The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis

NCT ID: NCT02905890

Last Updated: 2020-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-02

Study Completion Date

2019-12-20

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.

Conditions

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Bacterial Vaginosis HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Norethisterone enantate

Intervention Type DRUG

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

Condoms

Intervention Type DEVICE

Latex male condoms

Condoms only

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

Group Type ACTIVE_COMPARATOR

Condoms

Intervention Type DEVICE

Latex male condoms

Interventions

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Norethisterone enantate

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

Intervention Type DRUG

Condoms

Latex male condoms

Intervention Type DEVICE

Other Intervention Names

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Noristerat

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Imperial College London

OTHER

Sponsor Role collaborator

University of Liverpool

OTHER

Sponsor Role collaborator

MRC/UVRI and LSHTM Uganda Research Unit

OTHER

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Suzanna C Francis, MSc MPH PHD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Locations

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MRC/UVRI Mengo Clinic and Research Station

Kampala, , Uganda

Site Status

Countries

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Uganda

References

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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.

Reference Type BACKGROUND
PMID: 24832618 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16652274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26253744 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24023807 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26219949 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25612136 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24840644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24413042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23014519 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23523018 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16856087 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27500670 (View on PubMed)

Other Identifiers

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QA906

Identifier Type: -

Identifier Source: org_study_id

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