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

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ClinicalTrials.gov Identifier: NCT01053741
Recruitment Status : Completed
First Posted : January 21, 2010
Results First Posted : May 25, 2017
Last Update Posted : May 25, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment
Human Immunodeficiency Virus (HIV) 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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Investigator)
Primary Purpose: Basic Science
Official Title: The Effect of Seminal Fluid on Distal Colon Mucosal Permeability and Susceptibility to HIV Infection
Study Start Date : March 2008
Primary Completion Date : December 2009
Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Normosol R
U.S. FDA Resources

Arms and Interventions

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.


Outcome Measures

Primary Outcome Measures :
  1. Epithelial Disruption Graded by a Pathologist Blinded to Study Intervention. [ Time Frame: One hour ]

    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.



Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01053741


Locations
United States, Maryland
Johns Hopkins University Drug Development Unit
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
amfAR, The Foundation for AIDS Research
Investigators
Principal Investigator: Edward Fuchs, PA-C, MBA Johns Hopkins University
More Information

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01053741     History of Changes
Other Study ID Numbers: NA_00014051
First Posted: January 21, 2010    Key Record Dates
Results First Posted: May 25, 2017
Last Update Posted: May 25, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: This is an exploratory physiologic study.

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Plasma-lyte 148
Ophthalmic Solutions
Pharmaceutical Solutions