Constipation
Conditions
Keywords
Randomized Controlled Trials, Medicine, Chinese Traditional, Medicine, Herbal, Constipation
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.
Interventions
DRUGMaZiRenWan (MZRW) Low dose
Dissolved MaZiRenWan (MZRW) granule (2.5g/sachet) in 150 ml hot water, take orally twice daily for 8 weeks
DRUGMaZiRenWan (MZRW) Median dose
Dissolved MaZiRenWan (MZRW) granule (5.0g/sachet) in 150 ml hot water, take orally twice daily for 8 weeks
DRUGMaZiRenWan (MZRW) High dose
Dissolved MaZiRenWan (MZRW) granule (7.5g/sachet) in 150 ml hot water, take orally twice daily for 8 weeks
Sponsors
Hong Kong Baptist University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Bowel Movement | Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18) | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 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) | — |
| 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. |
Countries
China
Participant flow
Recruitment details
All constipated patients (aged 18-65) who presented to the Chinese Medicine Clinics of School of Chinese Medicine, Hong Kong Baptist University from October 2006 to May 2007 were refered.
Pre-assignment details
177 patients were screened; of these 80 patients were excluded due to not meeting inclusion criteria (68 cases), refused to participate (6 cases) and lost to follow up (6 cases).
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Group MaZiRenWan (MZRW) 2.5g/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. | 32 |
| Median Dose Group MaZiRenWan (MZRW) 5.0g/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. | 32 |
| High Dose Group MaZiRenWan (MZRW) 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. | 32 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Low Dose Group | Median Dose Group | High Dose Group | Total |
|---|---|---|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 9.8 | 38.8 years STANDARD_DEVIATION 9.9 | 36.1 years STANDARD_DEVIATION 9.2 | 36.8 years STANDARD_DEVIATION 9.6 |
| Bowel Movement | 3.6 movements per week STANDARD_DEVIATION 1.5 | 3.1 movements per week STANDARD_DEVIATION 1.4 | 4.7 movements per week STANDARD_DEVIATION 4.1 | 3.8 movements per week STANDARD_DEVIATION 2.7 |
| Complete Spontaneous Bowel Movement (CSBM) | 0.5 movements per week STANDARD_DEVIATION 0.6 | 0.5 movements per week STANDARD_DEVIATION 0.7 | 0.5 movements per week STANDARD_DEVIATION 0.7 | 0.5 movements per week STANDARD_DEVIATION 0.7 |
| Duration of constipation | 10.9 years STANDARD_DEVIATION 8.5 | 13.7 years STANDARD_DEVIATION 10 | 15.0 years STANDARD_DEVIATION 10.9 | 13.2 years STANDARD_DEVIATION 9.9 |
| No. of days taking rescue therapy | 1.7 days per week STANDARD_DEVIATION 2.8 | 2.4 days per week STANDARD_DEVIATION 3.3 | 2.2 days per week STANDARD_DEVIATION 3.2 | 2.1 days per week STANDARD_DEVIATION 3.1 |
| Severity of Constipation | 4.2 Units on a scale STANDARD_DEVIATION 1.1 | 4.1 Units on a scale STANDARD_DEVIATION 1.3 | 4.3 Units on a scale STANDARD_DEVIATION 1.5 | 4.2 Units on a scale STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 30 Participants | 27 Participants | 30 Participants | 87 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 32 | 10 / 32 | 14 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
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.
