Trial of Male Circumcision: HIV, Sexually Transmitted Disease (STD) and Behavioral Effects in Men, Women and the Community

NCT00124878 | Unknown Phase 3 DMC

• 1 other identifier: 22006
• Study Type: interventional
• Target: 5,200
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized controlled trial conducted in Rakai District, Uganda, has enrolled 997 HIV positive men and 500 men who declined to learn HIV results (regardless of HIV status). The hypotheses are that male circumcision will be acceptable to and safe in both groups and will reduce the rates of STD acquisition in both groups and of HIV acquisition in HIV-negative men. Enrollment was ended on Dec 12, 2006, following an interim Data Monitoring and Safety Board (DSMB) review of a closed report. At that time the DSMB determined that futility with respect to the female HIV outcome. There was an non-significantly higher rate of HIV acquisition in women partners of HIV+ men in couples who had resumed sex prior to certified post-surgical wound healing. The data indicated significant reductions (\~50%) in GUD symptoms among circumcised HIV+ men. The DSMB recommended: 1) that men and women should continue to be followed in complete two year follow up on all, 2) that circumcision for remaining HIV+ intervention arm men and for control arm men who had completed their 2 year follow should continue, contingent on a) revision of the study protocol to add additional post-surgical visits to assess wound healing, b) protocol revision to further strengthen education for both male and female partners on the need to postpone sex until certified wound healing, and c) approval of the revised protocol by the IRBs in both the US and Uganda. 3) An additional follow up visit for women be instituted at 18 months after enrollment. Protocol revision and IRB approvals have been finalized in June, 2007. The study has also enrolled and is following 3,700 women sexual partners of men enrolled in this study and in a complementary National Institutes of Health (NIH) funded study (U1 AI51171 which is separately registered). The hypotheses are that male circumcision will be acceptable to and safe in women partners, and will reduce the women's acquisition of HIV and STDs such as herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV).

Conditions

HIV Infections; Sexually Transmitted Diseases; Papillomavirus Infections; Genital Herpes; Gonorrhea; Chlamydia Infections; Syphilis; Bacterial Vaginosis

Keywords

HIV; STDs; Male circumcision; HIV+ males; HIV-negative males; Female partners; STDs such as the following:; HPV; HSV-2; HIV Seronegativity

Outcome Measures

Primary Outcomes (2)

• Rates of HIV acquisition in HIV-negative (neg) males and HIV-neg female partners

• Rates of STD acquisition in HIV-neg and HIV positive (+) males and HIV-neg and HIV+ female partners

Secondary Outcomes (3)

• Circumcision safety in HIV+ and HIV-neg males

• Behaviors among males and females in couples where the male is randomized to immediate versus delayed circumcision

• Behaviors among men and women in the general community

Study Arms (2)

Arm 1 Male circumcision

ACTIVE COMPARATOR

Men receive circumcision after randomization; procedure is generally provided within two weeks. A man randomized to the intervention arm who then declines circumcision for 6 or more months is considered a cross over.

Procedure: Male circumcision

Arm 2

NO INTERVENTION

Men wait for two years of follow up before being offered male circumcision

Procedure: Male circumcision

Interventions

Male circumcision PROCEDURE

Sleeve circumcision

Arm 1 Male circumcision; Arm 2

Eligibility Criteria

• Age: 15 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• MALES randomized to circumcision:
• Age 15-49
• Able and willing to provide written informed consent
• Have no medical contraindications to male circumcision
• FEMALE partners:
• Able and willing to provide written informed consent
• No age limit

You may not qualify if:

• Medical contraindications, including penile pathology or anemia (males). Unable or unwilling to provide informed consent.
• Please note: for participants under age 18, the study follows informed consent/assent procedures as required under US Federal Regulations. The latter are also consistent with Ugandan policy.

Sponsors & Collaborators

• Wawer, Maria J., M.D.: lead
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator
• Rakai Health Sciences Program: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator

Study Sites (1)

Rakai Health Sciences Program

Kalisizo, Rakai District, Uganda

Location

Related Publications (9)

• Tobian AA, Kong X, Wawer MJ, Kigozi G, Gravitt PE, Serwadda D, Eaton KP, Nalugoda F, Quinn TC, Gray RH. Circumcision of HIV-infected men and transmission of human papillomavirus to female partners: analyses of data from a randomised trial in Rakai, Uganda. Lancet Infect Dis. 2011 Aug;11(8):604-12. doi: 10.1016/S1473-3099(11)70038-X. Epub 2011 Apr 12.

