Clinical trial NCT02459665: Rwanda Vaginal Microbiota Restoration Study
Official title: Preparing for a Clinical Trial of Interventions to Maintain Normal Vaginal Microbiota for Preventing Adverse Reproductive Health Outcomes in Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bacterial Vaginosis
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Rinda Ubuzima, Rwanda
First posted: 2015-06-02
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A pilot randomized controlled clinical trial of intermittent use of two different vaginal lactobacilli-containing probiotics, and oral metronidazole, to prevent bacterial vaginosis recurrence.

Detailed description: This is a pilot study to prepare for larger clinical trials. Sixty-eight HIV-negative, non-pregnant, sexually active women aged 18-45 with bacterial vaginosis (BV, by modified Amsel criteria and/or Nugent score) and/or Trichomonas vaginalis (TV, on wet mount or by culture) will be treated using oral metronidazole for 7 days. After successful treatment, and when they are free of vaginal candidiasis, other curable sexually transmitted infections (STIs) and urinary tract infection (UTI)), they will be randomised to 4 different vaginal microbiome (VMB) maintenance interventions (17 per group) within 3 days of completing oral metronidazole treatment: 1) Behavioral 'vaginal practices cessation and safer sex' counselling only (control); 2) Behavioral counselling plus 500mg metronidazole pills twice per week for two months; 3) Behavioral counselling plus Ecologic Femi vaginal capsule, once per day for 5 days immediately after oral metronidazole treatment followed by thrice weekly, for two months; 4) Group 4: Behavioral counselling plus Gynophilus vaginal tablet, once every 4 days for two months. Vaginal probiotic use may be ceased temporarily during menstruation. Participants will be asked to adhere to the interventions for 2 months, and VMB assessments will take place before (screening and enrolment visits), during (Day 7, Month 1 and Month 2 visits), and after the interventions (Month 6 visit).

Eligibility criteria: Inclusion Criteria:

* Sexually active, defined as having had sex at least twice in the two weeks prior to screening
* At high risk of HIV/STIs/BV, defined as having had more than one sexual partner in the last 12 months OR having been treated for an STI and/or BV in the last 12 months
* Successfully treated for BV (modified Amsel criteria) or TV (wet mount), and free of STIs, symptomatic vaginal candidiasis and UTI at enrollment
* Currently in good physical and mental health as judged by a study physician
* Willing and able to adhere to study procedures and provide written informed consent.

Exclusion Criteria:

* Pregnant
* HIV positive
* Clinician-observed genital ulcers, condylomata, or other genital abnormalities at screening or enrollment
* Underwent a gynaecological surgery/invasive procedure in the 3 months prior to screening
* History of significant urogenital prolapse, undiagnosed vaginal bleeding, urine or faecal incontinence, or blood clotting disorders
* Allergic to metronidazole or any other components of the study drugs
* Not willing to stop use of other oral or vaginal probiotics from the screening visit until the end of study participation
* Participating in another health intervention study
* For any other reason potentially interfering with participant safety or protocol adherence as judged by the Principal Investigator

Primary outcomes:
measure: Bacterial Vaginosis (BV) Incidence by Modified Amsel Criteria
timeFrame: 2 months (intervention period)
measure: Bacterial Vaginosis (BV) Incidence by Nugent Scoring (Nugent 7-10)
timeFrame: 2 months (intervention period)
measure: Trichomonas Vaginalis (TV) Incidence by Culture
timeFrame: 2 months (intervention period)
measure: Vaginal Candidiasis Incidence by Wet Mount Microscopy
timeFrame: 6 months: 2 months intervention period plus 4 months after intervention cessation
Secondary outcomes:
measure: Vaginal Microbiota Composition by Illumina HiSeq Sequencing: Lactobacillus Genus Concentration
timeFrame: 2 months (intervention period)
Other outcomes:
measure: Feasibility/Acceptability of Vaginal Probiotic Use by Structured Face-to-face Interview
timeFrame: 2 months (intervention period)
Locations:
Study officials:
affiliation: University of Liverpool
name: Janneke H van de Wijgert, PhD
role: STUDY_CHAIR
References:
citation: Verwijs MC, Agaba S, Umulisa MM, van de Wijgert JHHM. Feasibility and acceptability of frequent vaginal self-sampling at home by Rwandan women at high risk of urogenital tract infections. Sex Transm Infect. 2022 Feb;98(1):58-61. doi: 10.1136/sextrans-2020-054816. Epub 2021 Jan 29.
citation: Verwijs MC, Agaba S, Umulisa MM, Uwineza M, Nivoliez A, Lievens E, van de Wijgert JHHM. Vaginal probiotic adherence and acceptability in Rwandan women with high sexual risk participating in a pilot randomised controlled trial: a mixed-methods approach. BMJ Open. 2020 May 19;10(5):e031819. doi: 10.1136/bmjopen-2019-031819.
citation: Verwijs MC, Agaba SK, Darby AC, van de Wijgert JHHM. Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure. Am J Obstet Gynecol. 2020 Feb;222(2):157.e1-157.e13. doi: 10.1016/j.ajog.2019.08.008. Epub 2019 Aug 9.