Acupuncture Treatment for Active Crohn's Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Acupuncture on Maintaining Active Crohn's Disease Intestinal Homeostasis Via Intestinal Microbiota and Peripheral Immunity: a Randomized Controlled Trial

Conditions
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Crohn's Disease

Intervention / Treatment
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* Device: Acupuncture and moxibustion
* Device: Sham acupuncture and moxibustion


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acupuncture-moxibustion group<br>Receiving acupuncture and moxibustion treatment. | Device: Acupuncture and moxibustion<br>* 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.<br>|
| Sham Comparator: Sham acupuncture-moxibustion group<br>Receiving sham acupuncture and sham moxibustion. | Device: Sham acupuncture and moxibustion<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with clinical remission | Defined as Crohn's disease activity Index (CDAI) < 150 and decrease > 70 | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with clinical remission | Defined as CDAI < 150 and decrease > 70 | Week 24, 36 and 48 | 
| The proportion of patients with clinical response | Defined as CDAI decrease > 70 | Week 12, 24, 36 and 48 | 
| the mean change of CDAI from baseline | Difference in the mean change of CDAI from baseline between groups | Week 12, 24, 36 and 48 | 
| Laboratory tests for disease activity | C-reaction protein, mg/L | Week 12, 24, 36 and 48 | 
| Laboratory tests for disease activity | Erythrocyte sedimentation rate, mm/h | Week 12, 24, 36 and 48 | 
| Laboratory tests for disease activity | blood platelet level, L | Week 12, 24, 36 and 48 | 
| Quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) | QOL assessment for Crohn's disease | Week 12 and 24 | 
| Psychological factors on the Hospital anxiety and depression scale (HADS) | Anxiety and depression assessment for CD | Week 12 and 24 | 
| The mean change of Crohn's disease endoscopic index of severity (CDEIS) | Intestinal inflammation performance | Week 48 | 
| Fecal calprotectin tests for disease activity | Intestinal inflammation assessment | Week 12 | 
| Histological scores for pathogenic manifestations | Hematoxylin-eosin staining and Histological scores | Week 48 | 
| The proportion of clinical recurrences | Defined as CDAI > 150 and increased by ≥70 points or need to adjust drug to control active disease | Week 24，36 and 48 | 
| 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 | Week 12, 24，36 and 48 | 
| 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. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acupuncture, moxibustion, intestinal microbiota, Peripheral immunity, Brain functional and structural changes