Effect of Acupuncture on the Microbiota-gut-brain Axis in Crohn's Disease

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.

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Other: Acupuncture treatment; Other: Sham acupuncture

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acupuncture group; Subjects in this group will receive real acupuncture combined with real moxibustion.	Other: Acupuncture 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.
Sham Comparator: Sham group; Subjects in this group will receive sham acupuncture combined with sham moxibustion.	Other: Sham 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Acupuncture on Crohn's Disease Activity Index (CDAI)	Difference in Crohn's Disease Activity Index (CDAI) from baseline at 12 weeks was used for between-group assessment.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Acupuncture on Anxiety and Depression	Differences in Hospital Anxiety Depression Scale (HADS) scores from baseline at 12 weeks were used for between-group assessment.	Week 12
Effects of Acupuncture on Quality of Life	Differences in Inflammatory Bowel Disease Questionnaire (IBDQ) scores from baseline at 12 weeks were used for between-group assessment.	Week 12
Effect of acupuncture on intestinal inflammation	Differences in serum C-reactive protein levels and faecal calprotectin levels from baseline at 12 weeks were used for between-group assessment.	Week 12
Effects of acupuncture on gut microbiota	This includes the alpha and beta diversity of gut microbes and the abundance of flora at each level.	Week 12
Effects of acupuncture on the functional activity of brain networks	Including brain network graph theory properties, connection strength.	Week 12
Effects of acupuncture on intestinal inflammation	Including intestinal barrier function, peripheral Th1/Th17-related inflammatory factors.	Week 12
Effect of Acupuncture on Brain Imaging-Gut Microbiological Correlations	The effect of acupuncture was observed by constructing correlations between brain imaging parameters and gut microbiology and gut inflammation levels.	Week 12
Safety evaluation (number of participants with abnormal reactions to acupuncture and moxibustion treatment)	Abnormal reactions after acupuncture and moxibustion, such as bleeding, hematoma, scald, dizziness and other phenomena.	Week 12
Safety evaluation (number of participants with abnormal routine blood tests)	Routine blood tests, which mainly include the number of red blood cells, white blood cells and platelets per litre of blood.	Week 12
Safety evaluation (number of participants with abnormal Liver function tests)	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).	Week 12
Safety evaluation (number of participants with abnormal Renal function tests)	Renal function tests, mainly including tests of creatinine (μmol/L) and urea nitrogen (mmol/L) concentrations in peripheral blood.	Week 12

Collaborators and Investigators

• Sponsor: Shanghai Institute of Acupuncture, Moxibustion and Meridian
• Collaborators: Fudan University
• Investigators: Study Chair: Huangan Wu, PhD, MD, Shanghai Institute of Acupuncture, Moxibustion and Meridian

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): March 28, 2024

Study Registration Dates

• First Submitted: March 29, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: acupuncture; brain-gut interaction
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: ZYS2024-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No