Clinical trial NCT02461758: Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
Official title: Randomized Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Inflammatory Bowel Disease (IBD)
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2015-06-03
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: CASES Specific Aim #1 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
* Exclusion Criteria
* Received season's influenza vaccine
* Allergy to eggs or influenza vaccine
* Currently use of systemic steroids in the past 3 months

Specific Aim #2 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 on vedolizumab therapy

Exclusion Criteria

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

Control group Inclusion criteria

* Age 18-64
* Willing to participate in study

Control group Exclusion criteria

* 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.

Primary outcomes:
measure: Measure Antibody Concentrations in Immunosuppressed IBD Patients Who Receive High Dose and Standard of Care Dose Influenza Vaccine
timeFrame: Pre-immunization and 2-4 weeks post immunization
Secondary outcomes:
measure: Response Rate Against Influenza Vaccine in Patients With Inflammatory Bowel Disease: Number of Participants Positive for Seroconversion
timeFrame: 4 weeks
measure: Seroprotection: Number of Participants With Antibody Concentration at Least 1:40 at Week 4 Postimmunization
timeFrame: 4 weeks
measure: Seroprotection: Number of Participants With Antibody Titer of 160 at Week 4 Post-immunization
timeFrame: 4 weeks
measure: Measure Antibody Concentrations in Immunosuppressed IBD Patients Who Receive High Dose and Standard of Care Dose Influenza Vaccine
timeFrame: 6 months post-immunization
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin School of Medicine and Public Health, Madison
name: Freddy Caldera
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.