Time frame: Week3-10
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) |
|---|---|---|---|
| Low Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Responder | 10 participants |
| Low Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 22 participants |
| Median Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Responder | 14 participants |
| Median Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 18 participants |
| High Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Responder | 17 participants |
| High Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 15 participants |
p-value: <0.05Chi-squared
Secondary
Adverse Effects (e.g. Renal and Liver Function Tests)
Time frame: pre-treatment & post-treatment
Secondary
Blood Creatinine Level
Time frame: Pre-treatment(Week2) & Post-treatment(Week10)
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 |
|---|---|---|---|---|
| Low Dose Group | Blood Creatinine Level | Week2 | 58.81 μmol/L | Standard Deviation 13.22 |
| Low Dose Group | Blood Creatinine Level | Week10 | 58.81 μmol/L | Standard Deviation 10.17 |
| Median Dose Group | Blood Creatinine Level | Week2 | 58.00 μmol/L | Standard Deviation 15.23 |
| Median Dose Group | Blood Creatinine Level | Week10 | 60.06 μmol/L | Standard Deviation 17.27 |
| High Dose Group | Blood Creatinine Level | Week2 | 57.38 μmol/L | Standard Deviation 12.46 |
| High Dose Group | Blood Creatinine Level | Week10 | 58.09 μmol/L | Standard Deviation 13.74 |
p-value: <0.05Paired-Samples T Test
Secondary
Blood Urea Level
Time frame: Pre-treatment(Week2) & Post-treatment(Week10)
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 |
|---|---|---|---|---|
| Low Dose Group | Blood Urea Level | Week2 | 4.68 mmol/L | Standard Deviation 1.23 |
| Low Dose Group | Blood Urea Level | Week10 | 4.40 mmol/L | Standard Deviation 1.18 |
| Median Dose Group | Blood Urea Level | Week2 | 4.54 mmol/L | Standard Deviation 1.12 |
| Median Dose Group | Blood Urea Level | Week10 | 4.41 mmol/L | Standard Deviation 0.94 |
| High Dose Group | Blood Urea Level | Week2 | 4.31 mmol/L | Standard Deviation 1.25 |
| High Dose Group | Blood Urea Level | Week10 | 4.30 mmol/L | Standard Deviation 1.26 |
p-value: <0.05Paired-Samples T Test
Secondary
Bowel Movement
Time frame: Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18)
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 |
|---|---|---|---|---|
| Low Dose Group | Bowel Movement | Wk3-10 | 4.2 movements per week | Standard Deviation 1.7 |
| Low Dose Group | Bowel Movement | Wk1-2 | 3.6 movements per week | Standard Deviation 1.5 |
| Low Dose Group | Bowel Movement | Wk11-18 | 3.9 movements per week | Standard Deviation 1.6 |
| Median Dose Group | Bowel Movement | Wk3-10 | 4.8 movements per week | Standard Deviation 1.8 |
| Median Dose Group | Bowel Movement | Wk1-2 | 3.1 movements per week | Standard Deviation 1.4 |
| Median Dose Group | Bowel Movement | Wk11-18 | 3.5 movements per week | Standard Deviation 1.2 |
| High Dose Group | Bowel Movement | Wk1-2 | 4.7 movements per week | Standard Deviation 4.1 |
| High Dose Group | Bowel Movement | Wk11-18 | 5.2 movements per week | Standard Deviation 4.2 |
| High Dose Group | Bowel Movement | Wk3-10 | 6.5 movements per week | Standard Deviation 5.5 |
p-value: <0.05ANOVA
Secondary
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.
Time frame: Baseline(Week1-2), Within treatment(Week3-10) & Within follow-up(Week11-18)
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 |
|---|---|---|---|---|
| Low Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week3-10 | 1.4 movements per week | Standard Deviation 1.4 |
| Low Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week1-2 | 0.5 movements per week | Standard Deviation 0.6 |
| Low Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week11-18 | 1.4 movements per week | Standard Deviation 1.5 |
| Median Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week3-10 | 1.6 movements per week | Standard Deviation 1.5 |
| Median Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week1-2 | 0.5 movements per week | Standard Deviation 0.7 |
| Median Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week11-18 | 1.0 movements per week | Standard Deviation 1.2 |
| High Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week1-2 | 0.5 movements per week | Standard Deviation 0.7 |
| High Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week11-18 | 1.3 movements per week | Standard Deviation 1.6 |
| High Dose Group | Complete Spontaneous Bowel Movement (CSBM) | Week3-10 | 2.0 movements per week | Standard Deviation 2.1 |
p-value: <0.05ANOVA
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: Week6, 10 & 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) |
|---|---|---|---|
| Low Dose Group | Global Symptoms Improvement | Week10-Improved | 20 participants |
| Low Dose Group | Global Symptoms Improvement | Week18-Worse | 1 participants |
