The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis

Phase 4

Completed

• Conditions: Bacterial Vaginosis; HIV
• Interventions: Drug: Norethisterone enantate; Device: Condoms

• Registration Number: NCT02905890
• Lead Sponsor: London School of Hygiene and Tropical Medicine

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2016-09-09
• Study First Submitted QC: 2016-09-14
• Study First Posted: 2016-09-19
• Study Start: 2017-10-02
• Primary Completion: 2019-12-20
• Study Completion: 2019-12-20
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-10
• Last Update Posted: 2020-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 250

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Norethisterone enanthate plus condoms	Norethisterone enantate	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.
Norethisterone enanthate plus condoms	Condoms	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.
Condoms only	Condoms	Counseling and condoms will be provided at enrolment, 1, 2, 3 and 4 months.

Primary Outcome Measures

Name	Time	Method
Time to diagnosis of recurrent BV	6 months

Secondary Outcome Measures

Name	Time	Method
Proportional of participants with Lactobacillus-dominant cluster	6 months
Concentration of markers for inflammation	6 months	Twenty-four soluble immune proteins will be quantified by in-house multiplex bead immunoassay including interleukin(IL)-1α, IL1β, IL-2, IL4, IL-6, IL-7, IL- 8, IL-12, IL-15, IL16, IFN-g, MIP-1β, SDF1β, TNF-α, IP-10, RANTES, GM-CSF, G-CSF, MIG, IFN- -β, TGF-β, MCP-1, MCP-2, MIP-3α and other immune proteins as appropriate.
Acceptability of norethisterone enanthate as measured by qualitative interviews	6 months

Trial Locations

Locations (1)

MRC/UVRI Mengo Clinic and Research Station; 🇺🇬 Kampala, Uganda