  PMID: 21489882 DERIVED

• Wawer MJ, Tobian AA, Kigozi G, Kong X, Gravitt PE, Serwadda D, Nalugoda F, Makumbi F, Ssempiija V, Sewankambo N, Watya S, Eaton KP, Oliver AE, Chen MZ, Reynolds SJ, Quinn TC, Gray RH. Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda. Lancet. 2011 Jan 15;377(9761):209-18. doi: 10.1016/S0140-6736(10)61967-8. Epub 2011 Jan 6.

  PMID: 21216000 DERIVED

• Serwadda D, Wawer MJ, Makumbi F, Kong X, Kigozi G, Gravitt P, Watya S, Nalugoda F, Ssempijja V, Tobian AA, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Oliver AE, Iga B, Laeyendecker O, Gray RH. Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda. J Infect Dis. 2010 May 15;201(10):1463-9. doi: 10.1086/652185.

  PMID: 20370481 DERIVED

• Gray RH, Serwadda D, Tobian AA, Chen MZ, Makumbi F, Suntoke T, Kigozi G, Nalugoda F, Iga B, Quinn TC, Moulton LH, Laeyendecker O, Reynolds SJ, Kong X, Wawer MJ. Effects of genital ulcer disease and herpes simplex virus type 2 on the efficacy of male circumcision for HIV prevention: Analyses from the Rakai trials. PLoS Med. 2009 Nov;6(11):e1000187. doi: 10.1371/journal.pmed.1000187. Epub 2009 Nov 24.

  PMID: 19936044 DERIVED

• Wawer MJ, Makumbi F, Kigozi G, Serwadda D, Watya S, Nalugoda F, Buwembo D, Ssempijja V, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Opendi P, Iga B, Ridzon R, Laeyendecker O, Gray RH. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet. 2009 Jul 18;374(9685):229-37. doi: 10.1016/S0140-6736(09)60998-3.

  PMID: 19616720 DERIVED

• Kiggundu V, Watya S, Kigozi G, Serwadda D, Nalugoda F, Buwembo D, Settuba A, Anyokorit M, Nkale J, Kighoma N, Ssempijja V, Wawer M, Gray RH. The number of procedures required to achieve optimal competency with male circumcision: findings from a randomized trial in Rakai, Uganda. BJU Int. 2009 Aug;104(4):529-32. doi: 10.1111/j.1464-410X.2009.08420.x. Epub 2009 Apr 21.

  PMID: 19389002 DERIVED

• Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, Charvat B, Ssempijja V, Riedesel M, Oliver AE, Nowak RG, Moulton LH, Chen MZ, Reynolds SJ, Wawer MJ, Gray RH. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009 Mar 26;360(13):1298-309. doi: 10.1056/NEJMoa0802556.

  PMID: 19321868 DERIVED

• Tobian AA, Charvat B, Ssempijja V, Kigozi G, Serwadda D, Makumbi F, Iga B, Laeyendecker O, Riedesel M, Oliver A, Chen MZ, Reynolds SJ, Wawer MJ, Gray RH, Quinn TC. Factors associated with the prevalence and incidence of herpes simplex virus type 2 infection among men in Rakai, Uganda. J Infect Dis. 2009 Apr 1;199(7):945-9. doi: 10.1086/597074.

  PMID: 19220138 DERIVED

• Kigozi G, Gray RH, Wawer MJ, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Ridzon R, Opendi P, Sempijja V, Settuba A, Buwembo D, Kiggundu V, Anyokorit M, Nkale J, Kighoma N, Charvat B. The safety of adult male circumcision in HIV-infected and uninfected men in Rakai, Uganda. PLoS Med. 2008 Jun 3;5(6):e116. doi: 10.1371/journal.pmed.0050116.

  PMID: 18532873 DERIVED

MeSH Terms

Conditions

HIV Infections; Sexually Transmitted Diseases; Papillomavirus Infections; Herpes Genitalis; Gonorrhea; Chlamydia Infections; Syphilis; Vaginosis, Bacterial

Interventions

Circumcision, Male

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; DNA Virus Infections; Tumor Virus Infections; Herpes Simplex; Herpesviridae Infections; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Male; Male Urogenital Diseases; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sexually Transmitted Diseases, Bacterial; Chlamydiaceae Infections; Treponemal Infections; Spirochaetales Infections; Vaginitis; Vaginal Diseases

Intervention Hierarchy (Ancestors)

Body Modification, Non-Therapeutic; Cosmetic Techniques; Therapeutics; Surgical Procedures, Operative; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• David Serwadda, MBChB,MPH

  Makerere University Institute of Public Health, Kampala

  PRINCIPAL INVESTIGATOR

• Godfrey Kigozi, MBChB, MPH

  Rakai Health Sciences Program

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV

Study Record Dates

• First Submitted: July 25, 2005
• First Posted: July 28, 2005
• Study Start: August 1, 2003
• Study Completion: September 1, 2009
• Last Updated: August 10, 2007

Record last verified: 2005-07

Locations

UG (1)