Constipation
Conditions
Keywords
Acupuncture, Functional constipation
Brief summary
The purpose of this study is to re-evaluate the therapeutic superiority and safety of acupuncture treatment using high quality and large sampled clinical research. The investigators want to provide a preferred treatment protocol, which is effective, safe, and easy to use in clinical practice. This research also clarifies that the insertion depth is a key factor in the therapeutic effect of acupuncture. The results of the study will help promote the development of the standardization of acupuncture.
Detailed description
Functional constipation is a high morbidity disease. The life-long treatment of functional constipation can seriously impact a patient's quality of life. At present, one of the most frequently used treatment is catharsis, which deals with the symptom. There are three main problems with catharsis. First, there are no long-lasting effects once the patient stops taking medication. Second, there are many side effects, including abdominal pain with defecation and diarrhea. Third, long-term use of irritant laxatives will not only make the constipation become refractory and complex; but also, this type of medicine can harm the enteric nervous system, cause melanosis coli, or even carcinoma of colon. Therefore, a therapy that is safe with minimal side effects and good short-term and long-term effects is urgently needed in functional constipation treatment. Clinical practice shows that acupuncture may meets this need to some extent. The acupuncture therapy is safe and effective and the therapeutic effects are still present several months after the treatment has been completed.
Interventions
OTHERdeep needling
Huatuo brand needle (0.35×75mm), LH202H electric stimulator, parameter is constant wave, 2/15Hz, and current intensity is the abdominal muscles shiver slightly and the patient feels trivial pain. Once a day, five times a week, four weeks.
DRUGLactulose
20-30ml, once a day before breakfast, for the whole study except the run-in period
OTHERshallow needling
Huatuo brand needle (0.30×25mm). The usage of EA apparatus and treatment course were the same as deep needling group.
Sponsors
Ministry of Science and Technology of the People´s Republic of China
Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* meeting the diagnosis of Rome III criteria; * aged from 18 to 75 years old; * no use of medicine for constipation about 2 weeks before the enrollment, no acupuncture treatment for constipation in the previous 3 months, and never joined any other trial in progress in the previous 3 months; * volunteered to join this trial and signed the informed consent form
Exclusion criteria
* irritable bowel syndrome, organic constipation or secondary constipation caused by endocrine, metabolic, nervous, postoperative diseases, or by drugs; * constipation with serious cardiovascular, hepatic or renal diseases, cognitive dysfunction, aphasia, mental disorders, or illness which affects the cooperation for examination and treatment; * women in gestation or lactation period; * abdominal aortic aneurysm or hepatosplenomegaly, etc.; * blood coagulation disorders or using anticoagulants regularly such as Warfarin and Heparin; * cardiac pacemaker carrier.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Mean Weekly Spontaneous Bowel Movements | over 4-week treatment, at the 4th week of follow-up, at the 12th week of follow-up | Spontaneous bowel movements per week were assessed every week during 4 weeks of treatment according to patients' diaries. Weekly spontaneous bowel movements were also assessed at the 4th and 12th week of follow-up according to patients' diaries. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Mean Value of Incomplete Evacuation | over 4 weeks of treatment | Score of incomplete evacuation was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of incomplete evacuation over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. |
| Change of Mean Value of Stool Consistency | over 4 weeks of treatment | Score of stool consistency was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of stool consistency over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. We corrected the mean value of stool consistency by covariance because the data had significant difference among three groups at baseline. |
| Change of Mean Value of Abdominal Distention | over 4 weeks of treatment | Score of abdominal distention was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of abdominal distention over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. We corrected the mean value of abdominal distention by covariance because the data had significant difference among three groups at baseline. |
| Change of Mean Value of Straining During Defecating | over 4 weeks of treatment | Score of straining during defecating was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of straining during defecating over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. We corrected the mean value of straining during defecating by covariance because the data had significant difference among three groups at baseline. |
| Time to the First Spontaneous Bowel Movement After the First Treatment | counting by hours | — |
| Percentage of the Usage of Emergency Drugs | over 4 weeks of treatment | — |
| Change of Mean Value of Cleveland Clinic Score | over 4 weeks of treatment | Cleveland Clinic Score was assessed by doctors which contains eight items about constipation-related symptoms. Score ranges from '0' to '30'. '0' means none of symptoms and '30' means very severe symptoms. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. |
Countries
China
Participant flow
Recruitment details
Recruitment ot this trial started in April 2008 and finished in Dec. 2010. Patients were recruited from clinics in each center by posters and advertisements in newspapers.
