A Clinical Standardization Study of the Preferred Acupuncture Treatment Protocol to Treat Functional Constipation

• Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00508482
• Collaborator: Ministry of Science and Technology of the People´s Republic of China (Other)
• Enrollment: 475
• Location: 1
• Arms: 3
• Duration (Months): 43
• Patients Per Site Per Month: 11

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Constipation	Other: deep needling; Drug: Lactulose; Other: shallow needling	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 475 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Clinical Standardization Study of the Preferred Acupuncture Treatment Protocol to Treat Functional Constipation
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: deep needling group Acupoints of bilateral Tianshu (ST25), which were located according to WHO Standardized Acupuncture Points Location, 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 20~60mm until piercing into the muscle layer. Paired alligator clips of the electric acupuncture (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.	Other: deep 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.; Other Names: acupuncture electroacupuncture
Active Comparator: 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.	Drug: Lactulose; 20-30ml, once a day before breakfast, for the whole study except the run-in period; Other Names: Lactulose produced by Solvay Pharmaceuticals BV
Active Comparator: 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.	Other: shallow needling; Huatuo brand needle (0.30×25mm). The usage of EA apparatus and treatment course were the same as deep needling group.; Other Names: acupuncture electroacupuncture

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Time to the First Spontaneous Bowel Movement After the First Treatment [counting by hours]

7. Percentage of the Usage of Emergency Drugs [over 4 weeks of treatment]

8. Percentage of the Usage of Emergency Drugs [at the 4th week of follow-up]

9. Percentage of the Usage of Emergency Drugs [at the 12th week of follow-up]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guang'an Men Hospital Affiliated to China Academy of Chinese Medical Sciences	Beijing	Beijing	China	100053

Sponsors and Collaborators

• Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Ministry of Science and Technology of the People´s Republic of China

Investigators

• Study Director: Zhishun Liu, M.D., Guang'an Men Hospital Affiliated to China Academy of Chinese Medical Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Liu Zhishun, Chief of the Acupuncture Department, Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• ClinicalTrials.gov Identifier: NCT00508482
• Other Study ID Numbers: 2006BAI12B05-1
• First Posted: Jul 30, 2007
• Last Update Posted: Jun 4, 2014
• Last Verified: May 1, 2014

• Keywords provided by Liu Zhishun, Chief of the Acupuncture Department, Guang'anmen Hospital of China Academy of Chinese Medical Sciences: Acupuncture; Functional constipation
• Additional relevant MeSH terms: Constipation; Lactulose

Study Results

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.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Period Title: Over 4 Weeks of Treatment
STARTED	237	119	119
COMPLETED	216	102	99
NOT COMPLETED	21	17	20
Period Title: Over 4 Weeks of Treatment
STARTED	216	102	99
COMPLETED	196	96	98
NOT COMPLETED	20	6	1
Period Title: Over 4 Weeks of Treatment
STARTED	196	96	98
COMPLETED	196	96	98
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	237	119	119	475
Age (Count of Participants)
<=18 years	3 1.3%	1 0.8%	0 0%	4 0.8%
Between 18 and 65 years	199 84%	101 84.9%	101 84.9%	401 84.4%
>=65 years	35 14.8%	17 14.3%	18 15.1%	70 14.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.18 (17.28)	45.21 (17.40)	43.71 (17.23)	44.87 (17.29)
Sex: Female, Male (Count of Participants)
Female	183 77.2%	91 76.5%	98 82.4%	372 78.3%
Male	54 22.8%	28 23.5%	21 17.6%	103 21.7%
Race/Ethnicity, Customized (participants) [Number]
Han	229 96.6%	115 96.6%	114 95.8%	458 96.4%
Minority	8 3.4%	4 3.4%	5 4.2%	17 3.6%
Region of Enrollment (participants) [Number]
China	237 100%	119 100%	119 100%	475 100%
mean spontaneous bowel movements (stools/week) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [stools/week]	2	2	2	2
straining during defecation (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	3	3	3	3
Incomplete evacuation (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	2	2	2	2
Stool consistency (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	3	3	3	3
abdominal distention (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	1	2	1	1
Cleveland Clinic Score (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	13	13	13	13

Outcome Measures

1. Primary Outcome

Title	Change of Mean Weekly Spontaneous Bowel Movements
Description	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

Outcome Measure Data

Analysis Population Description

Intention-To-Treat(ITT) analysis was used.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
over 4 weeks of treatment	2	2	2
at the 4th week of follow-up	2	2	1
at the 12th week of follow-up	2	1.5	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments	Comparison among three groups over 4 weeks of treatment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.238
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments	Comparison among three groups at the 4th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments	at the 4th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.277
	Comments
	Method	Least-Significant Difference
	Comments	We translated the data of three groups through rank cases, so that we can use Least-Significant Difference for the comparison of any two groups.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments	at the 4th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Least-Significant Difference
	Comments	We translated the data of three groups through rank cases, so that we can use Least-Significant Difference for the comparison of any two groups.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments	at the 4th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	Least-Significant Difference
	Comments	We translated the data of three groups through rank cases, so that we can use Least-Significant Difference for the comparison of any two groups.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments	Comparison among three groups at the 12th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments	at the 12th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.330
	Comments
	Method	Least-Significant Difference
	Comments	We translated the data of three groups through rank cases, so that we can use Least-Significant Difference for the comparison of any two groups.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments	at the 12th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Least-Significant Difference
	Comments	We translated the data of three groups through rank cases, so that we can use Least-Significant Difference for the comparison of any two groups.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments	at the 12th week of follow-up
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Least-Significant Difference
	Comments	We translated the data of three groups through rank cases, so that we can use Least-Significant Difference for the comparison of any two groups.

