The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 20, 2019

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.

Interventions

  • Drug: Norethisterone enantate
    • Noristerat® 200mg, solution for intramuscular injection given every 8 weeks
  • Device: Condoms
    • Latex male condoms

Arms, Groups and Cohorts

  • Experimental: Norethisterone enanthate plus 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.
  • Active Comparator: Condoms only
    • Counseling and condoms will be provided at enrolment, 1, 2, 3 and 4 months.

Clinical Trial Outcome Measures

Primary Measures

  • Time to diagnosis of recurrent BV
    • Time Frame: 6 months

Secondary Measures

  • Proportional of participants with Lactobacillus-dominant cluster
    • Time Frame: 6 months
  • Concentration of markers for inflammation
    • Time Frame: 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
    • Time Frame: 6 months

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 35 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • London School of Hygiene and Tropical Medicine
  • Collaborator
    • Imperial College London
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Suzanna C Francis, MSc MPH PHD, Principal Investigator, London School of Hygiene and Tropical Medicine

References

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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.

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