| Low Dose Group | Global Symptoms Improvement | Week10-Worse | 2 participants |
| Low Dose Group | Global Symptoms Improvement | Week10-Same | 10 participants |
| Low Dose Group | Global Symptoms Improvement | Week6-Improved | 25 participants |
| Low Dose Group | Global Symptoms Improvement | Week18-Same | 11 participants |
| Low Dose Group | Global Symptoms Improvement | Week6-Worse | 3 participants |
| Low Dose Group | Global Symptoms Improvement | Week6-Same | 4 participants |
| Low Dose Group | Global Symptoms Improvement | Week18-Improved | 20 participants |
| Median Dose Group | Global Symptoms Improvement | Week10-Same | 5 participants |
| Median Dose Group | Global Symptoms Improvement | Week6-Improved | 24 participants |
| Median Dose Group | Global Symptoms Improvement | Week6-Same | 7 participants |
| Median Dose Group | Global Symptoms Improvement | Week6-Worse | 1 participants |
| Median Dose Group | Global Symptoms Improvement | Week10-Improved | 27 participants |
| Median Dose Group | Global Symptoms Improvement | Week10-Worse | 0 participants |
| Median Dose Group | Global Symptoms Improvement | Week18-Improved | 14 participants |
| Median Dose Group | Global Symptoms Improvement | Week18-Same | 14 participants |
| Median Dose Group | Global Symptoms Improvement | Week18-Worse | 4 participants |
| High Dose Group | Global Symptoms Improvement | Week6-Worse | 2 participants |
| High Dose Group | Global Symptoms Improvement | Week6-Improved | 26 participants |
| High Dose Group | Global Symptoms Improvement | Week18-Improved | 20 participants |
| High Dose Group | Global Symptoms Improvement | Week6-Same | 4 participants |
| High Dose Group | Global Symptoms Improvement | Week18-Worse | 0 participants |
| High Dose Group | Global Symptoms Improvement | Week10-Same | 6 participants |
| High Dose Group | Global Symptoms Improvement | Week10-Improved | 24 participants |
| High Dose Group | Global Symptoms Improvement | Week18-Same | 12 participants |
| High Dose Group | Global Symptoms Improvement | Week10-Worse | 2 participants |
p-value: <0.05Chi-squared
Secondary
Incomplete of Evacuation
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
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 |
|---|---|---|---|---|
| Low Dose Group | Incomplete of Evacuation | Week2 | 4.53 Units on a scale | Standard Deviation 1.41 |
| Low Dose Group | Incomplete of Evacuation | Week6 | 2.81 Units on a scale | Standard Deviation 1.87 |
| Low Dose Group | Incomplete of Evacuation | Week10 | 2.69 Units on a scale | Standard Deviation 1.91 |
| Low Dose Group | Incomplete of Evacuation | Week18 | 3.00 Units on a scale | Standard Deviation 1.83 |
| Median Dose Group | Incomplete of Evacuation | Week18 | 2.94 Units on a scale | Standard Deviation 1.7 |
| Median Dose Group | Incomplete of Evacuation | Week2 | 3.5 Units on a scale | Standard Deviation 1.63 |
| Median Dose Group | Incomplete of Evacuation | Week10 | 2.63 Units on a scale | Standard Deviation 1.64 |
| Median Dose Group | Incomplete of Evacuation | Week6 | 2.59 Units on a scale | Standard Deviation 1.66 |
| High Dose Group | Incomplete of Evacuation | Week18 | 2.50 Units on a scale | Standard Deviation 1.67 |
| High Dose Group | Incomplete of Evacuation | Week6 | 2.59 Units on a scale | Standard Deviation 1.58 |
| High Dose Group | Incomplete of Evacuation | Week10 | 2.66 Units on a scale | Standard Deviation 1.77 |
| High Dose Group | Incomplete of Evacuation | Week2 | 3.97 Units on a scale | Standard Deviation 1.26 |
p-value: <0.05ANOVA
Secondary
Passing of Gas
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
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 |
|---|---|---|---|---|
| Low Dose Group | Passing of Gas | Week10 | 1.38 Units on a scale | Standard Deviation 1.24 |
| Low Dose Group | Passing of Gas | Week2 | 2.37 Units on a scale | Standard Deviation 1.7 |
| Low Dose Group | Passing of Gas | Week18 | 1.25 Units on a scale | Standard Deviation 1.19 |
| Low Dose Group | Passing of Gas | Week6 | 2.03 Units on a scale | Standard Deviation 1.49 |
| Median Dose Group | Passing of Gas | Week10 | 2.06 Units on a scale | Standard Deviation 1.27 |
| Median Dose Group | Passing of Gas | Week6 | 1.97 Units on a scale | Standard Deviation 1.49 |
| Median Dose Group | Passing of Gas | Week2 | 2.59 Units on a scale | Standard Deviation 1.43 |
| Median Dose Group | Passing of Gas | Week18 | 2.19 Units on a scale | Standard Deviation 1.36 |
| High Dose Group | Passing of Gas | Week18 | 2.53 Units on a scale | Standard Deviation 1.63 |
| High Dose Group | Passing of Gas | Week2 | 3.34 Units on a scale | Standard Deviation 1.29 |
| High Dose Group | Passing of Gas | Week6 | 2.44 Units on a scale | Standard Deviation 1.46 |
| High Dose Group | Passing of Gas | Week10 | 2.38 Units on a scale | Standard Deviation 1.56 |
p-value: <0.05ANOVA
Secondary
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.
