Vaginal Microbiome Transplantation for Recurrent Bacterial Vaginosis-A Placebo, Randomized, Controlled Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Microbiome composition
Study Overview
Brief Summary
Vaginal Microbiome Transplantation (VMT) may be beneficial in treating the most severe cases of recurrent and antibiotics-nonresponsive cases of BV. Recently, we completed a preliminary study in which we treated patients with recurrent and antibiotics-non-responsive, intractable BV, with VMT from healthy donors [Lev-Sagie, Nature Medicine 2019]. Four VMT recipients in this preliminary study featured a significant improvement of both clinical symptoms and dysbiotic vaginal microbiome composition and function, which persisted over a long follow-up period, while one recipient featured a partial remission.
The proposed study is designed as a placebo, randomized controlled trial, and is aimed to further assess whether VMT may serve as a viable option in symptomatic, intractable BV. In the suggested study, we plan to compare transplantation of: 1) vaginal fluid from healthy donors, and 2) saline (placebo).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Ages 18-50
- •Recurrent BV, defined as ≥4 symptomatic episodes of BV during the last year, who require maintenance antibiotic treatment (twice weekly) in order to remain symptom-free, or if they experienced recurrence of BV in ≤ 2 months following antibiotic treatment, with a documented history of recurrent BV in the last year.
- •Patients are otherwise healthy.
- •Contraception use
Exclusion Criteria
- •Pregnancy or a planned pregnancy in the upcoming year
- •Infection with HIV.
- •Immunodeficiency status.
Arms & Interventions
VMT recipients
In order to prevent transfer of pathogens, sperm, or antibiotic-resistant commensals we will establish a "vaginal fluid bank" in which samples from suitable donors will be kept for future use:
- Donors will be screened using a questionnaire addressing risk factors for potentially transmissible infections, undergo screening for cervico-vaginal infections, cervical cytology screening, and serology analysis for transmittable infections {see detailed screening in Lev-Sagie et al. Nat Med. 2019;25(10):1500-1504. doi: 10.1038/s41591-019-0600-6.}
- The collected samples for VMT will be examined for bacteria,viruses and sperm.
Before transplantation, patients will be treated with intravaginal antibiotics. A frozen specimen will be thawed at room temperature and will be placed in the patient's vagina.
Following VMT, patients will be evaluated every 14 days for the first month, then every month for additional 11 months.
Intervention: Vaginal Microbiome Transplantation (VMT) (Biological)
Placebo
Saline with glycerol will be used as placebo. Before transplantation, patients will be treated with intravaginal antibiotic.
Following Placebo, patients will be evaluated every 14 days for the first months, then every month for additional 2-4 months.
After 4 months, patients who initially received placebo will be offered a VMT in case they are still symptomatic and fulfill inclusion criteria, in an open-label phase.
Intervention: Placebo (Biological)
Outcomes
Primary Outcomes
Microbiome composition
Time Frame: 12 months
Characterization of the vaginal microbial community using shotgun analysis and16S rRNA sequencing
Laboratory parameters- Amsel criteria
Time Frame: 12 months
Presence or absence of each Amsel criteria (discharge, pH\>4.5, positive whiff test and clue cells on microscopy)/
Vaginal fluid microscopy
Time Frame: 12 months
Presence of Lactobacillus-dominant microbiome on microscopy
Clinical parameters- patient's complains
Time Frame: 12 months
Number of participants reporting disappearance of discharge and odor
Clinical parameters- patient's complains
Time Frame: Interim analysis at 4 months from initail intrvention, and final analysis at 12 months.
Number of participants reporting disappearance of discharge and odor
Laboratory parameters- Amsel criteria
Time Frame: Interim analysis at 4 months from initail intrvention, and final analysis at 12 months.
Presence or absence of each Amsel criteria (discharge, pH\>4.5, positive whiff test and clue cells on microscopy)/
Vaginal fluid microscopy
Time Frame: Interim analysis at 4 months from initail intrvention, and final analysis at 12 months.
Presence of Lactobacillus-dominant microbiome on microscopy
Microbiome composition
Time Frame: Interim analysis at 4 months from initail intrvention, and final analysis at 12 months.
Characterization of the vaginal microbial community using shotgun analysis and16S rRNA sequencing
Secondary Outcomes
No secondary outcomes reported
Investigators
Ahinoam Lev-Sagie
Principal investigator
Hadassah Medical Organization