Anal Human Papillomavirus in Inflammatory Bowel Disease Study (AnalHPV&IBD)

• ClinicalTrials.gov Identifier: NCT01364896
• Recruitment Status: Completed
• First Posted: June 3, 2011
• Results First Posted: March 9, 2016
• Last Update Posted: May 21, 2019
• Sponsor: University of Pittsburgh
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment
Inflammatory Bowel Disease (IBD); Ulcerative Colitis (UC); Crohn's Disease (CD); Anal Human Papillomavirus	Procedure: Venous blood samples, anal swab samples, vaginal swab samples, high resolution anoscopy (HRA), anal biopsy samples

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 46 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Characterization of Anal Human Papillomavirus (HPV) Infection in the University of Pittsburgh Inflammatory Bowel Disease (IBD) Cohort Study
• Study Start Date: June 2011
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: December 2015

Groups and Cohorts

Group/Cohort

Intervention/treatment

Inflammatory bowel disease, Immunosuppressive agent; 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

Procedure: Venous blood samples, anal swab samples, vaginal swab samples, high resolution anoscopy (HRA), anal biopsy samples; Before and at least 6 months after starting a new non-steroid immunosuppressive agent for IBD treatment, eligible participants who are attending for routine colonoscopy will have: Anal swab samples (and vaginal swab samples for female participants) for human papillomavirus PCR typing (6, 11, 16, 18, 31, 33, 45, 52, 58); High-resolution anoscopy and biopsy of all visible high-grade dysplastic lesions based on validated colposcopic criteria; Anal cytology testing

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Anal HPV of Any Type, Single Type, and Multiple Types [ Time Frame: Baseline and 6 to 12 months ]
   Anal (and vaginal for female participants) HPV PCR typing (6, 11, 16, 18, 31, 33, 45, 52, 58) using the SYBR-Green-based real-time PCR assay with a reverse line blot assay for genotyping of HPV in the positive samples and Taqman probe-based real-time PCR assays for quantification of individual HPV subtypes
2. Percent of Participants With HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and/or 58 [ Time Frame: Baseline and 6 to 12 months ]
3. Number of Participants With Abnormal Anal Cytology (ASC-US, ASC-H, LSIL, HSIL, Cancer) [ Time Frame: Baseline and 6 to 12 months ]
   High-resolution anoscopy with anal cytology testing
4. Number of Participants Who Had One or More Anal Biopsies [ Time Frame: Baseline and 6 to 12 months ]
   High resolution anoscopy and biopsy of all visible high-grade dysplastic lesions based on validated colposcopic criteria
5. Number of Participants With High-grade Anal Dysplasia Lesions [ Time Frame: Baseline and 6 to 12 months ]
   High resolution anoscopy and biopsy of all visible high-grade dysplastic lesions based on validated colposcopic criteria

Biospecimen Retention:   Samples Without DNA

Venous blood, anal swabs, vaginal swabs, high resolution anoscopy (HRA), anal biopsy samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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

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

Contacts and Locations

Locations

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

University of Pittsburgh

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Ross Cranston, M.D.; University of Pittsburgh

More Information

• Responsible Party: University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01364896
• Other Study ID Numbers: 38458
• First Posted: June 3, 2011
• Results First Posted: March 9, 2016
• Last Update Posted: May 21, 2019
• Last Verified: March 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Pittsburgh:

Non-corticosteroid immunosuppressive agent

Additional relevant MeSH terms:

Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases