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

• ClinicalTrials.gov Identifier: NCT05584735
• Recruitment Status: Recruiting
• First Posted: October 18, 2022
• Last Update Posted: November 18, 2023
• Sponsor: University of Wisconsin, Madison
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: October 14, 2022
• First Posted Date: October 18, 2022
• Last Update Posted Date: November 18, 2023
• Actual Study Start Date: November 3, 2023
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2023)

• Influenza or COVID-17 antibody concentrations [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: October 14, 2022)

• Influenza antibody concentrations [ Time Frame: Baseline ]
  Hemagglutination inhibition assay (HIA) will be used to measure influenza antibodies in blood.
• Influenza antibody concentrations [ Time Frame: One blood draw between 14-28 days after baseline ]
  Hemagglutination inhibition assay (HIA) will be used to measure influenza antibodies in blood.
• Microbiome metrics [ Time Frame: One stool collection between days 0-28 ]
  Microbiome metrics will include phylogenetic diversity, and analyses of relative abundance of microbes using 16SrRNA gene sequence data from fecal material.
• Microbiome stability [ Time Frame: One stool collection between days 0-28 ]
  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.

Current Secondary Outcome Measures (submitted: October 2, 2023)

• Correlation between Fecal Metabolomic Activity and Vaccine Response [ Time Frame: up to 65 days ]
• Correlation between Saliva DNA and Vaccine Response [ Time Frame: up to 65 days ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Determining the Relationship Between Gut Microbiota and Immune Response to Influenza or COVID-19 Vaccine
• Official Title: Determining the Relationship Between Gut Microbiota and Immune Response to Influenza or COVID-19 Vaccine in Immunosuppressed Patients With Inflammatory Bowel Disease
• 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 Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood, Saliva, and Fecal samples

• Sampling Method: Non-Probability Sample
• Study Population: Participants diagnosed with IBD
• Condition: Inflammatory Bowel Diseases

Intervention

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

Study Groups/Cohorts

Participants with Inflammatory Bowel Disease (IBD)

Participants with IBD who are receiving a flu or COVID-19 vaccine

Interventions:

• Biological: Influenza vaccine
• Biological: COVID-19 vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 14, 2022): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2024
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marie Najdowski; 608-262-0162; mnajdowski@medicine.wisc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05584735
• Other Study ID Numbers: 2021-0977; A534250 ( Other Identifier: UW Madison ); SMPH/MEDICINE/GASTROENT ( Other Identifier: UW Madison ); Protocol version 7/19/2023 ( Other Identifier: UW Madison )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Wisconsin, Madison
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Wisconsin, Madison
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Wisconsin, Madison
• Verification Date: November 2023