Study of the Effect of Vedolizumab on Intestinal Microecological Changes and Its Efficacy in the Treatment of Ulcerative Colitis

Phase 4

• Conditions: Ulcerative Colitis
• Interventions: Drug: Vedolizumab

• Registration Number: NCT05481619
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

Inflammatory bowel disease is a group of chronic, non-specific inflammatory diseases of the intestinal tract whose etiology has not yet been fully elucidated, including ulcerative colitis and Crohn's disease. Vedolizumab, a novel biologic agent, is a recombinant humanized monoclonal antibody that specifically antagonizes intestine-selective α4β7 integrins on the surface of leukocyte subsets, thereby preventing migration of leukocyte subsets from the blood to the intestinal mucosa and reducing local inflammation in the gut. In this study the investigators propose to build on an existing cohort and analyse, by means of a multi-omics approach, the baseline gut microbial composition and abundance, intestinal and serum metabolome characteristics of UC patients and their changes during treatment, to predict the functional mechanisms by which these changing characteristics influence the therapeutic response to vindolizumab.

Detailed Description

Stool and blood samples etc. were taken from a cohort of patients with ulcerative colitis treated with Vedolizum at the Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine as well as from a cohort of normal volunteers. Stool and blood samples from UC patients were analyzed at baseline and at 14, 30, and 52 weeks after starting treatment. Analysis of changes in gut microbial composition and abundance, gut and serum metabolome characteristics during 52 weeks of treatment in patients with UC. A model for predicting the efficacy of vedolizumab treatment by baseline gut microbial composition and abundance, and gut and serum metabolomic characteristics in patients with ulcerative colitis was developed in conjunction with clinical information from patients in the cohort. Based on the model developed, clinical and gut microbial composition and abundance, gut and serum metabolomics data from other UC patients published in public databases were combined to confirm the results already found using the UC cohort at our center.

Study Timeline

• Study Start: 2021-01-01
• Status Verified: 2022-07
• Study First Submitted: 2022-07-25
• Study First Submitted QC: 2022-07-28
• Last Update Submitted: 2022-07-28
• Study First Posted: 2022-08-01
• Last Update Posted: 2022-08-01
• Primary Completion: 2024-01-01
• Study Completion: 2024-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. 18 years of age or older, with moderate to severe ulcerative colitis, with an indication for vedolizumab treatment;
2. Consent to participate in the study, read and sign the informed consent form;
3. No previous treatment with vedolizumab;
4. Never undergone biologic therapy or at least suspended previous biologic therapy for more than 12 weeks;
5. Not taking antibiotics or probiotics within the past 4 weeks.

Exclusion Criteria

1. younger than 18 years of age;
2. pregnant or breastfeeding women;
3. patients who require the assistance of a surrogate, witness, or who are otherwise unable to complete the trial unaided;
4. other conditions that, in the opinion of the investigator, are unsuitable for enrollment or affect the subject's ability to complete the study;
5. have taken antibiotics or probiotics within the past 4 weeks;
6. have received prior treatment with vedolizumab.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group of UC patients treated with vedolizumab	Vedolizumab	Generic Name：vedolizumab Specification：300mg/bottle Dosage and Method of Administration：Usual adult dose for ulcerative colitis.300 mg IV every 30 minutes at weeks 0, 2, and 6, then every 8 weeks

Primary Outcome Measures

Name	Time	Method
Remission rate of patients	1 year	Clinical remission response rates（Mayo score≤2）

Secondary Outcome Measures

Name	Time	Method
Gut and serum metabolome characteristics of UC patients	1 year	LC-MS mass spectrometry for faecal samples and serum samples to analyze metabolome characteristics
Baseline gut microbial composition and abundance of patients	1 year	Macro-genome sequencing of stool samples to analyze gut microbial composition and abundance

Trial Locations

Locations (1)

Second Affiliated Hospital Zhejiang University School of Medicine; 🇨🇳 Zhengzhou, Hangzhou, China