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

Inflammatory Bowel Disease Clinical Trial

— HPV  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00727636
• Other study ID #: 07-09-0344
• Status: Completed
• Phase: N/A
• First received: July 31, 2008
• Last updated: May 3, 2011
• Start date: July 2008
• Est. completion date: April 2011

Study information

• Verified date: May 2011
• Source: Children's Hospital Boston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: April 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 9 Years to 26 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Biological:
• Gardasil vaccine
standard 0.5 mL dose of Gardasil vaccine given at Day 0, Month 2, and Month 6

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital Boston	Harvard School of Public Health, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody Titer to HPV 6		Month 7	No
Primary	Antibody Titer to HPV 11		Month 7	No
Primary	Antibody Titers to HPV 16	Geometric mean titer (95% CI)	Month 7	No
Primary	Antibody Titer to HPV 18	Geometric mean titer (95%CI)	Month 7	No