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

Determining the Relationship Between Gut Microbiota and Immune Response to Influenza or COVID-19 Vaccine in Immunosuppressed Patients With Inflammatory Bowel Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Biological: Influenza vaccine; Biological: COVID-19 vaccine

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 Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Marie Najdowski; Phone Number: 608-262-0162; Email: mnajdowski@medicine.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants diagnosed with IBD

Description

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 8 every 8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly)

  2. Group B: Non-TNG biologic -

     • Ustekinumab on either ustekinumab monotherapy or combination therapy with methotrexate or azathioprine.
     • Vedolizumab Therapy Group: Vedolizumab Therapy: on either vedolizumab monotherapy or combination therapy with methotrexate or azathioprine
     • Risankizumab Therapy: 360mg every 8 weeks

  3. Group C: Janus Kinase Therapy

     • Tofacitinib Therapy Group: on tofacitinib at least 5mg PO BID
     • Upadactinib Therapy Group: on upadactinib at least 15mg PO
• 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 antibiotics within previous 2 months

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with Inflammatory Bowel Disease (IBD); Participants with IBD who are receiving a flu or COVID-19 vaccine	Biological: Influenza vaccine; Observe effects of flu vaccine on microbiome; Biological: COVID-19 vaccine; Observe effects of COVID-19 vaccine on microbiome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Influenza or COVID-17 antibody concentrations	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.	Baseline
Influenza or COVID-19 antibody concentrations	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.	One blood draw between 28-65 days after baseline
Microbiome metrics	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.	One stool collection between days 0-65
Microbiome stability	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.	One stool collection between days 0-65

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between Fecal Metabolomic Activity and Vaccine Response	up to 65 days
Correlation between Saliva DNA and Vaccine Response	up to 65 days

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Freddy Caldera, DO, MS, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Crohn's disease; ulcerative colitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 2021-0977; SMPH/MEDICINE/GASTROENT (Other Identifier: UW Madison); A534250 (Other Identifier: UW Madison); Protocol version 7/19/2023 (Other Identifier: UW Madison)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No