Vaginal Microbiome Transplantation for Recurrent Bacterial Vaginosis

Vaginal Microbiome Transplantation for Recurrent Bacterial Vaginosis-A Placebo, Randomized, Controlled Trial

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) autologous transplantation, of the patient's own vaginal fluid.

Study Overview

• Status: Recruiting
• Conditions: Bacterial Vaginoses
• Intervention / Treatment: Biological: Placebo; Biological: Vaginal Microbiome Transplantation (VMT)

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ahinoam Lev-Sagie; Phone Number: +972544327178; Email: levsagie@netvision.net.il

Study Locations

• Israel
  • Jerusalem, Israel, 9765422
    • Recruiting
    • Hadassah Medical Center
    • Contact: Ahinoam Lev-Sagie, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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 2 months, then every month for additional 10 months.	Biological: Vaginal Microbiome Transplantation (VMT); Healthy donors vaginal fluid is introduced into recipients' vagina to replace their indigenous disease-associated microbiome
Placebo Comparator: Placebo; Vaginal fluid of all recipients will be collected before initiation of the study using the same protocol, will be clearly labeled and will be kept frozen in similar conditions. These samples will be used in the placebo arm for autologous vaginal fluid transplantation. Before transplantation, patients will be treated with intravaginal antibiotic. Following Placebo, patients will be evaluated every 14 days for the first 2 months, then every month for additional 2-4 months. After 4-6 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.	Biological: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical parameters- patient's complains	Number of participants reporting disappearance of discharge and odor	12 months
Laboratory parameters- Amsel criteria	Presence or absence of each Amsel criteria (discharge, pH>4.5, positive whiff test and clue cells on microscopy)/	12 months
Vaginal fluid microscopy	Presence of Lactobacillus-dominant microbiome on microscopy	12 months
Microbiome composition	Characterization of the vaginal microbial community using shotgun analysis and16S rRNA sequencing	12 months

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Collaborators: Weizmann Institute of Science
• Investigators: Principal Investigator: Ahinoam Lev-Sagie, Hadassah Medical Organization

Publications and helpful links

General Publications

• Lev-Sagie A, Goldman-Wohl D, Cohen Y, Dori-Bachash M, Leshem A, Mor U, Strahilevitz J, Moses AE, Shapiro H, Yagel S, Elinav E. Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nat Med. 2019 Oct;25(10):1500-1504. doi: 10.1038/s41591-019-0600-6. Epub 2019 Oct 7.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: August 15, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vaginitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Vaginal Diseases; Vaginosis, Bacterial
• Other Study ID Numbers: HMO-19-691

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No