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

Study Overview
=================
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.

Official Title
-----------------
Changes in Intestinal Microecology Before and After Vedolizumab Treatment for Ulcerative Colitis and Correlation With Efficacy

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: Vedolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older, with moderate to severe ulcerative colitis, with an indication for vedolizumab treatment; Consent to participate in the study, read and sign the informed consent form; No previous treatment with vedolizumab; Never undergone biologic therapy or at least suspended previous biologic therapy for more than 12 weeks; Not taking antibiotics or probiotics within the past 4 weeks. Exclusion Criteria: younger than 18 years of age; pregnant or breastfeeding women; patients who require the assistance of a surrogate, witness, or who are otherwise unable to complete the trial unaided; other conditions that, in the opinion of the investigator, are unsuitable for enrollment or affect the subject's ability to complete the study; have taken antibiotics or probiotics within the past 4 weeks; have received prior treatment with vedolizumab.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group of UC patients treated with vedolizumab<br>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 | Drug: Vedolizumab<br>* Recommended dose in patients with UC: 300 mg intravenously at weeks 0, 2, and 6 and every 8 weeks thereafter. Discontinue vedolizumab at week 14 in patients who do not show treatment benefit.<br>|
| No Intervention: Normal control group<br>On the basis of the exclusion criteria, there are no significant intestinal inflammatory, autoimmune or neoplastic disorders. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate of patients | Clinical remission response rates（Mayo score≤2） | 1 year | 

Secondary Outcome Measures

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