The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Bacterial Vaginosis, HIV

Intervention / Treatment
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* Drug: Norethisterone enantate
* Device: Condoms


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Norethisterone enanthate plus condoms<br>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<br>* Noristerat® 200mg, solution for intramuscular injection given every 8 weeks<br>* Other names: Noristerat;Device: Condoms<br>* Latex male condoms<br>|
| Active Comparator: Condoms only<br>Counseling and condoms will be provided at enrolment, 1, 2, 3 and 4 months. | Device: Condoms<br>* Latex male condoms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to diagnosis of recurrent BV |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportional of participants with Lactobacillus-dominant cluster |  | 6 months | 
| Concentration of markers for inflammation | 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. | 6 months | 
| Acceptability of norethisterone enanthate as measured by qualitative interviews |  | 6 months |