Effect of Antibiotics on Penile Microbiome and HIV Susceptibility Study in Ugandan Men

January 19, 2018 updated by: Rupert Kaul, University of Toronto

Testing the Ability of a Microbiome - Focused Intervention to Reduce HIV Susceptibility in Ugandan Men

This pilot study will assess the impact of four antimicrobial products (3 topical, one systemic) on the foreskin microbiome and HIV susceptibility of foreskin-derived CD4+ T cells. Participants will include HIV-uninfected Ugandan men presenting for elective male circumcision to reduce their HIV risk.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

RATIONALE: The foreskin is the site of most HIV acquisition in uncircumcised heterosexual men, and male circumcision (MC) reduces HIV risk by almost 60%. However, cultural and practical barriers have led to suboptimal uptake. Foreskin inflammation, defined by elevated levels of pro-inflammatory cytokines in the prepuce, is a key determinant of HIV acquisition risk in uncircumcised men, and anaerobic bacteria within the foreskin microbiome may be an important cause of this inflammation.

OBJECTIVES: A pilot in vivo - in vitro clinical study of four potential interventions to reduce HIV susceptibility in the foreskin by altering the microbiome. The study is a collaboration between the University of Toronto, IAVI-UVRI, and the Entebbe General Hospital. We will recruit 125 men presenting for elective MC, along with regular female sexual partners (if applicable). Participants will be randomized (n=25 per group) to immediate MC, or to one of four intervention arms: twice-daily application of topical metronidazole 0.75%; twice-daily application of topical clindamycin 2%; twice daily application of hydrogen peroxide 1%; or oral tinidazole 2g once a day for two days. Swabs for immune and microbiome studies will be collected before and after product. After 4 weeks the MC procedure will be performed; foreskin CD4+ T cell susceptibility to HIV will be quantified using a flow cytometry-based pseudovirus assay, and tissue immunohistochemistry performed. The primary and secondary endpoints are outlined below. A secondary study will assess the impact of penile topical antibiotic application on immunology and the microbiome in the genital tract of female sexual partners.

OUTCOMES: This in vivo - in vitro clinical trial will define the causal role of the penile microbiome in HIV susceptibility, and will assess potential strategies to take forward into HIV efficacy trials in uncircumcised heterosexual men.

Study Type

Interventional

Enrollment (Anticipated)

125

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Uganda
    • Wakiso
      • Entebbe, Wakiso, Uganda
        • Recruiting
        • UVRI-IAVI HIV Vaccine program
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Enrollment criteria include:

  1. Aged 18 years or older
  2. Biological male
  3. Uncircumcised
  4. HIV seronegative
  5. Willing to comply with the requirements of the protocol
  6. No current sexually transmitted infection (N. gonorrhoeae or C. trachomatis)
  7. No clinically relevant genital symptoms / signs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control group
25 HIV-uninfected, uncircumcised men will be immediately circumcised following enrollment. This group will serve as the comparison to the four intervention groups.
Active Comparator: Oral tinidazole group
25 HIV-uninfected, uncircumcised men will be randomized to receive oral tinidazole 2g once a day for two days.
Drug: Oral Tinidazole
Please see description under arms
Other Names:
  • FASIGYN 500mgs
Active Comparator: Topical metronidazole (0.75%) group
25 HIV-uninfected, uncircumcised men will be randomized to apply topical 0.75% metronidazole cream to the foreskin twice a day for one week, and then twice a week for three weeks.
Drug: Topical metronidazole
Please see description under arms
Other Names:
  • Rozex 0.75%
Active Comparator: Topical clindamycin (2%) group
25 HIV-uninfected, uncircumcised men will be randomized to apply topical 2% clindamycin cream to the foreskin twice a day for one week, and then twice a week for three weeks.
Drug: Topical Clindamycin
Please see description under arms
Other Names:
  • Dalacin cream 2%
Active Comparator: Topical hydrogen peroxide (1%) group
25 HIV-uninfected, uncircumcised men will be randomized to apply 1% hydrogen peroxide cream to the foreskin twice a day for one week, and then twice a week for three weeks.
Drug: Topical Hydrogen Peroxide
Please see description under arms
Other Names:
  • Crystacide 1%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
% HIV entry into foreskin derived CD4+ T cells
Time Frame: 4 weeks
This measure will utilize a validated pseudovirus entry assay.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tissue density of HIV-susceptible CD4+ T cells
Time Frame: 4 weeks
The density of CD4+ T cells in foreskin tissues will be assayed using immunohistochemistry, and the % pseudovirus entry (see primary endpoint, above) will be used to calculate the tissue density of HIV-susceptible CD4+ T cells.
4 weeks
CD4+ T cell subsets in foreskin tissue
Time Frame: 4 weeks
Immunofluorescence microscopy (IF) will be used to quantify CD4+ T cell subsets foreskin tissue after circumcision.
4 weeks
Density of Langerhans cells in foreskin tissue
Time Frame: 4 weeks
Immunofluorescence microscopy (IF) will be used to quantify Langerhans cells in foreskin tissue after circumcision.
4 weeks
Presence of foreskin inflammation
Time Frame: 4 weeks
Cytokine/chemokines will be assayed by ELISA, and foreskin inflammation defined as the presence of ≥3/7 inflammatory cytokines within the top quartile for that cytokine.
4 weeks
Foreskin microbiome composition
Time Frame: 4 weeks
The foreskin (prepuce) microbiome will be characterized based on 16S rRNA sequencing.
4 weeks
Foreskin tissue explant HIV susceptibility
Time Frame: 4 weeks
Foreskin tissue susecptibility to HIV infection will be quantified, based on p24 ELISA after ex vivo incubation with a primary HIV isolate.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toronto

Collaborators

UVRI-IAVI HIV Vaccine Program
Entebbe General Hospital

Investigators

  • Study Director: Ronald M Galiwango, MBChB/MSc, University of Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2017

Primary Completion (Anticipated)

December 7, 2019

Study Completion (Anticipated)

December 7, 2019

Study Registration Dates

First Submitted

January 19, 2018

First Submitted That Met QC Criteria

January 19, 2018

First Posted (Actual)

January 26, 2018

Study Record Updates

Last Update Posted (Actual)

January 26, 2018

Last Update Submitted That Met QC Criteria

January 19, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Penile microbiome antibiotics

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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