Vaginal Microbiome Transplantation for Recurrent Bacterial Vaginosis

NCT04517487 | Recruiting

• 1 other identifier: HMO-19-691
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

Conditions

Bacterial Vaginoses

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

VMT recipients

ACTIVE COMPARATOR

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

Vaginal Microbiome Transplantation (VMT) BIOLOGICAL

Healthy donors vaginal fluid is introduced into recipients' vagina to replace their indigenous disease-associated microbiome

VMT recipients

Placebo BIOLOGICAL

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Pregnancy or a planned pregnancy in the upcoming year
• Infection with HIV.
• Immunodeficiency status.

Sponsors & Collaborators

• Hadassah Medical Organization: lead
• Weizmann Institute of Science: collaborator

Study Sites (1)

Hadassah Medical Center

Jerusalem, Jerusalem, 9765422, Israel

RECRUITING

Related Publications (1)

• 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.

  PMID: 31591599 BACKGROUND

MeSH Terms

Conditions

Vaginosis, Bacterial

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Ahinoam Lev-Sagie

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahinoam Lev-Sagie

CONTACT

+972544327178; levsagie@netvision.net.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: August 15, 2020
• First Posted: August 18, 2020
• Study Start: August 20, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)