Crohn's Disease
Conditions
Keywords
acupuncture, moxibustion, intestinal microbiota, Peripheral immunity, Brain functional and structural changes
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
1. A randomized controlled trial. 2. Acupuncture and moxibustion treatment, placebo control. 3. To observe the efficacy and safety of acupuncture and moxibustion treatment versus placebo controlled for Crohn's disease. 4. To observe the effect on the regulation of intestinal microbiota in Crohn's disease. 5. To observe the effect on the regulation of peripheral immunity in Crohn's disease. 6. To observe the effect on the regulation of brain function and structure in Crohn's disease.
Interventions
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.
DEVICESham acupuncture and moxibustion
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.
Sponsors
Fudan University
Shanghai University of Traditional Chinese Medicine
Shanghai Jiao Tong University School of Medicine
Indiana University School of Medicine
Changhai Hospital
Shanghai Institute of Acupuncture, Moxibustion and Meridian
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. meet the diagnostic criteria of Crohn's disease; 2. age 16-70 years old; 3. 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; 4. 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; 5. 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; 6. no history of use of anti-TNF-alpha or other biological agents within 3 months immediately preceding the enrolment in the study; 7. no previous history of receiving acupuncture; 8. provision of written informed consent.
Exclusion criteria
1. Pregnant or lactating women, and those desirous of conceiving in the near future; 2. patients with severe organic diseases; 3. patients with mental illness; 4. patients receiving antibiotics, probiotics, prebiotics, traditional Chinese medicine, or other drugs; 5. patients with multiple comorbid conditions that require long-term therapy with drugs, which may affect the outcome measures; 6. patients with severe extraintestinal manifestations, such as severe skin diseases, eye diseases, or thromboembolic diseases; 7. severe intestinal fistula, abdominal abscess, intestinal stenosis and intestinal obstruction, perianal abscess, gastrointestinal bleeding, bowel perforation, or other complications; 8. patients with short bowel syndrome; 9. patients with a history of abdominal or gastrointestinal surgery in the past six months; 10. patients with skin diseases or defects at the sites of acupuncture that prevents the application of acupuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients with clinical remission | Week 12 | Defined as Crohn's disease activity Index (CDAI) \< 150 and decrease \> 70 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the mean change of CDAI from baseline | Week 12, 24, 36 and 48 | Difference in the mean change of CDAI from baseline between groups |
| Quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) | Week 12 and 24 | QOL assessment for Crohn's disease |
| Psychological factors on the Hospital anxiety and depression scale (HADS) | Week 12 and 24 | Anxiety and depression assessment for CD |
| The mean change of Crohn's disease endoscopic index of severity (CDEIS) | Week 48 | Intestinal inflammation performance |
| Fecal calprotectin tests for disease activity | Week 12 | Intestinal inflammation assessment |
| Histological scores for pathogenic manifestations | Week 48 | Hematoxylin-eosin staining and Histological scores |
| The proportion of clinical recurrences | Week 24，36 and 48 | 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) | Week 12, 24，36 and 48 | Eg. acupuncture related bleeding, hematoma, fainting needle, etc; moxibustion related burns, blistering, etc |
| Subgroup analysis of the main outcome measure | Week 12 | 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. |
| The proportion of patients with clinical remission | Week 24, 36 and 48 | Defined as CDAI \< 150 and decrease \> 70 |
| The proportion of patients with clinical response | Week 12, 24, 36 and 48 | Defined as CDAI decrease \> 70 |
| Laboratory tests for disease activity | Week 12, 24, 36 and 48 | C-reaction protein, mg/L |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma inflammatory cytokine levels | Week 12 | IFN-γ, TNF-a, IL-1β IL-17,IL-23 etc. |
| Intestinal barrier function | Week 12 | Plasma Diamine oxidase，lipopolysaccharide, D-lactate level |
| Brain functional changes | Week 12 | Using fMRI (resting-state fMRI) |
| Brain structural changes | Week 12 | brain gray matter, white matter changes |
| Correlation analysis of the change of CRP level and intestinal flora and plasma inflammatory levels at the end of acupuncture treatment | Week 12 | To explore the relationship between CRP and intestinal flora and inflammation influenced by acupuncture |
| Correlation analysis of intestinal flora and brain structure and function | Week 12 | To explore the relationship between intestinal flora and brain-gut axis |
| Correlation analysis of the change of CRP level and and brain structure and function | Week 12 | To explore the relationship between intestinal inflammation and brain function influenced by acupuncture |
| Intestinal microbiota | Week 12 | Fecal microbiota structure and diversity |
Countries
China
Outcome results
None listed