Time frame: Week11-18
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) |
|---|---|---|---|
| Low Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Responder | 9 participants |
| Low Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 23 participants |
| Median Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Responder | 10 participants |
| Median Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 22 participants |
| High Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Responder | 11 participants |
| High Dose Group | Responder for Complete Spontaneous Bowel Movement (CSBM) | Non-responder | 21 participants |
p-value: <0.05Chi-squared
Secondary
Sensation of Abdominal Pain/Cramping
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
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 |
|---|---|---|---|---|
| Low Dose Group | Sensation of Abdominal Pain/Cramping | Week2 | 1.00 Units on a scale | Standard Deviation 1.24 |
| Low Dose Group | Sensation of Abdominal Pain/Cramping | Week6 | 1.00 Units on a scale | Standard Deviation 1.27 |
| Low Dose Group | Sensation of Abdominal Pain/Cramping | Week10 | 0.41 Units on a scale | Standard Deviation 0.98 |
| Low Dose Group | Sensation of Abdominal Pain/Cramping | Week18 | 0.47 Units on a scale | Standard Deviation 0.92 |
| Median Dose Group | Sensation of Abdominal Pain/Cramping | Week18 | 0.91 Units on a scale | Standard Deviation 1.25 |
| Median Dose Group | Sensation of Abdominal Pain/Cramping | Week2 | 1.12 Units on a scale | Standard Deviation 1.29 |
| Median Dose Group | Sensation of Abdominal Pain/Cramping | Week10 | 1.09 Units on a scale | Standard Deviation 1.2 |
| Median Dose Group | Sensation of Abdominal Pain/Cramping | Week6 | 1.03 Units on a scale | Standard Deviation 1.31 |
| High Dose Group | Sensation of Abdominal Pain/Cramping | Week18 | 0.84 Units on a scale | Standard Deviation 1.19 |
| High Dose Group | Sensation of Abdominal Pain/Cramping | Week6 | 1.50 Units on a scale | Standard Deviation 1.48 |
| High Dose Group | Sensation of Abdominal Pain/Cramping | Week10 | 1.47 Units on a scale | Standard Deviation 1.74 |
| High Dose Group | Sensation of Abdominal Pain/Cramping | Week2 | 1.59 Units on a scale | Standard Deviation 1.68 |
p-value: <0.05ANOVA
Secondary
Sensation of Bloating
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
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 |
|---|---|---|---|---|
| Low Dose Group | Sensation of Bloating | Week6 | 2.03 Units on a scale | Standard Deviation 1.91 |
| Low Dose Group | Sensation of Bloating | Week10 | 1.78 Units on a scale | Standard Deviation 1.85 |
| Low Dose Group | Sensation of Bloating | Week18 | 1.91 Units on a scale | Standard Deviation 1.69 |
| Low Dose Group | Sensation of Bloating | Week2 | 2.53 Units on a scale | Standard Deviation 1.9 |
| Median Dose Group | Sensation of Bloating | Week2 | 2.75 Units on a scale | Standard Deviation 1.92 |
| Median Dose Group | Sensation of Bloating | Week6 | 1.84 Units on a scale | Standard Deviation 1.63 |
| Median Dose Group | Sensation of Bloating | Week18 | 2.19 Units on a scale | Standard Deviation 1.86 |
| Median Dose Group | Sensation of Bloating | Week10 | 1.63 Units on a scale | Standard Deviation 1.66 |
| High Dose Group | Sensation of Bloating | Week18 | 1.94 Units on a scale | Standard Deviation 1.76 |
| High Dose Group | Sensation of Bloating | Week10 | 1.75 Units on a scale | Standard Deviation 1.92 |
| High Dose Group | Sensation of Bloating | Week2 | 3.28 Units on a scale | Standard Deviation 1.87 |
| High Dose Group | Sensation of Bloating | Week6 | 1.91 Units on a scale | Standard Deviation 1.82 |
p-value: <0.05ANOVA
Secondary
Sensation of Straining
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
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 |
|---|---|---|---|---|
| Low Dose Group | Sensation of Straining | Week10 | 2.56 Units on a scale | Standard Deviation 1.92 |
| Low Dose Group | Sensation of Straining | Week2 | 4.03 Units on a scale | Standard Deviation 1.06 |
| Low Dose Group | Sensation of Straining | Week18 | 2.69 Units on a scale | Standard Deviation 1.86 |
| Low Dose Group | Sensation of Straining | Week6 | 2.62 Units on a scale | Standard Deviation 1.79 |
