Immunogenicity to Human Papillomavirus Vaccine (Gardasil) Among IBD Patients on Immunosuppressive Therapy (HPV)

Pilot Study of Immunogenicity and Tolerability to the Quadrivalent Human Papillomavirus Virus-like Particle (VLP) Vaccine (Gardasil) Among IBD Patients on Immunosuppressive Therapy Compared to Healthy Children and Youth Adult Females

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Biological: Gardasil vaccine

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gardasil vaccine - Prospective Study; Prospective study participants received the Gardasil vaccine during the study	Biological: Gardasil vaccine; standard 0.5 mL dose of Gardasil vaccine given at Day 0, Month 2, and Month 6; Other Names: Gardasil, HPV vaccine
No Intervention: Retrospective Study; Retrospective study participants had blood drawn in the study after they had received the Gardasil vaccine from their primary medical provider

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Titer to HPV 6		Month 7
Antibody Titer to HPV 11		Month 7
Antibody Titers to HPV 16	Geometric mean titer (95% CI)	Month 7
Antibody Titer to HPV 18	Geometric mean titer (95%CI)	Month 7

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Merck Sharp & Dohme LLC; Harvard School of Public Health (HSPH)
• Investigators: Principal Investigator: Athos Bousvaros, MD, Boston Children's Hospital; Principal Investigator: Denise L Jacobson, PhD, MPH, Harvard School of Public Health (HSPH)

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: July 31, 2008
• First Submitted That Met QC Criteria: August 1, 2008
• First Posted (Estimate): August 4, 2008

Study Record Updates

• Last Update Posted (Estimate): May 27, 2011
• Last Update Submitted That Met QC Criteria: May 3, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: safety; vaccine; immunogenicity; HPV; Gardasil; inflammatory bowel disease (IBD)
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 07-09-0344