Inflammatory Bowel Disease
Conditions
Keywords
inflammatory bowel disease (IBD), immunogenicity, safety, HPV, Gardasil, vaccine
Brief summary
Many IBD patients take immunosuppressive agents and we are uncertain as to their capacity to mount a truly protective response after vaccination. If IBD patients do not have an adequate immunological response, they may need to increase the dosage or get booster shots. Many clinicians who treat patients with autoimmune diseases are asking if the vaccine is safe and effective. Thus, this study has important clinical and public health significance because more than one million people in the United States have been diagnosed with IBD. There is not much studied about HPV and immunocompromised patients. Research on healthy women who were immunized with a set of three HPV vaccines demonstrated significantly increased antibody titers. In addition, they had significantly reduced HPV incident and persistent infection and HPV-related disease (cervical, vulvar, and vaginal cancers, cervical intraepithelial neoplasia, genital warts) through five years of follow-up compared to controls who received a placebo. The HPV vaccine was well tolerated without significant side effects. The aims of this research are to measure the immune response in 9-26 year old IBD patients who are on immunosuppressive agents after receiving the HPV vaccine compared with historical controls. We will also evaluate the number and type of vaccine-associated adverse events as well as the disease activity and flare-ups that occur after each dose of vaccine. We hypothesize that IBD patients on immunosuppressive therapy will have have a similar immune response to HPV types 6, 11, 16 and 18 at one month postdose 3 compared to healthy age-matched historical controls. The patient population includes IBD patients who are on immunosuppressive medications. Recruiting approximately 100 patients will provide adequate power for the study. A blood sample will be taken from all IBD patients to evaluate baseline antibody levels and markers (e.g., ESR, CBC, albumin) before or immediately after immunization with the HPV vaccine. Lab tests will be redrawn at 7 months to evaluate the level of antibody titers and follow the markers. During the study, we will track basic laboratory measures, disease status by using the Pediatric Crohn's Disease Active Index or Harvey-Bradshaw Index for UC, side effects from the vaccinations, and other adverse events.
Interventions
BIOLOGICALGardasil vaccine
standard 0.5 mL dose of Gardasil vaccine given at Day 0, Month 2, and Month 6
Sponsors
Harvard School of Public Health (HSPH)
Merck Sharp & Dohme LLC
Boston Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 26 Years
Healthy volunteers
No
Inclusion criteria
1. Crohn's disease, ulcerative colitis, or indeterminate colitis diagnosed by standard clinical, radiographic, endoscopic, and histologic criteria. 2. Actively followed by a physician at the Children's' Hospital gastroenterology (GI) or IBD Center, or patient is referred by local clinic or hospital for our study. 3. Female gender 4. Age 9-26 years 5. Patient (18 years old) or parent is willing to provide informed consent. 6. Is currently on an immunomodulator and/or TNF inhibitor for ≥ 30 days prior to enrollment. Patients may also be using prednisone or aminosalicylates in addition to the immunomodulator or TNF inhibitor. Standard concomitant medications (e.g. antibiotics, antihistamines, acetaminophen) will be allowed
Exclusion criteria
1. Male gender 2. Unwilling to provide consent 3. New immunomodulator added within the last 30 days, and was not previously on any immunomodulator 4. History of bleeding disorder that would make hematoma likely (e.g., hemophilia, von Willebrand's disease) or on anti-coagulation therapy (certain cases may be allowed; each case will be assessed by study doctor) 5. Hypersensitivity to the ingredients/components of the vaccine (e.g., aluminum, yeast) 6. Known pregnancy or positive pregnancy test. We will obtain a urinary pregnancy test before each dose of the vaccine is administered. Subjects participating will be informed during the consent/assent procedures that the safety of this vaccine has not been proven in pregnant women, and will be advised not to become pregnant during the study and counseled according to the guidelines of the Children's Hospital IRB. 7. Previously received HPV vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Titer to HPV 6 | Month 7 | — |
| Antibody Titer to HPV 11 | Month 7 | — |
| Antibody Titers to HPV 16 | Month 7 | Geometric mean titer (95% CI) |
| Antibody Titer to HPV 18 | Month 7 | Geometric mean titer (95%CI) |
Countries
United States
Participant flow
Recruitment details
Location - Children's Hospital Boston, including Waltham Infusion Center, and Maine Medical Center. Patients were recruited during a scheduled clinical or Remicade infusion visit, a hospital admission, by contact through mail followed by a phone call, or through referral from local hospitals. Recruitment period -April 2008 through April 2010
Participants by arm
| Arm | Count |
|---|---|
| Prospective Cohort Received Gardasil as part of study | 37 |
| Retrospective Cohort Patients received Gardasil vaccine from their primary medical provider. They had blood drawn for the study after they completed the vaccine | 15 |
| Total | 52 |
Baseline characteristics
| Characteristic | Retrospective Cohort | Prospective Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 33 Participants | 39 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 4 Participants | 13 Participants |
| Age Continuous | 18.9 years STANDARD_DEVIATION 3.5 | 14.9 years STANDARD_DEVIATION 3.1 | 16.1 years STANDARD_DEVIATION 3.6 |
| Region of Enrollment United States | 15 participants | 37 participants | 52 participants |
| Sex: Female, Male Female | 15 Participants | 37 Participants | 52 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 37 | 0 / 0 |
| serious Total, serious adverse events | 5 / 37 | 0 / 0 |
Outcome results
Primary
Antibody Titers to HPV 16
Geometric mean titer (95% CI)
Time frame: Month 7
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Prospective Cohort | Antibody Titers to HPV 16 | 3975.1 milli-Merck units/mL |
| Retrospective Cohort | Antibody Titers to HPV 16 | 802.7 milli-Merck units/mL |
Primary
Antibody Titer to HPV 11
Time frame: Month 7
Population: Number of participants who completed all vaccine doses
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Prospective Cohort | Antibody Titer to HPV 11 | 1681.8 milli-Merck units/mL |
| Retrospective Cohort | Antibody Titer to HPV 11 | 267.3 milli-Merck units/mL |
Primary
Antibody Titer to HPV 18
Geometric mean titer (95%CI)
Time frame: Month 7
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Prospective Cohort | Antibody Titer to HPV 18 | 857.6 milli-Merck units/mL |
| Retrospective Cohort | Antibody Titer to HPV 18 | 79.5 milli-Merck units/mL |
Primary
Antibody Titer to HPV 6
Time frame: Month 7
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Prospective Cohort | Antibody Titer to HPV 6 | 1079.9 milli-Merck units/mL |
| Retrospective Cohort | Antibody Titer to HPV 6 | 173.4 milli-Merck units/mL |