Back to resultsAcupuncture Treatment for Active Crohn's Disease
Primary Purpose
Crohn's Disease
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Acupuncture and moxibustion
Sham acupuncture and moxibustion
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring acupuncture, moxibustion, intestinal microbiota, Peripheral immunity, Brain functional and structural changes
Eligibility Criteria
Inclusion Criteria:
- meet the diagnostic criteria of Crohn's disease;
- age 16-70 years old;
- patients with mild or moderate disease (150<CDAI<450) and evidence of active inflammation: serum C-reactive protein concentration ≥5 mg/L, fecal calprotectin concentration ≥250 μg/g, or obvious endoscopic evidence of ulcerations during the screening period of past 4 weeks;
- patients who were not responsive, intolerant, dependent, or refused to use any one of the following medications: mesalazine, glucocorticoid, immunomodulator (azathioprine, methotrexate), and anti-TNF-α agents;
- did not take or take one or more of the following drugs: prednisone <15 mg/d for at least one month, azathioprine (<1 mg/kg/d), methotrexate (<15 mg/week), or mesalazine (<4 g/d) for at least 3 months;
- no history of use of anti-TNF-alpha or other biological agents within 3 months immediately preceding the enrolment in the study;
- no previous history of receiving acupuncture;
- provision of written informed consent.
Exclusion Criteria:
- Pregnant or lactating women, and those desirous of conceiving in the near future;
- patients with severe organic diseases;
- patients with mental illness;
- patients receiving antibiotics, probiotics, prebiotics, traditional Chinese medicine, or other drugs;
- patients with multiple comorbid conditions that require long-term therapy with drugs, which may affect the outcome measures;
- patients with severe extraintestinal manifestations, such as severe skin diseases, eye diseases, or thromboembolic diseases;
- severe intestinal fistula, abdominal abscess, intestinal stenosis and intestinal obstruction, perianal abscess, gastrointestinal bleeding, bowel perforation, or other complications;
- patients with short bowel syndrome;
- patients with a history of abdominal or gastrointestinal surgery in the past six months;
- patients with skin diseases or defects at the sites of acupuncture that prevents the application of acupuncture.
Sites / Locations
- Shanghai Institute of Acupuncture, Moxibustion and Meridian
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Acupuncture-moxibustion group
Sham acupuncture-moxibustion group
Arm Description
Receiving acupuncture and moxibustion treatment.
Receiving sham acupuncture and sham moxibustion.
Outcomes
Primary Outcome Measures
The proportion of patients with clinical remission
Defined as Crohn's disease activity Index (CDAI) < 150 and decrease > 70
Secondary Outcome Measures
The proportion of patients with clinical remission
Defined as CDAI < 150 and decrease > 70
The proportion of patients with clinical response
Defined as CDAI decrease > 70
the mean change of CDAI from baseline
Difference in the mean change of CDAI from baseline between groups
Laboratory tests for disease activity
C-reaction protein, mg/L
Laboratory tests for disease activity
Erythrocyte sedimentation rate, mm/h
Laboratory tests for disease activity
blood platelet level, L
Quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ)
QOL assessment for Crohn's disease
Psychological factors on the Hospital anxiety and depression scale (HADS)
Anxiety and depression assessment for CD
The mean change of Crohn's disease endoscopic index of severity (CDEIS)
Intestinal inflammation performance
Fecal calprotectin tests for disease activity
Intestinal inflammation assessment
Histological scores for pathogenic manifestations
Hematoxylin-eosin staining and Histological scores
The proportion of clinical recurrences
Defined as CDAI > 150 and increased by ≥70 points or need to adjust drug to control active disease
Safety evaluation (Number of participants with treatment-related adverse events as assessed by CTCAE v4.0)
Eg. acupuncture related bleeding, hematoma, fainting needle, etc; moxibustion related burns, blistering, etc
Subgroup analysis of the main outcome measure
Compare using chi square test with stratified method or Fisher's exact test, and Gender, BMI, CDAI score at baseline, concomitant medicine, Montreal classification, biologic use history, and surgical history were used as stratification factors.