Participants by arm
| Arm | Count |
|---|---|
| Deep Needling Group Acupoints of bilateral Tianshu (ST25), which were located according to WHO Standardized Acupuncture Points Location20, were used.
After sterilizing the skin, needles of the size of 0.35×0.75mm were inserted into ST25 vertically and slowly without manipulation for about 30\
70mm until touching the parietal peritoneum. Paired alligator clips of the EA apparatus were attached transversely to the needle holders of bilateral ST25. EA stimulation lasted for 30 minutes with a dilatational wave of 2/15Hz and current intensity of 0.1\
1mA. Participant's abdominal muscle twitching mildly showed the proper dose.
Patients were treated once a day, five times a week for continuous 4 weeks. | 237 |
| Shallow Needling Group Bilateral ST25, the same acupoints as deep needling group, were used. After skin disinfection, needles of the size of 0.30×25mm penetrated the skin uprightly for about 5\
9mm into the fat layer without manipulation. The usage of EA apparatus and treatment course were the same as deep needling group. | 119 |
| Lactulose Group Lactulose Oral Solution was taken orally at the dose of 20\
30ml once every morning after breakfast for continuous 4 weeks. Patients should take lactulose for another 3 months if no severe adverse effect was showed. | 119 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| at the 4th Week of Follow-up | Lost to Follow-up | 20 | 6 | 1 |
| Over 4 Weeks of Treatment | Changed mind, didn't want to participate | 9 | 7 | 4 |
| Over 4 Weeks of Treatment | Lost to Follow-up | 12 | 10 | 16 |
Baseline characteristics
| Characteristic | Deep Needling Group | Total | Lactulose Group | Shallow Needling Group |
|---|---|---|---|---|
| abdominal distention | 1 units on a scale | 1 units on a scale | 1 units on a scale | 2 units on a scale |
| Age, Categorical <=18 years | 3 Participants | 4 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 35 Participants | 70 Participants | 18 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 199 Participants | 401 Participants | 101 Participants | 101 Participants |
| Age, Continuous | 45.18 years STANDARD_DEVIATION 17.28 | 44.87 years STANDARD_DEVIATION 17.29 | 43.71 years STANDARD_DEVIATION 17.23 | 45.21 years STANDARD_DEVIATION 17.4 |
| Cleveland Clinic Score | 13 units on a scale | 13 units on a scale | 13 units on a scale | 13 units on a scale |
| Incomplete evacuation | 2 units on a scale | 2 units on a scale | 2 units on a scale | 2 units on a scale |
| mean spontaneous bowel movements | 2 stools/week | 2 stools/week | 2 stools/week | 2 stools/week |
| Race/Ethnicity, Customized Han | 229 participants | 458 participants | 114 participants | 115 participants |
| Race/Ethnicity, Customized Minority | 8 participants | 17 participants | 5 participants | 4 participants |
| Region of Enrollment China | 237 participants | 475 participants | 119 participants | 119 participants |
| Sex: Female, Male Female | 183 Participants | 372 Participants | 98 Participants | 91 Participants |
| Sex: Female, Male Male | 54 Participants | 103 Participants | 21 Participants | 28 Participants |
| Stool consistency | 3 units on a scale | 3 units on a scale | 3 units on a scale | 3 units on a scale |
| straining during defecation | 3 units on a scale | 3 units on a scale | 3 units on a scale | 3 units on a scale |
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 | 6 / 228 | 5 / 112 | 10 / 115 |
| serious Total, serious adverse events | 0 / 228 | 0 / 112 | 0 / 115 |
Outcome results
Primary
Change of Mean Weekly Spontaneous Bowel Movements
Spontaneous bowel movements per week were assessed every week during 4 weeks of treatment according to patients' diaries. Weekly spontaneous bowel movements were also assessed at the 4th and 12th week of follow-up according to patients' diaries.
