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

Human Immunodeficiency Virus (HIV) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01053741
• Other study ID #: NA_00014051
• Status: Completed
• Phase: N/A
• First received: January 20, 2010
• Last updated: October 2, 2014
• Start date: March 2008
• Est. completion date: December 2009

Study information

• Verified date: October 2014
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Able to provide signed informed consent

2. Men of 21 years or older.

3. Prior history of receptive anal intercourse.

4. Laboratory values within the last 28 days:

• Negative for HIV antibodies

• Lymphocyte count within normal limits

• Neutrophil count > 1,000 cells/ml

• CD4 > 500 cells/ml

• Platelet count = 150,000 cells/mm3

• PT within normal limits

• PTT within normal limits.

5. No childbearing intentions.

Exclusion Criteria:

1. Active anorectal disease or recent (3 months) anorectal surgery;

2. Diarrhea, defined as three or more loose stools per day, for at least three days prior to admission.

3. History of sleep apnea, or airway problems with previous sedation procedures.

4. History of significant adverse reaction to sedation medications.

5. 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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus (HIV)
• Immunologic Deficiency Syndromes

Intervention

Biological:
• Autologous seminal fluid with Tc-99m/In-111 radiolabels
Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in seminal fluid vehicle.

Other:
• Autologous lymphocytes labeled with In-111 in normosol vehicle with TC-99m DTPA incorporated
Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in Normosol-R fluid vehicle.

Locations

Country	Name	City	State
United States	Johns Hopkins University Drug Development Unit	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	amfAR, The Foundation for AIDS Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epithelial disruption		One hour	Yes
Primary	Mucosal permeability to an incorporated radioisotope as measured in plasma and urine		up to 4 hours following dosing	Yes
Secondary	HIV explant challenge		Up to 14 days following ex vivo challenge	Yes