2. Secondary Outcome

Title	Change of Mean Value of Straining During Defecating
Description	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

Outcome Measure Data

Analysis Population Description

ITT analysis was used

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Mean (Standard Deviation) [units on a scale]	0.835 (0.037)	0.789 (0.053)	0.868 (0.053)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.573
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Change of Mean Value of Incomplete Evacuation
Description	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

Outcome Measure Data

Analysis Population Description

ITT analysis was used.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Median (Inter-Quartile Range) [units on a scale]	0.75	0.75	0.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.271
	Comments
	Method	Kruskal-Wallis
	Comments

4. Secondary Outcome

Title	Change of Mean Value of Stool Consistency
Description	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

Outcome Measure Data

Analysis Population Description

ITT analysis was used.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Mean (Standard Deviation) [units on a scale]	0.414 (0.025)	0.438 (0.035)	0.701 (0.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.580
	Comments
	Method	Least-Significant Difference
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Least-Significant Difference
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Least-Significant Difference
	Comments

5. Secondary Outcome

Title	Change of Mean Value of Abdominal Distention
Description	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

Outcome Measure Data

Analysis Population Description

ITT analysis was used.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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. .	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.
Measure Participants	228	112	115
Mean (Standard Deviation) [units on a scale]	0.762 (0.033)	0.693 (0.041)	0.661 (0.047)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.167
	Comments
	Method	ANOVA
	Comments

6. Secondary Outcome

Title	Change of Mean Value of Cleveland Clinic Score
Description	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

Outcome Measure Data

Analysis Population Description

ITT analysis was used

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Median (Inter-Quartile Range) [units on a scale]	4.5	4.38	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments
	Method	Kruskal-Wallis
	Comments

7. Secondary Outcome

Title	Time to the First Spontaneous Bowel Movement After the First Treatment
Time Frame	counting by hours

Outcome Measure Data

Analysis Population Description

ITT analysis was used

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Mean (Standard Deviation) [hours]	27.08 (27.53)	36.68 (32.75)	16.52 (18.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	Least-Significant Difference
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Least-Significant Difference
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Least-Significant Difference
	Comments

8. Secondary Outcome

Title	Percentage of the Usage of Emergency Drugs
Time Frame	over 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

ITT analysis was used.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Number [percentage of participants]	9.65 4.1%	8.04 6.8%	33.91 28.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.627
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Percentage of the Usage of Emergency Drugs
Time Frame	at the 4th week of follow-up

Outcome Measure Data

Analysis Population Description

ITT analysis was used

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Number [percentage of participants]	10.53 4.4%	12.50 10.5%	30.43 25.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.587
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

10. Secondary Outcome

Title	Percentage of the Usage of Emergency Drugs
Time Frame	at the 12th week of follow-up

Outcome Measure Data

Analysis Population Description

ITT analysis was used.

Arm/Group Title	Deep Needling Group	Shallow Needling Group	Lactulose Group
Arm/Group Description	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.	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.	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.
Measure Participants	228	112	115
Number [percentage of participants]	17.11 7.2%	14.29 12%	29.57 24.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Shallow Needling Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deep Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Shallow Needling Group, Lactulose Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	α was corrected by the method of Bonferroni as 0.0167 (α=0.05/3=0.0167).
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	The adverse event data were collected in about more than two years.
Arm/Group Title	Deep Needling Group		Shallow Needling Group		Lactulose Group
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Deep Needling Group		Shallow Needling Group		Lactulose Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Deep Needling Group		Shallow Needling Group		Lactulose Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/228 (0%)		0/112 (0%)		0/115 (0%)
Other (Not Including Serious) Adverse Events
	Deep Needling Group		Shallow Needling Group		Lactulose Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/228 (2.6%)		5/112 (4.5%)		10/115 (8.7%)
Gastrointestinal disorders
diarrhea and abdominal discomfort	0/228 (0%)	0	0/112 (0%)	0	10/115 (8.7%)	10
General disorders
mild fatigue	1/228 (0.4%)	1	1/112 (0.9%)	1	0/115 (0%)	0
Skin and subcutaneous tissue disorders
moderate or above pricking	2/228 (0.9%)	2	1/112 (0.9%)	1	0/115 (0%)	0
Subcutaneous hemorrhage	3/228 (1.3%)	3	3/112 (2.7%)	3	0/115 (0%)	0

Limitations/Caveats

Spontaneous bowel movements were used as the primary outcome in our trial rather than complete, spontaneous bowel movements. Outcomes of follow-up were not the mean value of weekly data.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.