Time frame: over 4-week treatment, at the 4th week of follow-up, at the 12th week of follow-up
Population: Intention-To-Treat(ITT) analysis was used.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Deep Needling Group | Change of Mean Weekly Spontaneous Bowel Movements | over 4 weeks of treatment | 2 stools/week |
| Deep Needling Group | Change of Mean Weekly Spontaneous Bowel Movements | at the 12th week of follow-up | 2 stools/week |
| Deep Needling Group | Change of Mean Weekly Spontaneous Bowel Movements | at the 4th week of follow-up | 2 stools/week |
| Shallow Needling Group | Change of Mean Weekly Spontaneous Bowel Movements | over 4 weeks of treatment | 2 stools/week |
| Shallow Needling Group | Change of Mean Weekly Spontaneous Bowel Movements | at the 4th week of follow-up | 2 stools/week |
| Shallow Needling Group | Change of Mean Weekly Spontaneous Bowel Movements | at the 12th week of follow-up | 1.5 stools/week |
| Lactulose Group | Change of Mean Weekly Spontaneous Bowel Movements | over 4 weeks of treatment | 2 stools/week |
| Lactulose Group | Change of Mean Weekly Spontaneous Bowel Movements | at the 12th week of follow-up | 1 stools/week |
| Lactulose Group | Change of Mean Weekly Spontaneous Bowel Movements | at the 4th week of follow-up | 1 stools/week |
Comparison: at the 4th week of follow-upp-value: 0.001Least-Significant Difference
Comparison: Comparison among three groups over 4 weeks of treatmentp-value: 0.238Kruskal-Wallis
Comparison: Comparison among three groups at the 4th week of follow-upp-value: 0.004Kruskal-Wallis
Comparison: at the 4th week of follow-upp-value: 0.277Least-Significant Difference
Comparison: at the 4th week of follow-upp-value: 0.055Least-Significant Difference
Comparison: Comparison among three groups at the 12th week of follow-upp-value: 0.001Kruskal-Wallis
Comparison: at the 12th week of follow-upp-value: 0.33Least-Significant Difference
Comparison: at the 12th week of follow-upp-value: <0.001Least-Significant Difference
Comparison: at the 12th week of follow-upp-value: 0.018Least-Significant Difference
Secondary
Change of Mean Value of Abdominal Distention
Score of abdominal distention was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of abdominal distention over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. We corrected the mean value of abdominal distention by covariance because the data had significant difference among three groups at baseline.
Time frame: over 4 weeks of treatment
Population: ITT analysis was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Needling Group | Change of Mean Value of Abdominal Distention | 0.762 units on a scale | Standard Deviation 0.033 |
| Shallow Needling Group | Change of Mean Value of Abdominal Distention | 0.693 units on a scale | Standard Deviation 0.041 |
| Lactulose Group | Change of Mean Value of Abdominal Distention | 0.661 units on a scale | Standard Deviation 0.047 |
p-value: 0.167ANOVA
Secondary
Change of Mean Value of Cleveland Clinic Score
Cleveland Clinic Score was assessed by doctors which contains eight items about constipation-related symptoms. Score ranges from '0' to '30'. '0' means none of symptoms and '30' means very severe symptoms. The change was calculated as the value at baseline minus the average over 4 weeks of treatment.
Time frame: over 4 weeks of treatment
Population: ITT analysis was used
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deep Needling Group | Change of Mean Value of Cleveland Clinic Score | 4.5 units on a scale |
| Shallow Needling Group | Change of Mean Value of Cleveland Clinic Score | 4.38 units on a scale |
| Lactulose Group | Change of Mean Value of Cleveland Clinic Score | 4 units on a scale |
p-value: 0.066Kruskal-Wallis
Secondary
Change of Mean Value of Incomplete Evacuation
Score of incomplete evacuation was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of incomplete evacuation over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment.
Time frame: over 4 weeks of treatment
Population: ITT analysis was used.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deep Needling Group | Change of Mean Value of Incomplete Evacuation | 0.75 units on a scale |
| Shallow Needling Group | Change of Mean Value of Incomplete Evacuation | 0.75 units on a scale |
| Lactulose Group | Change of Mean Value of Incomplete Evacuation | 0.75 units on a scale |
p-value: 0.271Kruskal-Wallis
Secondary
Change of Mean Value of Stool Consistency
Score of stool consistency was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of stool consistency over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. We corrected the mean value of stool consistency by covariance because the data had significant difference among three groups at baseline.
