Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients

NCT ID: NCT02461758

Last Updated: 2019-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2018-07-31

Brief Summary

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which includes Crohn's disease (CD) and ulcerative colitis (UC). A recent epidemiological investigation estimates that nearly 4 million people worldwide are affected and approximately 1.4 million of these cases occur in the United States. IBD can lead to debilitating symptoms, hospitalizations, decreased quality of life, frequent procedures and/or surgery. Treatment options consist of immunosuppressive therapy, such as systemic corticosteroids, immunomodulators (thiopurines and methotrexate) and/or biologics, such as tumor necrosis factor alpha (TNF) agents or an integrin inhibitor, vedolizumab. They can achieve clinical remission and decrease the risk of complications, but also increase the risk for opportunistic infections, including influenza.

Multiple studies have shown lower influenza vaccine responses in patients with IBD compared to healthy individuals; IBD patients treated with TNF agents or combination therapy (TNF inhibitors and immunomodulators) are very likely to mount a poor immune response. Influenza serum antibody concentration correlates with protection from infection following vaccination. Therefore, increasing influenza antibody responses in patients with IBD would appear to be critical to improving protection from influenza. A high dose (HD) influenza vaccine containing four times more hemagglutinin was licensed based on its ability to induce higher antibody concentrations compared to standard dose (SD) in adults 65 years or older.

Conditions

Inflammatory Bowel Disease (IBD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Control Group

A group of 20 healthy individuals without IBD, other chronic diseases, or immunosuppressive therapy will be enrolled. All healthy individuals will receive standard dose influenza vaccine SDIV.

Group Type: OTHER

Standard dose Influenza vaccine (SDIV)

Intervention Type: BIOLOGICAL

Vedolizumab Group + standard dose influenza vaccine (SDIV)

A group of 20 patients who are currently on vedolizumab. All individuals in this group will receive SDIV

Group Type: OTHER

Standard dose Influenza vaccine (SDIV)

Intervention Type: BIOLOGICAL

High dose influenza vaccine (HDIV)

This arm will be a double blind randomized controlled trial of High dose influenza vaccine (HDIV) for IBD patients on TNF monotherapy.

40 patients will be enrolled and randomized in a 5:3 fashion to HDIV or SDIV. Randomization will generated by a random number generator and investigator will be blinded to randomization scheme.

Group Type: OTHER

High dose influenza vaccine (HDIV)

Intervention Type: BIOLOGICAL

Standard dose influenza vaccine (SDIV)

This arm will be a double blind randomized controlled trial of standard dose influenza vaccine (SDIV) for IBD patients on TNF monotherapy.

40 patients will be enrolled and randomized in a 5:3 fashion to HDIV or SDIV. Randomization will generated by a random number generator and investigator will be blinded to randomization scheme.

Group Type: OTHER

Standard dose Influenza vaccine (SDIV)

Intervention Type: BIOLOGICAL

Interventions

Standard dose Influenza vaccine (SDIV)

Intervention Type: BIOLOGICAL

High dose influenza vaccine (HDIV)

Intervention Type: BIOLOGICAL

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.
• Ages 18-64
• Currently taking anti-TNF therapy (infliximab, golilumab, adalimumab, or certolizumab) for at least 3 months

• 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.
• Ages 18-64
• Currently on vedolizumab therapy

• Age 18-64
• Willing to participate in study

Exclusion Criteria

• Received season's influenza vaccine
• Allergy to eggs or influenza vaccine
• Currently use of systemic steroids in the past 3 months

• Received season's influenza vaccine
• Allergy to eggs or influenza vaccine
• Currently use of systemic steroids in the past 3 months

• Currently on immunosuppressive therapy
• Has a chronic health condition that may have an impact on vaccine antibody concentrations as deemed by the investigators, including chronic liver disease, celiac disease, history of solid organ or bone marrow transplantation.
• Older than age 65 years
• Unconfirmed Measles, Mumps, and Rubella (MMR) vaccination status
• Patients in whom venipuncture are not feasible due to poor tolerability or lack of easy access.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Freddy Caldera

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin School of Medicine and Public Health, Madison

Locations

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States

Countries

United States

References

Caldera F, Hillman L, Saha S, Wald A, Grimes I, Zhang Y, Sharpe AR, Reichelderfer M, Hayney MS. Immunogenicity of High Dose Influenza Vaccine for Patients with Inflammatory Bowel Disease on Anti-TNF Monotherapy: A Randomized Clinical Trial. Inflamm Bowel Dis. 2020 Mar 4;26(4):593-602. doi: 10.1093/ibd/izz164.

Reference Type: RESULT

PMID: 31504526 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Influenza in IBD

Identifier Type: OTHER

Identifier Source: secondary_id

2015-0813

Identifier Type: -

Identifier Source: org_study_id