Full Information
NCT ID
NCT02559037
First Posted
April 16, 2015
Last Updated
April 3, 2020
Sponsor
Shanghai Institute of Acupuncture, Moxibustion and Meridian
Collaborators
Fudan University, Shanghai University of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine, Indiana University School of Medicine, Changhai Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02559037
Brief Title
Acupuncture Treatment for Active Crohn's Disease
Official Title
Effect of Acupuncture on Maintaining Active Crohn's Disease Intestinal Homeostasis Via Intestinal Microbiota and Peripheral Immunity: a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
April 1, 2015 (Actual)
Primary Completion Date
December 31, 2018 (Actual)
Study Completion Date
November 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Institute of Acupuncture, Moxibustion and Meridian
Collaborators
Fudan University, Shanghai University of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine, Indiana University School of Medicine, Changhai Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to observe the efficacy and safety of acupuncture and moxibustion for Crohn's disease and the regulation mechanism of intestinal microbiota and peripheral immunity.
Detailed Description
A randomized controlled trial.
Acupuncture and moxibustion treatment, placebo control.
To observe the efficacy and safety of acupuncture and moxibustion treatment versus placebo controlled for Crohn's disease.
To observe the effect on the regulation of intestinal microbiota in Crohn's disease.
To observe the effect on the regulation of peripheral immunity in Crohn's disease.
To observe the effect on the regulation of brain function and structure in Crohn's disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
acupuncture, moxibustion, intestinal microbiota, Peripheral immunity, Brain functional and structural changes
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acupuncture-moxibustion group
Arm Type
Experimental
Arm Description
Receiving acupuncture and moxibustion treatment.
Arm Title
Sham acupuncture-moxibustion group
Arm Type
Sham Comparator
Arm Description
Receiving sham acupuncture and sham moxibustion.
Intervention Type
Device
Intervention Name(s)
Acupuncture and moxibustion
Intervention Description
Acupuncture acupoints: CV12, bilateral ST36, ST37, SP6, SP9, SP4, LR3 and LI3. Disposable acupuncture auxiliary device and 0.30*40mm or 0.30*25mm acupuncture needles (hwato, suzhou medical supplies factory co., LTD.) were used. The needles were directly inserted 20-30mm into the skin and elicited a de-qi sensation. The needle was kept for 30 min.
Moxibustion acupoints: bilateral ST25 and ST36. Using mild-warm moxibustion, The surface temperature of acupoints were maintained at 43 ℃ ± 1 ℃, 30min for each acupoint. Moxibustion and acupuncture were performed at the same time, once every other day, three times a week, a total of 12 weeks of treatment. After the treatment, subjects were followed up in the weeks 24, 36 and 48.
Intervention Type
Device
Intervention Name(s)
Sham acupuncture and moxibustion
Intervention Description
The acupoints used are same to the experimental group. Same disposable acupuncture auxiliary device and 0.35 * 40mm acupuncture needle (flat and blunt needle tip, Hwato, Suzhou Medical Supplies Factory Co., Ltd.) was selected. When the needle was pricked to the acupoint, it did not penetrating into the skin. The subject only felt slight pain and do not have the de-qi sensation.
Sham moxibustion : by using the same moxa stick, The surface temperature of acupoints were maintained at 37 ℃ ± 1 ℃, 30min for each acupoint. Sham acupuncture and sham moxibustion were performed at the same time. They were treated once every other day, three times a week, a total of 12 weeks. After the treatment, subjects were followed up in the weeks 24, 36 and 48.
Primary Outcome Measure Information:
Title
The proportion of patients with clinical remission
Description
Defined as Crohn's disease activity Index (CDAI) < 150 and decrease > 70
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
The proportion of patients with clinical remission
Description
Defined as CDAI < 150 and decrease > 70
Time Frame
Week 24, 36 and 48
Title
The proportion of patients with clinical response
Description
Defined as CDAI decrease > 70
Time Frame
Week 12, 24, 36 and 48
Title
the mean change of CDAI from baseline
Description
Difference in the mean change of CDAI from baseline between groups
Time Frame
Week 12, 24, 36 and 48
Title
Laboratory tests for disease activity
Description
C-reaction protein, mg/L
Time Frame
Week 12, 24, 36 and 48
Title
Laboratory tests for disease activity
Description
Erythrocyte sedimentation rate, mm/h
Time Frame
Week 12, 24, 36 and 48
Title
Laboratory tests for disease activity
Description
blood platelet level, L
Time Frame
Week 12, 24, 36 and 48
Title
Quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ)
Description
QOL assessment for Crohn's disease
Time Frame
Week 12 and 24
Title
Psychological factors on the Hospital anxiety and depression scale (HADS)
Description
Anxiety and depression assessment for CD
Time Frame
Week 12 and 24
Title
The mean change of Crohn's disease endoscopic index of severity (CDEIS)
Description
Intestinal inflammation performance
Time Frame
Week 48
Title
Fecal calprotectin tests for disease activity
Description
Intestinal inflammation assessment
Time Frame
Week 12
Title
Histological scores for pathogenic manifestations
Description
Hematoxylin-eosin staining and Histological scores
Time Frame
Week 48
Title
The proportion of clinical recurrences
Description
Defined as CDAI > 150 and increased by ≥70 points or need to adjust drug to control active disease
Time Frame
Week 24，36 and 48
Title
Safety evaluation (Number of participants with treatment-related adverse events as assessed by CTCAE v4.0)
Description
Eg. acupuncture related bleeding, hematoma, fainting needle, etc; moxibustion related burns, blistering, etc
Time Frame
Week 12, 24，36 and 48
Title
Subgroup analysis of the main outcome measure
Description
Compare using chi square test with stratified method or Fisher's exact test, and Gender, BMI, CDAI score at baseline, concomitant medicine, Montreal classification, biologic use history, and surgical history were used as stratification factors.
