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

Inflammatory Bowel Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05584735
• Other study ID #: 2021-0977
• Secondary ID: A534250SMPH/MEDI
• Status: Recruiting
• Start date: November 3, 2023
• Est. completion date: September 2024

Study information

• Verified date: November 2023
• Source: University of Wisconsin, Madison
• Contact: Marie Najdowski
• Phone: 608-262-0162
• Email: mnajdowski[@]medicine.wisc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Biological:
• Influenza vaccine
Observe effects of flu vaccine on microbiome
• COVID-19 vaccine
Observe effects of COVID-19 vaccine on microbiome

Locations

Country	Name	City	State
United States	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Correlation between Fecal Metabolomic Activity and Vaccine Response		up to 65 days
Secondary	Correlation between Saliva DNA and Vaccine Response		up to 65 days