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

NCT03412071 | Unknown

• 1 other identifier: Penile microbiome antibiotics
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Foreskin HIV Susceptibility

Outcome Measures

Primary Outcomes (1)

• % HIV entry into foreskin derived CD4+ T cells

  This measure will utilize a validated pseudovirus entry assay.

  4 weeks

Secondary Outcomes (6)

• Tissue density of HIV-susceptible CD4+ T cells

  4 weeks

• CD4+ T cell subsets in foreskin tissue

  4 weeks

• Density of Langerhans cells in foreskin tissue

  4 weeks

• Presence of foreskin inflammation

  4 weeks

• Foreskin microbiome composition

  4 weeks

Study Arms (5)

Control group

NO INTERVENTION

25 HIV-uninfected, uncircumcised men will be immediately circumcised following enrollment. This group will serve as the comparison to the four intervention groups.

Oral tinidazole group

ACTIVE COMPARATOR

25 HIV-uninfected, uncircumcised men will be randomized to receive oral tinidazole 2g once a day for two days.

Drug: Oral Tinidazole

Topical metronidazole (0.75%) group

ACTIVE COMPARATOR

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

Topical clindamycin (2%) group

ACTIVE COMPARATOR

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

Topical hydrogen peroxide (1%) group

ACTIVE COMPARATOR

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

Interventions

Oral Tinidazole DRUG

Please see description under arms

Also known as: FASIGYN 500mgs

Oral tinidazole group

Topical metronidazole DRUG

Please see description under arms

Also known as: Rozex 0.75%

Topical metronidazole (0.75%) group

Topical Clindamycin DRUG

Please see description under arms

Also known as: Dalacin cream 2%

Topical clindamycin (2%) group

Topical Hydrogen Peroxide DRUG

Please see description under arms

Also known as: Crystacide 1%

Topical hydrogen peroxide (1%) group

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Foreskin HIV susceptibility can only be assessed in biological males.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Toronto: lead
• UVRI-IAVI HIV Vaccine Program: collaborator
• Entebbe General Hospital: collaborator

Study Sites (1)

UVRI-IAVI HIV Vaccine Program

Entebbe, Wakiso, Uganda

RECRUITING

Related Publications (22)

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• Prodger JL, Gray R, Kigozi G, Nalugoda F, Galiwango R, Hirbod T, Wawer M, Hofer SO, Sewankambo N, Serwadda D, Kaul R. Foreskin T-cell subsets differ substantially from blood with respect to HIV co-receptor expression, inflammatory profile, and memory status. Mucosal Immunol. 2012 Mar;5(2):121-8. doi: 10.1038/mi.2011.56. Epub 2011 Nov 16.

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• Prodger JL, Hirbod T, Kigozi G, Nalugoda F, Reynolds SJ, Galiwango R, Shahabi K, Serwadda D, Wawer MJ, Gray RH, Kaul R; Rakai Genital Immunology Research Group. Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda. Mucosal Immunol. 2014 May;7(3):634-44. doi: 10.1038/mi.2013.83. Epub 2013 Oct 23.

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• Menard JP. Antibacterial treatment of bacterial vaginosis: current and emerging therapies. Int J Womens Health. 2011;3:295-305. doi: 10.2147/IJWH.S23814. Epub 2011 Aug 23.

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• TenoRes Study Group. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Lancet Infect Dis. 2016 May;16(5):565-575. doi: 10.1016/S1473-3099(15)00536-8. Epub 2016 Jan 29. Erratum In: Lancet Infect Dis. 2016 Jun;16(6):636. doi: 10.1016/S1473-3099(16)30089-5. Lancet Infect Dis. 2018 Jan;18(1):21. doi: 10.1016/S1473-3099(17)30723-5.

  PMID: 26831472 BACKGROUND

• Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005 Nov;2(11):e298. doi: 10.1371/journal.pmed.0020298. Epub 2005 Oct 25.

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• Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007 Feb 24;369(9562):643-56. doi: 10.1016/S0140-6736(07)60312-2.

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• Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007 Feb 24;369(9562):657-66. doi: 10.1016/S0140-6736(07)60313-4.

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• Sgaier SK, Reed JB, Thomas A, Njeuhmeli E. Achieving the HIV prevention impact of voluntary medical male circumcision: lessons and challenges for managing programs. PLoS Med. 2014 May 6;11(5):e1001641. doi: 10.1371/journal.pmed.1001641. eCollection 2014 May.

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• Kigozi G, Wawer M, Ssettuba A, Kagaayi J, Nalugoda F, Watya S, Mangen FW, Kiwanuka N, Bacon MC, Lutalo T, Serwadda D, Gray RH. Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters). AIDS. 2009 Oct 23;23(16):2209-13. doi: 10.1097/QAD.0b013e328330eda8.

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  PMID: 31324206 DERIVED

MeSH Terms

Interventions

Tinidazole; Metronidazole; Clindamycin; Hydrogen Peroxide

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lincomycin; Lincosamides; Pyrrolidines; Glycosides; Carbohydrates; Peroxides; Oxides; Anions; Ions; Electrolytes; Inorganic Chemicals; Reactive Oxygen Species; Free Radicals; Oxygen Compounds

Study Officials

• Rupert Kaul, MD/PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

• Ronald M Galiwango, MBChB/MSc

  University of Toronto

  STUDY DIRECTOR

Central Study Contacts

Rupert Kaul, MD/PhD

CONTACT

(416) 946-7054; rupert.kaul@utoronto.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - Principal Investigator

Model Details: Randomized, open label with 5 arms

Study Record Dates

• First Submitted: January 19, 2018
• First Posted: January 26, 2018
• Study Start: December 7, 2017
• Primary Completion: December 7, 2019
• Study Completion: December 7, 2019
• Last Updated: January 26, 2018

Record last verified: 2018-01

Locations

UG (1)