Time Frame
Week 12
Other Pre-specified Outcome Measures:
Title
Intestinal microbiota
Description
Fecal microbiota structure and diversity
Time Frame
Week 12
Title
Plasma inflammatory cytokine levels
Description
IFN-γ, TNF-a, IL-1β IL-17,IL-23 etc.
Time Frame
Week 12
Title
Intestinal barrier function
Description
Plasma Diamine oxidase，lipopolysaccharide, D-lactate level
Time Frame
Week 12
Title
Brain functional changes
Description
Using fMRI (resting-state fMRI)
Time Frame
Week 12
Title
Brain structural changes
Description
brain gray matter, white matter changes
Time Frame
Week 12
Title
Correlation analysis of the change of CRP level and intestinal flora and plasma inflammatory levels at the end of acupuncture treatment
Description
To explore the relationship between CRP and intestinal flora and inflammation influenced by acupuncture
Time Frame
Week 12
Title
Correlation analysis of the change of CRP level and and brain structure and function
Description
To explore the relationship between intestinal inflammation and brain function influenced by acupuncture
Time Frame
Week 12
Title
Correlation analysis of intestinal flora and brain structure and function
Description
To explore the relationship between intestinal flora and brain-gut axis
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
meet the diagnostic criteria of Crohn's disease;
age 16-70 years old;
patients with mild or moderate disease (150<CDAI<450) and evidence of active inflammation: serum C-reactive protein concentration ≥5 mg/L, fecal calprotectin concentration ≥250 μg/g, or obvious endoscopic evidence of ulcerations during the screening period of past 4 weeks;
patients who were not responsive, intolerant, dependent, or refused to use any one of the following medications: mesalazine, glucocorticoid, immunomodulator (azathioprine, methotrexate), and anti-TNF-α agents;
did not take or take one or more of the following drugs: prednisone <15 mg/d for at least one month, azathioprine (<1 mg/kg/d), methotrexate (<15 mg/week), or mesalazine (<4 g/d) for at least 3 months;
no history of use of anti-TNF-alpha or other biological agents within 3 months immediately preceding the enrolment in the study;
no previous history of receiving acupuncture;
provision of written informed consent.
Exclusion Criteria:
Pregnant or lactating women, and those desirous of conceiving in the near future;
patients with severe organic diseases;
patients with mental illness;
patients receiving antibiotics, probiotics, prebiotics, traditional Chinese medicine, or other drugs;
patients with multiple comorbid conditions that require long-term therapy with drugs, which may affect the outcome measures;
patients with severe extraintestinal manifestations, such as severe skin diseases, eye diseases, or thromboembolic diseases;
severe intestinal fistula, abdominal abscess, intestinal stenosis and intestinal obstruction, perianal abscess, gastrointestinal bleeding, bowel perforation, or other complications;
patients with short bowel syndrome;
patients with a history of abdominal or gastrointestinal surgery in the past six months;
patients with skin diseases or defects at the sites of acupuncture that prevents the application of acupuncture.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huangan Wu, MD,PhD
Organizational Affiliation
Shanghai University of TCM
Official's Role
Study Chair
Facility Information:
Facility Name
Shanghai Institute of Acupuncture, Moxibustion and Meridian
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
35198926
Citation
Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, Li G, Zhang J, Zeng X, Chen J, Liu H, Wu H. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial. EClinicalMedicine. 2022 Feb 12;45:101300. doi: 10.1016/j.eclinm.2022.101300. eCollection 2022 Mar.
Results Reference
derived
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Acupuncture Treatment for Active Crohn's Disease
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