Crohn Disease
Conditions
Keywords
acupuncture, brain-gut interaction
Brief summary
Multidisciplinary techniques such as multimodal neuroimaging, microbiology, and bioinformatics were applied to study the differences in correlation characteristics between gut microbes, functional brain networks, and peripheral inflammation among patients with active Crohn's disease (CD), CD in remission, and healthy subjects.
Interventions
OTHERAcupuncture treatment
We selected acupoints including Zhongwan (CV12) and bilateral Shangjuxu (ST37), Sanyinjiao (SP6), Gongsun (SP4), Taichong (LR3), Taixi (KI3), Hegu (LI4), and Quchi (LI11)17 according to the World Health Organization standard. Single-use 0.30×40 mm or 0.30×25 mm acupuncture needles (Hwato, Suzhou, China) 27,28 were vertically inserted into each acupoint to 20-30 mm depth to obtain a deqi sensation (a soreness, distention, numbness or heaviness sensation). Bilateral Zusanli (ST36) and Tianshu (ST25) were selected for moxibustion. Pure moxa sticks (diameter: 2.8 cm; Hanyi, Nanyang, China) were ignited and fixed on a moxibustion stand at a distance of 3-5 cm to the surface of acupoints. The temperature of skin surface at the acupoints was maintained at 43 ± 1°C and monitored with a miniature infrared thermometer (Fluke 62, Fluke Corporation, Everett, WA, USA). Acupuncture and moxibustion were concomitantly performed for 30 min.
OTHERSham acupuncture
Sham acupuncture needles (0.35×40 mm) with flat tips (Hwato, Suzhou, China) were inserted towards the same acupoints to induce slight pain but without penetrating the skin. Sham moxibustion was made by igniting the same type of moxa sticks but fixing them at a distance of 8-10 cm from the skin of acupoints to maintain the temperature at 37 ± 1°C. Sham acupuncture and moxibustion were concomitantly performed for 30 min.
Sponsors
Fudan University
Shanghai Institute of Acupuncture, Moxibustion and Meridian
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Subjects, efficacy assessors and statisticians were blinded.
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. 18 ≤ age ≤ 75 years, gender is not limited; 2. Disease in mildly or moderately active stage: 150 ≤ CDAI \< 450 and at least one of the following is met: serum C-reactive protein ≥ 5 mg/L, faecal calreticulin ≥ 250 μg/g, or endoscopic ulceration, or remission stage: CDAI \< 150 and at least one of the following is met: serum C-reactive protein \< 5 mg/L, faecal calreticulin \< 250 μg/g, or endoscopic No ulcers; 3. Not taking or taking the following medications: mesalazine (≤4 g/d and have been taking for ≥1 month), prednisone (≤15 mg/d and have been taking for ≥1 month), and/or azathioprine (≤1 mg/kg/d and have been taking for ≥3 months); 4. Those who have not used biologics within 3 months prior to study entry; 5. Those who have never received acupuncture treatment; 6. Understand, agree to participate in the study and sign an informed consent form.
Exclusion criteria
1. Patients who have recently prepared for pregnancy or are pregnant or breastfeeding; 2. Patients with severe organic pathology; 3. Patients with confirmed psychosis; 4. Patients who are suffering from multiple diseases at the same time and taking other drugs for a long time which may affect the observation of this clinical trial; 5. Patients with severe extra-intestinal manifestations such as severe skin diseases (e.g., erythema nodosum, gangrenous pyoderma, etc.), ocular lesions (e.g., iritis, uveitis, etc.), and thromboembolic diseases; 6. Those with severe intestinal fistulae, abdominal abscesses, intestinal stenosis and intestinal obstruction, perianal lesions (perianal abscesses, etc.), gastrointestinal haemorrhage, intestinal perforation and other complications; 7. Those suffering from short bowel syndrome, those who have undergone abdominal or gastrointestinal surgery within the last six months; 8. Those who are unable to perform acupuncture due to the presence of skin diseases or defects in the area selected for acupuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Acupuncture on Crohn's Disease Activity Index (CDAI) | Week 12 | Difference in Crohn's Disease Activity Index (CDAI) from baseline at 12 weeks was used for between-group assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Acupuncture on Quality of Life | Week 12 | Differences in Inflammatory Bowel Disease Questionnaire (IBDQ) scores from baseline at 12 weeks were used for between-group assessment. |
| Effect of acupuncture on intestinal inflammation | Week 12 | Differences in serum C-reactive protein levels and faecal calprotectin levels from baseline at 12 weeks were used for between-group assessment. |
| Effects of acupuncture on gut microbiota | Week 12 | This includes the alpha and beta diversity of gut microbes and the abundance of flora at each level. |
| Effects of acupuncture on the functional activity of brain networks | Week 12 | Including brain network graph theory properties, connection strength. |
| Effects of acupuncture on intestinal inflammation | Week 12 | Including intestinal barrier function, peripheral Th1/Th17-related inflammatory factors. |
| Effects of Acupuncture on Anxiety and Depression | Week 12 | Differences in Hospital Anxiety Depression Scale (HADS) scores from baseline at 12 weeks were used for between-group assessment. |
| Safety evaluation (number of participants with abnormal reactions to acupuncture and moxibustion treatment) | Week 12 | Abnormal reactions after acupuncture and moxibustion, such as bleeding, hematoma, scald, dizziness and other phenomena. |
| Safety evaluation (number of participants with abnormal routine blood tests) | Week 12 | Routine blood tests, which mainly include the number of red blood cells, white blood cells and platelets per litre of blood. |
| Safety evaluation (number of participants with abnormal Liver function tests) | Week 12 | Liver function tests, mainly including peripheral blood concentrations of alanine aminotransferase (U/L), glutamine aminotransferase (U/L), gamma-glutamyl transpeptidase (U/L), alkaline phosphatase (U/L), total bilirubin (μmol/L), direct bilirubin (μmol/L), indirect bilirubin (μmol/L), total protein (g/L), albumin (g/L) and globulin (g/L). |
| Safety evaluation (number of participants with abnormal Renal function tests) | Week 12 | Renal function tests, mainly including tests of creatinine (μmol/L) and urea nitrogen (mmol/L) concentrations in peripheral blood. |
| Effect of Acupuncture on Brain Imaging-Gut Microbiological Correlations | Week 12 | The effect of acupuncture was observed by constructing correlations between brain imaging parameters and gut microbiology and gut inflammation levels. |
Outcome results
None listed