Clinical trial NCT01364896: Anal Human Papillomavirus in Inflammatory Bowel Disease Study
Official title: Characterization of Anal Human Papillomavirus (HPV) Infection in the University of Pittsburgh Inflammatory Bowel Disease (IBD) Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Disease (IBD)
Ulcerative Colitis (UC)
Crohn's Disease (CD)
Anal Human Papillomavirus
Keywords: Non-corticosteroid immunosuppressive agent
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-06-03
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men and women 18 years + with a histological diagnosis of IBD (ulcerative colitis or Crohn's disease) who are undergoing a colonoscopy prior to starting a non-corticosteroid immunosuppressive agent

Brief summary: This is an observational cohort study with two time points (baseline and after at least 6 months of treatment with a non-corticosteroid immunosuppressive agent for inflammatory bowel disease (IBD)). Approximately 40 participants, both male and female, 18 years of age and older will be recruited from the Pittsburgh IBD Cohort.

Participants will have a histological diagnosis of IBD (Ulcerative Colitis (UC) or Crohn's Disease (CD)) and will be attending for colonoscopy prior to starting a non-corticosteroid immunosuppressive agent as part of standard medical care. Immediately following the colonoscopy, an anal exam will be performed for research purposes to include:

1. Perianal inspection
2. Anal canal HPV swab
3. Anal cytology
4. Digital anal examination
5. High resolution anoscopy (HRA) and biopsy of all lesions with visual criteria consistent with high-grade anal dysplasia
6. For female participants a self- or clinician-taken vaginal swab for HPV typing.

These procedures will be repeated at routine colonoscopy following at least 6 months but within 12 months of non-corticosteroid immunosuppressive treatment.

Detailed description: Treatment of IBD relies on disease modification by induction of relative immunosuppression with corticosteroids and latterly and increasingly, by the use of immunomodulators (azathioprine, mercaptopurine, methotrexate), biological agents such as anti tumor necrosis factor monoclonal antibodies (infliximab, adalimumab, certolizumab) or with a circulating receptor fusion protein (etanercept). These agents impair cell mediated immunity (CMI) and have been associated with increased rates of both tuberculosis and fungal infections in treated populations beyond that seen with corticosteroids alone. Following initial infection, HPV is controlled by CMI and manifestations of infection become increasingly clinically apparent when CMI is impaired due to for example HIV co-infection or systemic immunosuppression. There is appropriate concern in the IBD treatment community that the use of immunosuppression to modify disease course may lead to increased rates of HPV associated disease including warts, dysplasia and ultimately anogenital cancer above and beyond the established increased risk associated with IBD. In this context it is important to establish the prevalence of both HPV infection and anal dysplasia in patients with IBD before and after treatment with a non-steroid immunosuppressive agent. These data will help determine the need for HPV vaccination and/or anal dysplasia screening in patients with IBD.

VISIT 1 (Screening/Enrollment Visit): This visit will include:

* Medical/medication history.
* Physical exam as per standard of care
* Females of reproductive potential will give a urine sample for a pregnancy test. This test must be negative.
* An anal Pap test for abnormal cells. The researcher will insert a swab (similar to a Q-tip) into the anus. The end of the swab will be rubbed against the skin inside the anus.
* An anal swab to test for HPV (using the same method as the anal Pap)
* Female participants will also have a vaginal swab for HPV. This may be self taken, or taken by a clinician.
* An exam of the anus and genital area for any lesions or masses.
* A rectal exam with a finger to feel for any abnormalities.
* An anal exam called high resolution anoscopy (HRA) that uses a special microscope and dyes to examine the anus for abnormal areas. A lubricated plastic speculum will be inserted into the anus. Then, a swab moistened with acetic acid is placed in the anus so that abnormal areas will be visible. A colposcope will be used to view the skin inside the anus. A biopsy, with or without iodine for visualization of the abnormal areas, may be taken if any lesions have the appearance of high-grade anal dysplasia or other abnormal findings.

Within 1 day after this visit, study staff will telephone the participant to ask about any side effects or health problems from the study procedures. If necessary, the participant may be asked to come to the clinic for a visit.

VISIT 2 (Final Visit): This visit will occur 6 to 12 months after the first visit. Prior to this visit, participant will be instructed to not have anal sex or insert anything into the anus, including enemas, for 24 hours before each study visit. This visit will include:

* Medical/medication history
* Physical exam as per standard of care
* Females of reproductive potential will give a urine or 5ml blood sample\] for a pregnancy test. This test must be negative.
* Anal Pap test for abnormal cells
* Anal swab for HPV
* Females participants will also have a vaginal swab for HPV
* An exam of the anus and genital area for any lesions, tenderness or masses
* A rectal exam to feel for any abnormalities
* High-resolution anoscopy (HRA). A biopsy, with or without iodine for visualization of the abnormal areas, may be taken if any lesions have the appearance of high-grade anal dysplasia or other abnormal findings.

Within 1 day after this visit, study staff will telephone the participant to ask about any side effects or health problems from the study procedures. If necessary, the participant may be asked to come to the clinic for a visit.

Eligibility criteria: Inclusion Criteria:

1. Previous biopsy proven inflammatory bowel disease (ulcerative colitis or Crohn's disease)
2. Male or female over 18 years of age
3. Able and willing to give informed consent in English
4. Able and willing to provide locator information
5. Planned commencement of a non-corticosteroid immunosuppressive agent for management of inflammatory bowel disease
6. Sexually active
7. Female subjects of reproductive potential must agree to use an acceptable method of birth control while on this study.

Exclusion Criteria:

1. Previous or current treatment with a biological agent for inflammatory bowel disease
2. Any other condition or prior therapy that, in the opinion of the investigator, would make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease
3. For female subjects of reproductive potential, current pregnancy, pregnancy within the 90 days prior to study entry, or planning to become pregnant within 12 months after study entry
4. For female subjects, currently breastfeeding

Primary outcomes:
measure: Number of Participants With Anal HPV of Any Type, Single Type, and Multiple Types
timeFrame: Baseline and 6 to 12 months
measure: Percent of Participants With HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and/or 58
timeFrame: Baseline and 6 to 12 months
measure: Number of Participants With Abnormal Anal Cytology (ASC-US, ASC-H, LSIL, HSIL, Cancer)
timeFrame: Baseline and 6 to 12 months
measure: Number of Participants Who Had One or More Anal Biopsies
timeFrame: Baseline and 6 to 12 months
measure: Number of Participants With High-grade Anal Dysplasia Lesions
timeFrame: Baseline and 6 to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ross Cranston, M.D.
role: PRINCIPAL_INVESTIGATOR
References: