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

This study has been completed.
Sponsor:
Collaborator:
amfAR, The Foundation for AIDS Research
Information provided by (Responsible Party):
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01053741
First received: January 20, 2010
Last updated: April 24, 2017
Last verified: April 2017

January 20, 2010
April 24, 2017
March 2008
December 2009   (Final data collection date for primary outcome measure)
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.

  • Epithelial disruption [ Time Frame: One hour ]
  • Mucosal permeability to an incorporated radioisotope as measured in plasma and urine [ Time Frame: up to 4 hours following dosing ]
Complete list of historical versions of study NCT01053741 on ClinicalTrials.gov Archive Site
Not Provided
HIV explant challenge [ Time Frame: Up to 14 days following ex vivo challenge ]
Not Provided
Not Provided
 
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.
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.
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Investigator
Primary Purpose: Basic Science
Human Immunodeficiency Virus (HIV)
  • 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: 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.
    Interventions:
    • Biological: Radiolabeled autologous seminal fluid
    • Biological: Radiolabeled Normosol-R
  • 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.
    Interventions:
    • Biological: Radiolabeled autologous seminal fluid
    • Biological: Radiolabeled Normosol-R
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
11
December 2009
December 2009   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: Male
21 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01053741
NA_00014051
Yes
Not Provided
No
This is an exploratory physiologic study.
Johns Hopkins University
Johns Hopkins University
amfAR, The Foundation for AIDS Research
Principal Investigator: Edward Fuchs, PA-C, MBA Johns Hopkins University
Johns Hopkins University
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP