The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis

HIV Clinical Trial

— HCBV  

Official title:

Hormonal Contraception and Bacterial Vaginosis (HCBV): The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis Among Women at High Risk for HIV Infection in Kampala, Uganda

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02905890
• Other study ID #: QA906
• Status: Completed
• Phase: Phase 4
• Start date: October 2, 2017
• Est. completion date: December 20, 2019

Study information

• Verified date: March 2020
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Bacterial vaginosis (BV) is highly prevalent among women in Africa and is associated with HIV acquisition. BV has been described as a dysbiosis, or a microbial imbalance, and is treated with metronidazole; however, once treated, it often recurs rapidly. Developing robust treatment strategies to prevent recurrent BV is important for HIV prevention in key populations at high risk for HIV infection.

There is evidence that hormonal contraceptives, including depot medroxyprogesterone acetate (DMPA), decrease BV recurrence; however, there is also evidence that DMPA increases the risk of HIV infection. Encouraging women to start or switch to an alternative progestin injectable such as norethisterone enantate (NET-EN) may mitigate HIV risk whilst decreasing the risk of recurrent BV. To date, there are no published studies that have investigated the effect of NET-EN on vaginal microbiota.

The proposed study 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 the Good Health for Women Project in Kampala, Uganda. Consenting and eligible women will be treated for BV, and randomised to either NET-EN plus condoms or condoms only. Women currently using DMPA will be enrolled as an observational comparison arm. All participants will be interviewed and examined; samples for vaginal microbiota, sexually transmitted infections, and inflammatory markers will be obtained. Women will be followed up after 1 week, and 1, 2, 3, 4 and 6 months. The primary outcomes will be differences in vaginal microbiota clusters, time to recurrent BV, and inflammatory markers. Qualitative research will be carried out to assess the acceptability of, and adherence to, NET-EN.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: December 20, 2019
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• BV positive by Nugent score

• HIV negative

• Capable of providing written informed consent

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Bacterial Vaginosis
• HIV
• Vaginal Diseases
• Vaginosis, Bacterial

Intervention

Drug:
• Norethisterone enantate
Noristerat® 200mg, solution for intramuscular injection given every 8 weeks

Device:
• Condoms
Latex male condoms

Locations

Country	Name	City	State
Uganda	MRC/UVRI Mengo Clinic and Research Station	Kampala

Sponsors (4)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Imperial College London, MRC/UVRI Uganda Research Unit on Aids, University of Liverpool

Country where clinical trial is conducted

Uganda, 

References & Publications (12)

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. Review. — View Citation

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. Epub 2006 Apr 26. — View Citation

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. — View Citation

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. French. — View Citation

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;(3):CD005214. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to diagnosis of recurrent BV		6 months
Secondary	Proportional of participants with Lactobacillus-dominant cluster		6 months
Secondary	Concentration of markers for inflammation	Twenty-four soluble immune proteins will be quantified by in-house multiplex bead immunoassay including interleukin(IL)-1a, IL1ß, IL-2, IL4, IL-6, IL-7, IL- 8, IL-12, IL-15, IL16, IFN-g, MIP-1ß, SDF1ß, TNF-a, IP-10, RANTES, GM-CSF, G-CSF, MIG, IFN- -ß, TGF-ß, MCP-1, MCP-2, MIP-3a and other immune proteins as appropriate.	6 months
Secondary	Acceptability of norethisterone enanthate as measured by qualitative interviews		6 months