & End of follow-up(Wk18)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Passing of gas (Wk6) | 2.73 Units on a scale | Standard Deviation 1.52 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Severity of constipation (Baseline) | 4.47 Units on a scale | Standard Deviation 0.79 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Severity of constipation (Wk6) | 2.82 Units on a scale | Standard Deviation 1.52 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Severity of constipation (Wk10) | 2.93 Units on a scale | Standard Deviation 1.43 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Severity of constipation (Wk18) | 3.57 Units on a scale | Standard Deviation 1.47 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of straining (Baseline) | 4.20 Units on a scale | Standard Deviation 0.84 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of straining (Wk6) | 2.60 Units on a scale | Standard Deviation 1.43 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of straining (Wk10) | 2.55 Units on a scale | Standard Deviation 1.52 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of straining (Wk18) | 3.33 Units on a scale | Standard Deviation 1.28 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Incomplete of evacuation (Baseline) | 4.40 Units on a scale | Standard Deviation 1.12 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Incomplete of evacuation (Wk6) | 3.18 Units on a scale | Standard Deviation 1.4 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Incomplete of evacuation (Wk10) | 3.02 Units on a scale | Standard Deviation 1.51 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Incomplete of evacuation (Wk18) | 3.62 Units on a scale | Standard Deviation 1.29 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of bloating (Baseline) | 3.62 Units on a scale | Standard Deviation 1.3 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of bloating (Wk6) | 2.53 Units on a scale | Standard Deviation 1.68 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of bloating (Wk10) | 2.23 Units on a scale | Standard Deviation 1.65 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of bloating (Wk18) | 2.92 Units on a scale | Standard Deviation 1.67 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Baseline) | 1.98 Units on a scale | Standard Deviation 1.76 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Wk6) | 1.80 Units on a scale | Standard Deviation 1.6 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Wk10) | 1.22 Units on a scale | Standard Deviation 1.28 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Wk18) | 1.50 Units on a scale | Standard Deviation 1.54 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of nausea (Baseline) | 1.00 Units on a scale | Standard Deviation 1.54 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of nausea (Wk6) | 0.68 Units on a scale | Standard Deviation 1.21 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of nausea (Wk10) | 0.53 Units on a scale | Standard Deviation 0.97 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Sensation of nausea (Wk18) | 0.97 Units on a scale | Standard Deviation 1.48 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Passing of gas (Baseline) | 2.93 Units on a scale | Standard Deviation 1.75 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Passing of gas (Wk10) | 2.55 Units on a scale | Standard Deviation 1.43 |
| MaZiRenWan (MZRW) | Changes on Individual Symptom Scores | Passing of gas (Wk18) | 2.73 Units on a scale | Standard Deviation 1.46 |
| Placebo | Changes on Individual Symptom Scores | Sensation of bloating (Wk6) | 2.82 Units on a scale | Standard Deviation 1.76 |
| Placebo | Changes on Individual Symptom Scores | Passing of gas (Baseline) | 2.97 Units on a scale | Standard Deviation 1.67 |
| Placebo | Changes on Individual Symptom Scores | Severity of constipation (Baseline) | 4.40 Units on a scale | Standard Deviation 0.74 |
| Placebo | Changes on Individual Symptom Scores | Sensation of bloating (Wk10) | 2.70 Units on a scale | Standard Deviation 1.81 |
| Placebo | Changes on Individual Symptom Scores | Severity of constipation (Wk6) | 3.70 Units on a scale | Standard Deviation 1.49 |
