Rwanda Vaginal Microbiota Restoration Study

Not Applicable

Completed

Conditions: Bacterial Vaginosis

Interventions: Drug: Prophylactic use of metronidazole pills (500 mg)
Biological: Vaginal Lcr35-containing probiotic for prevention of BV recurrence
Biological: Vaginal multiple lactobacilli-containing probiotic for prevention of BV recurrence

Registration Number: NCT02459665

Lead Sponsor: Janneke van de Wijgert

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 68

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2	Prophylactic use of metronidazole pills (500 mg)	Positive control group: After initial treatment for BV/TV, metronidazole pills (500 mg) twice per week for 2 months.
Group 4	Vaginal Lcr35-containing probiotic for prevention of BV recurrence	After initial treatment for BV/TV, Gynophilus LP vaginal tablet (a vaginal probiotic) once every 4 days for two months.
Group 3	Vaginal multiple lactobacilli-containing probiotic for prevention of BV recurrence	After initial treatment for BV/TV, Ecologic Femi+ vaginal capsule (a vaginal probiotic) once per day for 5 days immediately after the initial treatment followed by thrice weekly for two months.

Primary Outcome Measures

Name	Time	Method
Trichomonas Vaginalis (TV) Incidence by Culture	2 months (intervention period)	A swab was inoculated into an InPouch culture pouch, specifically designed for TV growth. The pouch was checked daily for five days to detect growth. The results was positive when growth detected and negative when no growth detected on the fifth day. Intent-to-treat (ITT) analyses, using person-years (PY) at risk as the denominator for each incidence rate.
Bacterial Vaginosis (BV) Incidence by Modified Amsel Criteria	2 months (intervention period)	Modified Amsel criteria positive is at least 2 of 3 of the following positive: clue cells, vaginal pH, whiff test. Modified intent-to-treat (ITT) analyses (women with Nugent 7-10 at enrollment excluded), using person-years (PY) at risk as denominator of each incidence rate.
Bacterial Vaginosis (BV) Incidence by Nugent Scoring (Nugent 7-10)	2 months (intervention period)	The Nugent score is a scale from 0-10 based on visualisation of three different bacterial morphotypes on a Gram stained slide, but in the incidence rates, the variable was used as a binary variable: BV present (Nugent score 7-10) or absent (Nugent score 0-6). Modified intent-to-treat (ITT) analyses (women with Nugent 7-10 at enrollment excluded), using person-years (PY) at risk as the denominator for each incidence rate.
Vaginal Candidiasis Incidence by Wet Mount Microscopy	6 months: 2 months intervention period plus 4 months after intervention cessation	A wet mount is a smear of vaginal fluid on a microscopy slide, which is examined under a microscope. Yeasts are visible without staining. The definition of vaginal candidiasis was any yeast visible on the wet mount. Symptomatic vaginal candidiasis was considered a safety outcome because treatment of bacterial vaginosis often results in vaginal candidiasis. Intent-to-treat (ITT) analysis with person-years (PY) at risk as the denominator of all incidence rates.

Secondary Outcome Measures

Name	Time	Method
Vaginal Microbiota Composition by Illumina HiSeq Sequencing: Lactobacillus Genus Concentration	2 months (intervention period)	The vaginal microbiota sequencing results are exploratory and full data can be found in a manuscript on the BioRxiv preprint server. The most important outcome is the concentration of Lactobacillus genus in vaginal samples taken at the end of the intervention period (M2 visit).