Back to resultsEffect of Seminal Fluid on the Colon Wall; Implications for HIV Transmission
Primary Purpose
Human Immunodeficiency Virus (HIV)
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Radiolabeled autologous seminal fluid
Radiolabeled Normosol-R
Sponsored by
About this trial
This is an interventional basic science trial for Human Immunodeficiency Virus (HIV)
Eligibility 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.
Sites / Locations
- Johns Hopkins University Drug Development Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Seminal Fluid then Normosol
Normosol then Seminal Fluid
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01053741
First Posted
January 20, 2010
Last Updated
April 24, 2017
Sponsor
Johns Hopkins University
Collaborators
amfAR, The Foundation for AIDS Research
1. Study Identification
Unique Protocol Identification Number
NCT01053741
Brief Title
Effect of Seminal Fluid on the Colon Wall; Implications for HIV Transmission
Official Title
The Effect of Seminal Fluid on Distal Colon Mucosal Permeability and Susceptibility to HIV Infection
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
amfAR, The Foundation for AIDS Research
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus (HIV)
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Seminal Fluid then Normosol
Arm Type
Experimental
Arm Description
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.
Arm Title
Normosol then Seminal Fluid
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Radiolabeled autologous seminal fluid
Intervention Description
Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in seminal fluid vehicle.
Intervention Type
Biological
Intervention Name(s)
Radiolabeled Normosol-R
Intervention Description
Autologous lymphocytes labeled with 250 microcuries In-111 and 500 microcuries Tc-99m in Normosol-R fluid vehicle.
Primary Outcome Measure Information:
Title
Epithelial Disruption Graded by a Pathologist Blinded to Study Intervention.
Description
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.
Time Frame
One hour
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Fuchs, PA-C, MBA
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University Drug Development Unit
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
This is an exploratory physiologic study.
Learn more about this trial
Effect of Seminal Fluid on the Colon Wall; Implications for HIV Transmission
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