Determining the Relationship Between Gut Microbiota and Immune Response to Influenza or COVID-19 Vaccine

Recruiting

• Conditions: Inflammatory Bowel Diseases
• Interventions: Biological: Influenza vaccine; Biological: COVID-19 vaccine

• Registration Number: NCT05584735
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

This study will evaluate the effect of the microorganisms in the gut on how well the flu or COVID-19 vaccine works in people who have a weakened immune system due to inflammatory bowel disease. Participants can expect to be in the study for up to 65 days.

Detailed Description

The overall objective of this study is to evaluate the role of gut microbiome in influenza or COVID-19 vaccine response in immunosuppressed populations. Microbial diversity (alpha diversity) is decreased in immunosuppressed patients and might be associated with lower immunogenicity to vaccines.

It is known that patients with IBD have dysbiosis of their gut microbiome and those immunosuppressed may have a lower vaccine response. In this aim, the investigators will evaluate whether differences in microbial diversity predict immune response to the influenza and COVID-19 vaccine.

In this prospective study, immunosuppressed IBD patients will be vaccinated per standard of care and blood will be collected to measure the immune response. A fecal and saliva sample will be collected to characterize the gut microbiome. The investigators hypothesize that reduced richness / alpha-diversity in gut microbiota will correlate with those with a blunted vaccine response.

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-14
• Study First Posted: 2022-10-18
• Study Start: 2023-11-03
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-27
• Last Update Posted: 2024-08-28
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• A history of chronic (greater than 3 month) ulcerative colitis or Crohn's disease diagnosed and documented by the standard clinical, radiographic, endoscopic, and histopathologic criteria

• Currently one of the following groups:

  1. Group A: Anti-TNF Therapy Group

     • Maintenance monotherapy: infliximab (at least every 8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly)
     • Combination Therapy: Anti-TNF Combination Therapy Group on anti-TNF therapy as described above along with either methotrexate, azathioprine, or 6MP

  2. Group B: Non-TNG biologic

     • Ustekinumab Therapy: on either ustekinumab monotherapy or combination therapy with methotrexate, azathioprine, or 6MP
     • Vedolizumab Therapy: on either vedolizumab monotherapy or combination therapy with methotrexate, azathioprine, or 6MP
     • Risankizumab Therapy: 360mg at least every 8 weeks

  3. Group C: Janus Kinase Therapy

     • Tofacitinib Therapy: at least 5mg PO BID
     • Upadactinib Therapy: at least 15mg PO daily

• Patient has been on stable treatment for IBD for at least three months

• Must be able to provide research samples between 28-65 days post influenza or Covid-19 vaccination.

Exclusion Criteria

• Member of a vulnerable group (pregnant, lacking consent capacity, non-English speaking)
• Recent oral antibiotics within previous 2 months

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Participants with Inflammatory Bowel Disease (IBD)	Influenza vaccine	Participants with IBD who are receiving a flu or COVID-19 vaccine
Participants with Inflammatory Bowel Disease (IBD)	COVID-19 vaccine	Participants with IBD who are receiving a flu or COVID-19 vaccine

Primary Outcome Measures

Name	Time	Method
Influenza or COVID-17 antibody concentrations	Baseline	Hemagglutination inhibition assay (HIA) will be used to measure influenza antibodies in blood. COVID-19 antibody concentration analysis will be completed with LabCorp's Cov2Quant IgG™ assay which uses immunoassay that uses electrochemiluminescent technology (ECL) for quantitative determination of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2.
Influenza or COVID-19 antibody concentrations	One blood draw between 28-65 days after baseline	Hemagglutination inhibition assay (HIA) will be used to measure influenza antibodies in blood. COVID-19 antibody concentration analysis will be completed with LabCorp's Cov2Quant IgG™ assay which uses immunoassay that uses electrochemiluminescent technology (ECL) for quantitative determination of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2.
Microbiome metrics	One stool collection between days 0-65	Microbiome metrics will include phylogenetic diversity, and analyses of relative abundance of microbes using 16SrRNA gene sequence data from fecal material. Alpha diversity of the microbiome will be evaluated.
Microbiome stability	One stool collection between days 0-65	Microbiome stability will be evaluated using hierarchical clustering of weighted and unweighted UniFrac distances (a beta diversity metric indexing compositional similarity/difference) for microbiome using 16SrRNA gene sequence data from fecal material.

Secondary Outcome Measures

Name	Time	Method
Correlation between Saliva DNA and Vaccine Response	up to 65 days
Correlation between Fecal Metabolomic Activity and Vaccine Response	up to 65 days

Trial Locations

Locations (1)

University of Wisconsin School of Medicine and Public Health; 🇺🇸 Madison, Wisconsin, United States