Effect of Seminal Fluid on the Colon Wall; Implications for HIV Transmission

The Effect of Seminal Fluid on Distal Colon Mucosal Permeability and Susceptibility to HIV Infection

This research is being done to learn how seminal fluid affects the lining of the colon, and whether this might make it easier for HIV to get into the body and cause infection.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Biological: Radiolabeled autologous seminal fluid; Biological: Radiolabeled Normosol-R

Detailed Description

Design of effective rectal microbicides to prevent HIV infection requires an understanding of rectal HIV transmission and the location within the lower gastrointestinal (GI) tract (luminal and mucosal) of HIV (cell-free and cell-associated) following exposure to infected seminal fluid. These basic details of HIV transmission have yet to be determined in human subjects, yet they are essential to select microbicide candidates if they are to be rationally designed to achieve effective concentrations at sites of HIV transmission. Rational development of a rectal microbicide also requires an understanding of those factors that may contribute to colonic mucosal injury - potential confounders of microbicidal effect. Such factors include exposure to seminal fluid which has been shown in animal and in vitro studies to cause histologic and permeability changes that might facilitate HIV transmission.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Drug Development Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Able to provide signed informed consent
• Men of 21 years or older.
• Prior history of receptive anal intercourse.
• Laboratory values within the last 28 days:
• Negative for HIV antibodies
• Lymphocyte count within normal limits
• Neutrophil count > 1,000 cells/ml
• Cluster of Differentiation 4 (CD4) cell count > 500 cells/ml
• Platelet count ≥ 150,000 cells/mm3
• Prothrombin Time (PT) within normal limits
• Partial thromboplastin time (PTT) within normal limits.
• No childbearing intentions.

Exclusion Criteria:

• Active anorectal disease or recent (3 months) anorectal surgery;
• Diarrhea, defined as three or more loose stools per day, for at least three days prior to admission.
• History of sleep apnea, or airway problems with previous sedation procedures.
• History of significant adverse reaction to sedation medications.
• Other history, including significant occupational radiation exposure, history of inflammatory bowel disease or any other diseases and lab results, such that, in the judgment of the investigator, study procedures are not considered safe for the subject's participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Seminal Fluid then Normosol; 2.5 mL radiolabeled autologous seminal fluid administered rectally x1. Two week pause between interventions. Then 2.5 mL radiolabeled Normosol-R administered rectally X1.	Biological: Radiolabeled autologous seminal fluid; Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in seminal fluid vehicle.; Biological: Radiolabeled Normosol-R; Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in Normosol-R fluid vehicle.
Experimental: Normosol then Seminal Fluid; 2.5 mL radiolabeled Normosol-R administered rectally x1. Two week pause between interventions. Then 2.5 mL radiolabeled autologous seminal fluid administered rectally X1.	Biological: Radiolabeled autologous seminal fluid; Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in seminal fluid vehicle.; Biological: Radiolabeled Normosol-R; Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in Normosol-R fluid vehicle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epithelial Disruption Graded by a Pathologist Blinded to Study Intervention.	Endoscopy will be performed to obtain biopsy specimens at baseline and following each inpatient enema exposure. Samples will be obtained at each flexible sigmoidoscopy and set aside for batch sectioning and H&E staining. Slides will be reviewed and scored by a qualified pathologist blinded to treatment assignment using a qualitative scoring system. This scoring system uses semi-quantitative scoring that focuses on acute toxicity to epithelial cell layer similar to that seen in animal studies. This is a categorical grading scale, where 0 = Epithelial surface intact;1 = <1/3 of surface denuded; 2 = 1/3 - 2/3rds of surface denuded;3 = More than 2/3rds of surface denuded. Six separate biopsies for each subject and each treatment intervention were analyzed in a multi-level analysis. In comparison with the baseline condition (no intervention), the odds and 95% confidence interval (CI) of having a higher epithelial denudation score were calculated for each intervention.	One hour

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: amfAR, The Foundation for AIDS Research
• Investigators: Principal Investigator: Edward Fuchs, PA-C, MBA, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: January 20, 2010
• First Submitted That Met QC Criteria: January 20, 2010
• First Posted (Estimate): January 21, 2010

Study Record Updates

• Last Update Posted (Actual): May 25, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: NA_00014051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is an exploratory physiologic study.