A Pilot Study for Toxicity Evaluation of HIV Rectal Microbicides

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if detectable changes in permeability of the lining of the colon are caused by either application of HIV microbicide gels or medical procedures, such as flexible sigmoidoscopy.

Detailed Description
-----------------
It is not currently known if procedures used to observe the lining of the distal colon, such as endoscopy with or without pinch biopsy, may cause mucosal trauma and thus alter colonic permeability. Additionally, the application of topical HIV microbicides (to prevent HIV transmission) and shearing forces associated with rectal intercourse might also adversely affect the epithelial layer, and thus alter colonic permeability. In order to appropriately interpret testing of the effects of topical HIV microbicides on the mucosal lining of the distal colon, it is essential to understand whether these procedures themselves, adversely affect the epithelial layer. If changes in permeability can be detected, this method may be developed to help determine microbicide distribution/toxicity in early phase studies, thus improving the selection of candidate microbicides for study in larger scale clinical trials.

Official Title
-----------------
A Pilot Protocol to Determine the Effects of Chemical and Mechanical Stress on Rectal Permeability as a Surrogate for Toxicity Evaluation of Rectally Applied Microbicides

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Normosol-R
* Drug: Nonoxynol-9
* Procedure: Gastrointestinal instrumentation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Greater than or equal to 21 years of age Prior history of receptive anal intercourse (RAI) Subjects must have a history of using commercially-available personal lubricants for RAI. Ability to provide signed informed consent. Willingness to abstain from lubricant use and anal receptive intercourse for 48 hours prior to and 48 hours after Phases A and B. Willingness to use a single dose of rectally-applied N-9. Exclusion Criteria: Mental handicap or impaired cognitive performance status as judged by the investigator. Coagulation abnormality which would put the subject at risk for bleeding as judged by the Principal Investigator. History of anorectal surgery within the last month or the presence of any anorectal disease or condition that in the judgment of the investigator could affect permeability of the rectal mucosa. Presence of any painful anorectal conditions or anorectal lesions that would be tender to manipulation. History of occupational radiation exposure. History of acute or chronic diarrhea defined as three or more loose stools per day. History of any allergic response to rectal lubricants. History of sleep apnea, or airway problems with previous sedation procedures. History of significant adverse reaction to sedation medications.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nonoxynol-9<br>Gynol-II, 2% N-9, 5 mL | Drug: Nonoxynol-9<br> <br> |
| Other: Normosol-R<br>Normosol-R, 5 mL, single administration, negative control | Drug: Normosol-R<br> <br> |
| Experimental: Normosol with simulation, endoscopy and biopsy<br>Normosol-R, 5 mL following simulation, endoscopy and biopsy | Drug: Normosol-R<br> <br> Procedure: Gastrointestinal instrumentation<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-subject comparison of urine and plasma concentrations of 99mTc-DTPA |  | 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours after introduction of the treatment assignment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Microbicide, Safety, HIV prevention, HIV Seronegativity