| Median Dose Group | Sensation of Straining | Week10 | 2.06 Units on a scale | Standard Deviation 1.7 |
| Median Dose Group | Sensation of Straining | Week6 | 1.84 Units on a scale | Standard Deviation 1.73 |
| Median Dose Group | Sensation of Straining | Week18 | 2.78 Units on a scale | Standard Deviation 1.88 |
| Median Dose Group | Sensation of Straining | Week2 | 3.53 Units on a scale | Standard Deviation 1.61 |
| High Dose Group | Sensation of Straining | Week18 | 2.34 Units on a scale | Standard Deviation 1.6 |
| High Dose Group | Sensation of Straining | Week2 | 3.78 Units on a scale | Standard Deviation 1.6 |
| High Dose Group | Sensation of Straining | Week6 | 2.16 Units on a scale | Standard Deviation 1.61 |
| High Dose Group | Sensation of Straining | Week10 | 1.94 Units on a scale | Standard Deviation 1.74 |
p-value: <0.05ANOVA
Secondary
Serum Glutamic Oxaloacetic Transaminase(SGOT) Level
Time frame: Pre-treatment(Week2) & Post-treatment(Week10)
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 |
|---|---|---|---|---|
| Low Dose Group | Serum Glutamic Oxaloacetic Transaminase(SGOT) Level | Week2 | 18.50 U/L | Standard Deviation 5.01 |
| Low Dose Group | Serum Glutamic Oxaloacetic Transaminase(SGOT) Level | Week10 | 18.69 U/L | Standard Deviation 5.04 |
| Median Dose Group | Serum Glutamic Oxaloacetic Transaminase(SGOT) Level | Week2 | 18.28 U/L | Standard Deviation 4.3 |
| Median Dose Group | Serum Glutamic Oxaloacetic Transaminase(SGOT) Level | Week10 | 19.09 U/L | Standard Deviation 5.08 |
| High Dose Group | Serum Glutamic Oxaloacetic Transaminase(SGOT) Level | Week2 | 19.44 U/L | Standard Deviation 5.29 |
| High Dose Group | Serum Glutamic Oxaloacetic Transaminase(SGOT) Level | Week10 | 19.09 U/L | Standard Deviation 5.57 |
p-value: <0.05Paired-Samples T Test
Secondary
Serum Glutamic Pyruvic Transaminase(SGPT) Level
Time frame: Pre-treatment(Week2) & Post-treatment(Week10)
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 |
|---|---|---|---|---|
| Low Dose Group | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Week2 | 32.38 U/L | Standard Deviation 6.95 |
| Low Dose Group | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Week10 | 33.44 U/L | Standard Deviation 8.99 |
| Median Dose Group | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Week2 | 32.78 U/L | Standard Deviation 5.33 |
| Median Dose Group | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Week10 | 34.06 U/L | Standard Deviation 6.67 |
| High Dose Group | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Week2 | 34.06 U/L | Standard Deviation 9.01 |
| High Dose Group | Serum Glutamic Pyruvic Transaminase(SGPT) Level | Week10 | 34.16 U/L | Standard Deviation 7.32 |
p-value: <0.05Paired-Samples T Test
Secondary
Severity of Constipation
It was a 7-point ordinal scale from 0=not at all to 6=very severe.
Time frame: Baseline(Week2), Within treatment(Week6), End of treatment(Week10) & End of follow-up(Week18)
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 |
|---|---|---|---|---|
| Low Dose Group | Severity of Constipation | Week2 | 4.22 Units on a scale | Standard Deviation 1.07 |
| Low Dose Group | Severity of Constipation | Week6 | 2.72 Units on a scale | Standard Deviation 1.87 |
| Low Dose Group | Severity of Constipation | Week10 | 2.62 Units on a scale | Standard Deviation 1.88 |
| Low Dose Group | Severity of Constipation | Week18 | 3.03 Units on a scale | Standard Deviation 1.91 |
| Median Dose Group | Severity of Constipation | Week18 | 2.91 Units on a scale | Standard Deviation 1.92 |
| Median Dose Group | Severity of Constipation | Week2 | 4.06 Units on a scale | Standard Deviation 1.32 |
| Median Dose Group | Severity of Constipation | Week10 | 2.06 Units on a scale | Standard Deviation 1.76 |
| Median Dose Group | Severity of Constipation | Week6 | 2.03 Units on a scale | Standard Deviation 1.84 |
| High Dose Group | Severity of Constipation | Week18 | 2.38 Units on a scale | Standard Deviation 1.74 |
| High Dose Group | Severity of Constipation | Week6 | 2.03 Units on a scale | Standard Deviation 1.75 |
| High Dose Group | Severity of Constipation | Week10 | 2.06 Units on a scale | Standard Deviation 1.81 |
| High Dose Group | Severity of Constipation | Week2 | 4.25 Units on a scale | Standard Deviation 1.46 |
p-value: <0.05ANOVA