Time frame: over 4 weeks of treatment
Population: ITT analysis was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Needling Group | Change of Mean Value of Stool Consistency | 0.414 units on a scale | Standard Deviation 0.025 |
| Shallow Needling Group | Change of Mean Value of Stool Consistency | 0.438 units on a scale | Standard Deviation 0.035 |
| Lactulose Group | Change of Mean Value of Stool Consistency | 0.701 units on a scale | Standard Deviation 0.035 |
p-value: <0.001ANOVA
p-value: 0.58Least-Significant Difference
p-value: <0.001Least-Significant Difference
p-value: <0.001Least-Significant Difference
Secondary
Change of Mean Value of Straining During Defecating
Score of straining during defecating was assessed every week according to patients' diaries during 4 weeks of treatment. Score ranges from '0' to '4'. '0' means none of symptoms and '4' means very severe symptoms. Change from baseline of the mean value of straining during defecating over 4 weeks of treatment was evaluated as the secondary outcome. The change was calculated as the value at baseline minus the average over 4 weeks of treatment. We corrected the mean value of straining during defecating by covariance because the data had significant difference among three groups at baseline.
Time frame: over 4 weeks of treatment
Population: ITT analysis was used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Needling Group | Change of Mean Value of Straining During Defecating | 0.835 units on a scale | Standard Deviation 0.037 |
| Shallow Needling Group | Change of Mean Value of Straining During Defecating | 0.789 units on a scale | Standard Deviation 0.053 |
| Lactulose Group | Change of Mean Value of Straining During Defecating | 0.868 units on a scale | Standard Deviation 0.053 |
p-value: 0.573ANOVA
Secondary
Percentage of the Usage of Emergency Drugs
Time frame: at the 12th week of follow-up
Population: ITT analysis was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deep Needling Group | Percentage of the Usage of Emergency Drugs | 17.11 percentage of participants |
| Shallow Needling Group | Percentage of the Usage of Emergency Drugs | 14.29 percentage of participants |
| Lactulose Group | Percentage of the Usage of Emergency Drugs | 29.57 percentage of participants |
p-value: 0.006Chi-squared
p-value: 0.507Chi-squared
p-value: 0.005Chi-squared
p-value: 0.008Chi-squared
Secondary
Percentage of the Usage of Emergency Drugs
Time frame: over 4 weeks of treatment
Population: ITT analysis was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deep Needling Group | Percentage of the Usage of Emergency Drugs | 9.65 percentage of participants |
| Shallow Needling Group | Percentage of the Usage of Emergency Drugs | 8.04 percentage of participants |
| Lactulose Group | Percentage of the Usage of Emergency Drugs | 33.91 percentage of participants |
p-value: <0.001Chi-squared
p-value: 0.627Chi-squared
p-value: <0.001Chi-squared
p-value: <0.001Chi-squared
Secondary
Percentage of the Usage of Emergency Drugs
Time frame: at the 4th week of follow-up
Population: ITT analysis was used
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deep Needling Group | Percentage of the Usage of Emergency Drugs | 10.53 percentage of participants |
| Shallow Needling Group | Percentage of the Usage of Emergency Drugs | 12.50 percentage of participants |
| Lactulose Group | Percentage of the Usage of Emergency Drugs | 30.43 percentage of participants |
p-value: <0.001Chi-squared
p-value: 0.587Chi-squared
p-value: 0.001Chi-squared
p-value: <0.001Chi-squared
Secondary
Time to the First Spontaneous Bowel Movement After the First Treatment
Time frame: counting by hours
Population: ITT analysis was used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Needling Group | Time to the First Spontaneous Bowel Movement After the First Treatment | 27.08 hours | Standard Deviation 27.53 |
| Shallow Needling Group | Time to the First Spontaneous Bowel Movement After the First Treatment | 36.68 hours | Standard Deviation 32.75 |
| Lactulose Group | Time to the First Spontaneous Bowel Movement After the First Treatment | 16.52 hours | Standard Deviation 18.84 |
p-value: <0.001ANOVA
p-value: 0.024Least-Significant Difference
p-value: <0.001Least-Significant Difference
p-value: <0.001Least-Significant Difference