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

• ClinicalTrials.gov Identifier: NCT02461758
• Recruitment Status: Completed
• First Posted: June 3, 2015
• Results First Posted: September 13, 2019
• Last Update Posted: October 2, 2019
• Sponsor: University of Wisconsin, Madison
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Inflammatory Bowel Disease (IBD)	Biological: Standard dose Influenza vaccine (SDIV); Biological: High dose influenza vaccine (HDIV)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
• Study Start Date: October 2016
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: July 2018

Arms and Interventions

Arm	Intervention/treatment
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.	Biological: Standard dose Influenza vaccine (SDIV)
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	Biological: Standard dose Influenza vaccine (SDIV)
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.	Biological: High dose influenza vaccine (HDIV)
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.	Biological: Standard dose Influenza vaccine (SDIV)

Outcome Measures

Primary Outcome Measures :

1. Measure Antibody Concentrations in Immunosuppressed IBD Patients Who Receive High Dose and Standard of Care Dose Influenza Vaccine [ Time Frame: Pre-immunization and 2-4 weeks post immunization ]

   Influenza vaccine antibody concentration will be measured in immunosuppressed IBD patients who receive high dose and standard of care dose influenza vaccine.

   Higher antibody concentrations are associated with better protection from infection.

Secondary Outcome Measures :

1. Response Rate Against Influenza Vaccine in Patients With Inflammatory Bowel Disease: Number of Participants Positive for Seroconversion [ Time Frame: 4 weeks ]
   Vaccine response rates for influenza vaccines in patients with inflammatory bowel disease will be accessed by number of patients who has shown significant seroconversion. Seroconversion is defined as a four fold increase in antibody concentration from preimmunization to 4 weeks post immunization.
2. Seroprotection: Number of Participants With Antibody Concentration at Least 1:40 at Week 4 Postimmunization [ Time Frame: 4 weeks ]
   Seroprotection is defined as an antibody concentration of at least 1:40 at 4 weeks post-immunization which confers protection from infection in about 50% of individuals
3. Seroprotection: Number of Participants With Antibody Titer of 160 at Week 4 Post-immunization [ Time Frame: 4 weeks ]
   Seroprotection is defined by the FDA as post-immunization concentration of 1:160 that confers protection from infection to 95% of the population.
4. Measure Antibody Concentrations in Immunosuppressed IBD Patients Who Receive High Dose and Standard of Care Dose Influenza Vaccine [ Time Frame: 6 months post-immunization ]

   Influenza vaccine antibody concentration will be measured in immunosuppressed IBD patients who receive high dose and standard of care dose influenza vaccine.

   Higher antibody concentrations are associated with better protection from infection.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Wisconsin

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

University of Wisconsin, Madison

Investigators

• Principal Investigator: Freddy Caldera; University of Wisconsin School of Medicine and Public Health, Madison

  Study Documents (Full-Text)

Documents provided by University of Wisconsin, Madison:

Study Protocol  [PDF] January 27, 2017

Statistical Analysis Plan  [PDF] August 13, 2015

More Information

Publications of Results:

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.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT02461758
• Other Study ID Numbers: 2015-0813; Influenza in IBD ( Other Identifier: Study Team )
• First Posted: June 3, 2015
• Results First Posted: September 13, 2019
• Last Update Posted: October 2, 2019
• Last Verified: September 2019

• 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.: Yes

Additional relevant MeSH terms:

Intestinal Diseases; Inflammatory Bowel Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Vaccines; Immunologic Factors; Physiological Effects of Drugs