| Placebo | Changes on Individual Symptom Scores | Sensation of nausea (Wk6) | 1.03 Units on a scale | Standard Deviation 1.57 |
| Placebo | Changes on Individual Symptom Scores | Severity of constipation (Wk10) | 3.47 Units on a scale | Standard Deviation 1.36 |
| Placebo | Changes on Individual Symptom Scores | Sensation of bloating (Wk18) | 2.65 Units on a scale | Standard Deviation 1.83 |
| Placebo | Changes on Individual Symptom Scores | Severity of constipation (Wk18) | 3.63 Units on a scale | Standard Deviation 1.39 |
| Placebo | Changes on Individual Symptom Scores | Passing of gas (Wk6) | 2.53 Units on a scale | Standard Deviation 1.7 |
| Placebo | Changes on Individual Symptom Scores | Sensation of straining (Baseline) | 3.82 Units on a scale | Standard Deviation 1.2 |
| Placebo | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Baseline) | 1.43 Units on a scale | Standard Deviation 1.58 |
| Placebo | Changes on Individual Symptom Scores | Sensation of straining (Wk6) | 3.12 Units on a scale | Standard Deviation 1.35 |
| Placebo | Changes on Individual Symptom Scores | Sensation of nausea (Wk10) | 0.78 Units on a scale | Standard Deviation 1.3 |
| Placebo | Changes on Individual Symptom Scores | Sensation of straining (Wk10) | 3.28 Units on a scale | Standard Deviation 1.46 |
| Placebo | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Wk6) | 1.12 Units on a scale | Standard Deviation 1.42 |
| Placebo | Changes on Individual Symptom Scores | Sensation of straining (Wk18) | 3.32 Units on a scale | Standard Deviation 1.37 |
| Placebo | Changes on Individual Symptom Scores | Passing of gas (Wk18) | 2.40 Units on a scale | Standard Deviation 1.6 |
| Placebo | Changes on Individual Symptom Scores | Incomplete of evacuation (Baseline) | 4.07 Units on a scale | Standard Deviation 1.22 |
| Placebo | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Wk10) | 1.07 Units on a scale | Standard Deviation 1.47 |
| Placebo | Changes on Individual Symptom Scores | Incomplete of evacuation (Wk6) | 3.47 Units on a scale | Standard Deviation 1.49 |
| Placebo | Changes on Individual Symptom Scores | Sensation of nausea (Wk18) | 0.73 Units on a scale | Standard Deviation 1.53 |
| Placebo | Changes on Individual Symptom Scores | Incomplete of evacuation (Wk10) | 3.45 Units on a scale | Standard Deviation 1.55 |
| Placebo | Changes on Individual Symptom Scores | Sensation of abdominal pain/cramping (Wk18) | 0.82 Units on a scale | Standard Deviation 1.35 |
| Placebo | Changes on Individual Symptom Scores | Incomplete of evacuation (Wk18) | 3.43 Units on a scale | Standard Deviation 1.57 |
| Placebo | Changes on Individual Symptom Scores | Passing of gas (Wk10) | 2.27 Units on a scale | Standard Deviation 1.68 |
| Placebo | Changes on Individual Symptom Scores | Sensation of bloating (Baseline) | 3.47 Units on a scale | Standard Deviation 1.33 |
| Placebo | Changes on Individual Symptom Scores | Sensation of nausea (Baseline) | 0.83 Units on a scale | Standard Deviation 1.45 |
p-value: <0.05t-test, 2 sided
Secondary
Complete Spontaneous Bowel Movement (CSBM)
Time frame: Baseline(Wk1&2), Within treatment(Wk3-10), Within follow-up(Wk11-18)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Complete Spontaneous Bowel Movement (CSBM) | Baseline (Wk1&2) | 0.33 movements per week | Standard Deviation 0.66 |
| MaZiRenWan (MZRW) | Complete Spontaneous Bowel Movement (CSBM) | Within treatment(Wk3-10) | 1.62 movements per week | Standard Deviation 1.98 |
| MaZiRenWan (MZRW) | Complete Spontaneous Bowel Movement (CSBM) | Within follow-up (Wk11-18) | 1.06 movements per week | Standard Deviation 1.67 |
| Placebo | Complete Spontaneous Bowel Movement (CSBM) | Baseline (Wk1&2) | 0.52 movements per week | Standard Deviation 0.69 |
| Placebo | Complete Spontaneous Bowel Movement (CSBM) | Within treatment(Wk3-10) | 0.72 movements per week | Standard Deviation 1.08 |
| Placebo | Complete Spontaneous Bowel Movement (CSBM) | Within follow-up (Wk11-18) | 0.75 movements per week | Standard Deviation 1.18 |
p-value: <0.05t-test, 2 sided
Secondary
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.
