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

Study Overview
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Brief Summary
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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.

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

Conditions
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Inflammatory Bowel Disease (IBD)

Intervention / Treatment
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* Biological: Standard dose Influenza vaccine (SDIV)
* Biological: High dose influenza vaccine (HDIV)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control Group<br>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)<br> <br> |
| Other: Vedolizumab Group + standard dose influenza vaccine (SDIV)<br>A group of 20 patients who are currently on vedolizumab. All individuals in this group will receive SDIV | Biological: Standard dose Influenza vaccine (SDIV)<br> <br> |
| Other: High dose influenza vaccine (HDIV)<br>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)<br> <br> |
| Other: Standard dose influenza vaccine (SDIV)<br>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)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Antibody Concentrations in Immunosuppressed IBD Patients Who Receive High Dose and Standard of Care Dose Influenza Vaccine | 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. | Pre-immunization and 2-4 weeks post immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate Against Influenza Vaccine in Patients With Inflammatory Bowel Disease: Number of Participants Positive for Seroconversion | 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. | 4 weeks | 
| Seroprotection: Number of Participants With Antibody Concentration at Least 1:40 at Week 4 Postimmunization | 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 | 4 weeks | 
| Seroprotection: Number of Participants With Antibody Titer of 160 at Week 4 Post-immunization | Seroprotection is defined by the FDA as post-immunization concentration of 1:160 that confers protection from infection to 95% of the population. | 4 weeks | 
| Measure Antibody Concentrations in Immunosuppressed IBD Patients Who Receive High Dose and Standard of Care Dose Influenza Vaccine | 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. | 6 months post-immunization |