The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis

NCT02905890 | Completed Phase 4 DMC

• 1 other identifier: QA906
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study, Hormonal Contraception \& BV (HCBV), will investigate the effect of NET-EN and DMPA on recurrent BV, vaginal microbiota and inflammatory markers among women at high risk for HIV in Kampala, Uganda. The hypothesis is that NET-EN will show a similar beneficial effect on recurrent BV and vaginal microbiota as DMPA, without inducing signs of mucosal inflammation.

Conditions

Bacterial Vaginosis; HIV

Outcome Measures

Primary Outcomes (1)

• Time to diagnosis of recurrent BV

  6 months

Secondary Outcomes (3)

• Proportional of participants with Lactobacillus-dominant cluster

  6 months

• Concentration of markers for inflammation

  6 months

• Acceptability of norethisterone enanthate as measured by qualitative interviews

  6 months

Study Arms (2)

Norethisterone enanthate plus condoms

EXPERIMENTAL

200 mg Norethisterone enanthate intramuscularly every eight weeks at enrolment, 2 and 4 months. Counseling and condoms will be provided at enrolment, 1, 2, 3 and 4 months.

Drug: Norethisterone enantate; Device: Condoms

Condoms only

ACTIVE COMPARATOR

Counseling and condoms will be provided at enrolment, 1, 2, 3 and 4 months.

Device: Condoms

Interventions

Norethisterone enantate DRUG

Noristerat® 200mg, solution for intramuscular injection given every 8 weeks

Also known as: Noristerat

Norethisterone enanthate plus condoms

Condoms DEVICE

Latex male condoms

Condoms only; Norethisterone enanthate plus condoms

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BV positive by Nugent score
• HIV negative
• Capable of providing written informed consent

You may not qualify if:

• Currently pregnant or using a reliable contraception (e.g. injectables, intrauterine devices, implant, oral contraceptive pills)
• Desiring pregnancy in the next year
• History of tubal ligation or hysterectomy
• Contraindication to progestin-only contraceptives
• Unable to comprehend consent material because of language barrier or psychological difficulty

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Imperial College London: collaborator
• University of Liverpool: collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator

Study Sites (1)

MRC/UVRI Mengo Clinic and Research Station

Kampala, Uganda

Location

Related Publications (12)

• Mitchell C, Marrazzo J. Bacterial vaginosis and the cervicovaginal immune response. Am J Reprod Immunol. 2014 Jun;71(6):555-63. doi: 10.1111/aji.12264.

  PMID: 24832618 BACKGROUND

• Bradshaw CS, Morton AN, Hocking J, Garland SM, Morris MB, Moss LM, Horvath LB, Kuzevska I, Fairley CK. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006 Jun 1;193(11):1478-86. doi: 10.1086/503780. Epub 2006 Apr 26.

  PMID: 16652274 BACKGROUND

• Francis SC, Looker C, Vandepitte J, Bukenya J, Mayanja Y, Nakubulwa S, Hughes P, Hayes RJ, Weiss HA, Grosskurth H. Bacterial vaginosis among women at high risk for HIV in Uganda: high rate of recurrent diagnosis despite treatment. Sex Transm Infect. 2016 Mar;92(2):142-8. doi: 10.1136/sextrans-2015-052160. Epub 2015 Aug 7.

  PMID: 26253744 BACKGROUND

• Vodstrcil LA, Hocking JS, Law M, Walker S, Tabrizi SN, Fairley CK, Bradshaw CS. Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis. PLoS One. 2013 Sep 4;8(9):e73055. doi: 10.1371/journal.pone.0073055. eCollection 2013.

  PMID: 24023807 BACKGROUND

• Bradshaw CS, Brotman RM. Making inroads into improving treatment of bacterial vaginosis - striving for long-term cure. BMC Infect Dis. 2015 Jul 29;15:292. doi: 10.1186/s12879-015-1027-4.

  PMID: 26219949 BACKGROUND

• Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, Van Damme L, Delany-Moretlwe S, Francis SC, Friedland BA, Hayes RJ, Heffron R, Kapiga S, Karim QA, Karpoff S, Kaul R, McClelland RS, McCormack S, McGrath N, Myer L, Rees H, van der Straten A, Watson-Jones D, van de Wijgert JH, Stalter R, Low N. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med. 2015 Jan 22;12(1):e1001778. doi: 10.1371/journal.pmed.1001778. eCollection 2015 Jan.

  PMID: 25612136 BACKGROUND

• Govender Y, Avenant C, Verhoog NJ, Ray RM, Grantham NJ, Africander D, Hapgood JP. The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor. PLoS One. 2014 May 19;9(5):e96497. doi: 10.1371/journal.pone.0096497. eCollection 2014.

  PMID: 24840644 BACKGROUND

• Morrison C, Fichorova RN, Mauck C, Chen PL, Kwok C, Chipato T, Salata R, Doncel GF. Cervical inflammation and immunity associated with hormonal contraception, pregnancy, and HIV-1 seroconversion. J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):109-17. doi: 10.1097/QAI.0000000000000103.

  PMID: 24413042 BACKGROUND

• Butler AR, Smith JA, Polis CB, Gregson S, Stanton D, Hallett TB. Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk. AIDS. 2013 Jan 2;27(1):105-113. doi: 10.1097/QAD.0b013e32835a5a52.

  PMID: 23014519 BACKGROUND

• Devoize JL, Sztark G, Mehou-Loko A, Foo Cheung L, Joyes B. [Neurological manifestation of multiple cholesterol embolization syndrome: Value of MRI diffusion sequence]. Rev Neurol (Paris). 2013 Nov;169(11):913-6. doi: 10.1016/j.neurol.2012.11.006. Epub 2013 Mar 21. No abstract available. French.

  PMID: 23523018 BACKGROUND

• Draper BH, Morroni C, Hoffman M, Smit J, Beksinska M, Hapgood J, Van der Merwe L. Depot medroxyprogesterone versus norethisterone oenanthate for long-acting progestogenic contraception. Cochrane Database Syst Rev. 2006 Jul 19;2006(3):CD005214. doi: 10.1002/14651858.CD005214.pub2.

  PMID: 16856087 BACKGROUND

• Polis CB, Curtis KM, Hannaford PC, Phillips SJ, Chipato T, Kiarie JN, Westreich DJ, Steyn PS. An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women. AIDS. 2016 Nov 13;30(17):2665-2683. doi: 10.1097/QAD.0000000000001228.

  PMID: 27500670 BACKGROUND

MeSH Terms

Conditions

Vaginosis, Bacterial

Interventions

norethindrone enanthate; Condoms

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Contraceptive Devices, Male; Contraceptive Devices; Equipment and Supplies

Study Officials

• Suzanna C Francis, MSc MPH PHD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 19, 2016
• Study Start: October 2, 2017
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: March 12, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

UG (1)