Time frame: Wk 6, 10 & wk 18
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Improved (Wk6) | 49 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Worse (Wk10) | 0 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Improved (Wk10) | 48 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Improved (Wk18) | 30 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Same (Wk6) | 11 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Same (Wk18) | 25 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Same (Wk10) | 12 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Worse (Wk18) | 5 participants |
| MaZiRenWan (MZRW) | Global Symptoms Improvement | Worse (Wk6) | 0 participants |
| Placebo | Global Symptoms Improvement | Worse (Wk18) | 2 participants |
| Placebo | Global Symptoms Improvement | Same (Wk6) | 27 participants |
| Placebo | Global Symptoms Improvement | Improved (Wk6) | 28 participants |
| Placebo | Global Symptoms Improvement | Worse (Wk6) | 5 participants |
| Placebo | Global Symptoms Improvement | Improved (Wk10) | 32 participants |
| Placebo | Global Symptoms Improvement | Same (Wk10) | 24 participants |
| Placebo | Global Symptoms Improvement | Worse (Wk10) | 4 participants |
| Placebo | Global Symptoms Improvement | Improved (Wk18) | 31 participants |
| Placebo | Global Symptoms Improvement | Same (Wk18) | 27 participants |
p-value: <0.05Chi-squared
Secondary
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.
Time frame: End of follow up (wk18)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MaZiRenWan (MZRW) | Responder of Complete Spontaneous Bowel Movement (CSBM) | Responder | 18 participants |
| MaZiRenWan (MZRW) | Responder of Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 42 participants |
| Placebo | Responder of Complete Spontaneous Bowel Movement (CSBM) | Responder | 9 participants |
| Placebo | Responder of Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 51 participants |
p-value: <0.05Chi-squared
Secondary
Serum Glutamic Oxaloacetic Transaminase (SGOT)
Time frame: Pre-treatment (Wk2) & Post-treatment (Wk10)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Serum Glutamic Oxaloacetic Transaminase (SGOT) | Pre-treatment (Wk2) | 17.82 U/L | Standard Deviation 4.05 |
| MaZiRenWan (MZRW) | Serum Glutamic Oxaloacetic Transaminase (SGOT) | Post-treatment (Wk10) | 17.20 U/L | Standard Deviation 3.45 |
| Placebo | Serum Glutamic Oxaloacetic Transaminase (SGOT) | Pre-treatment (Wk2) | 17.77 U/L | Standard Deviation 3.91 |
| Placebo | Serum Glutamic Oxaloacetic Transaminase (SGOT) | Post-treatment (Wk10) | 17.12 U/L | Standard Deviation 4.27 |
p-value: <0.05Paired-Samples T Test
Secondary
Serum Glutamic Pyruvic Transaminase(SGPT) Level
Time frame: Pre-treatment (Wk2) & Post-treatment (Wk10)
Population: Statistical analysis was performed on the population being randomized and receiving allocated intervention. Missing values were imputed by the method of last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MaZiRenWan (MZRW) | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Pre-treatment (Wk2) | 15.82 U/L | Standard Deviation 7.81 |
| MaZiRenWan (MZRW) | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Post-treatment (Wk10) | 14.70 U/L | Standard Deviation 5.5 |
| Placebo | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Pre-treatment (Wk2) | 14.05 U/L | Standard Deviation 4.87 |
| Placebo | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Post-treatment (Wk10) | 13.68 U/L | Standard Deviation 4.55 |
p-value: <0.05Paired-Samples T Test
Secondary
Success of Blinding
The success of blinding was evaluated for both investigator and patients as to whether MZRW or placebo had been taken.
Time frame: End of follow-up (Wk18)
Population: Only for subjects attended the last follow-up visit on Wk 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MaZiRenWan (MZRW) | Success of Blinding | Subjects with correct guessing | 32 participants |
| MaZiRenWan (MZRW) | Success of Blinding | Investigator with correct guessing | 42 participants |
| Placebo | Success of Blinding | Subjects with correct guessing | 16 participants |
| Placebo | Success of Blinding | Investigator with correct guessing | 27 participants |
p-value: 0simple percentage