Safety and Efficacy of Vaginal Microbiota Transplant (VMT) in Women With Bacterial Vaginosis (BV)

NCT03769688 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: NA_00090758
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The composition of a woman's vaginal microbiota has a significant impact on her reproductive tract health and general quality of life. Approximately one-third of all women currently have bacterial vaginosis (BV), a polymicrobial condition in which the vaginal microbiota is not dominated by Lactobacillus species, leading to increased risk of various reproductive tract maladies and negative impact on well-being. It has been suggested by epidemiological studies that vaginal microbiota are readily transferable from one woman to another. Here, investigators aim to explore the hypothesis that vaginal microbiota can be engrafted from one woman to another in a controlled clinical setting by using cervicovaginal secretions (CVS), a process referred to as vaginal microbiota transplant (VMT).

Conditions

Bacterial Vaginosis

Keywords

bacterial vaginosis; cervicovaginal secretions; vaginal microbiota

Outcome Measures

Primary Outcomes (1)

• Bacteria engraftment as assessed by ribosomal (rDNA) gene sequencing

  Detection of Donor vaginal Lactobacillus in Recipient by 16S rDNA gene sequencing (\~1% or greater relative abundance by read count)

  28 days

Secondary Outcomes (4)

• Bacteria engraftment as assessed by rDNA gene sequencing

  10 days

• Bacterial communities as assessed by rDNA gene sequencing

  At screening , and then follow-up (~7 months)

• Bacterial vaginosis recurrence as assessed by Amsel's criteria

  Up to 6 months after VMT procedure

• Bacterial vaginosis recurrence as assessed by Nugent score

  Up to 6 months after VMT procedure

Study Arms (2)

Cervicovaginal secretions

EXPERIMENTAL

Participants will receive standard of care antibiotics (vaginal Metronidazole gel). After standard antibiotic treatment, participants will receive a single intravaginal dose of cervicovaginal secretions (10 mg in 1 ml total volume, 0.9 ml normal saline).

Drug: Cervicovaginal secretions; Drug: Metronidazole gel; Diagnostic Test: Screening tests; Behavioral: Activities restriction

Saline placebo

PLACEBO COMPARATOR

Participants will receive standard of care antibiotics (vaginal Metronidazole gel). After standard antibiotic treatment, participants will receive a single intravaginal dose of sterile saline placebo (1 ml total volume).

Drug: Metronidazole gel; Diagnostic Test: Screening tests; Behavioral: Activities restriction; Other: Sterile Saline placebo

Interventions

Cervicovaginal secretions DRUG

Same as arm descriptions

Cervicovaginal secretions

Metronidazole gel DRUG

5 day course of vaginal MetroGel will be used prior to VMT intervention.

Cervicovaginal secretions; Saline placebo

Screening tests DIAGNOSTIC_TEST

Diagnostic testing for a broad range of infectious pathogens in blood, vaginal swab, and urine samples, for general immunocompetence, and for potential pregnancy.

Cervicovaginal secretions; Saline placebo

Activities restriction BEHAVIORAL

Required abstinence from sexual intercourse, usage of insertive vaginal feminine products (i.e. Tampons, menstrual cups, sex toys), other vaginal products (cleansing products, spermicides, lubricants, hygiene powders and sprays), and avoidance of behaviors including taking baths, going swimming, sitting in hot tub, or wearing thong underwear. Sanitary napkins are acceptable.

Cervicovaginal secretions; Saline placebo

Sterile Saline placebo OTHER

This will be administered as a placebo in place of cervicovaginal secretions

Saline placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Capable of reading and writing English and voluntarily provide written informed consent to participate in the study and comply with all study procedures.
• Generally healthy, pre-menopausal women age 18-45 years old.
• Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of long-acting progestin or continuous use of oral contraceptives.
• Free of vaginal symptoms, such as odor, discharge, or itching.
• Willing to be asked questions about personal medical, sexual, and behavioral history.
• Willing to self-collect cervicovaginal secretions and vaginal swab samples.
• Agree to abstain from using insertive vaginal feminine products (i.e. Tampons, menstrual cups, sex toys), other vaginal products (cleansing products, spermicides, lubricants, hygiene powders and sprays), vaginal and anal intercourse, taking baths, going swimming, sitting in hot tub, or wearing thong underwear during the entire sample donation period (from screening to the final donation). Sanitary napkins are acceptable.
• Capable of reading and writing English and voluntarily provide written informed consent to participate in the study and comply with all study procedures.
• Generally healthy, pre-menopausal women age 18-45 years old.
• Experiences recurrent bacterial vaginosis (BV) (at least 3 diagnoses in their lifetime), and has received treatment for BV on at least 1 prior occasion in the past 5 years.
• Currently needing treatment for vaginal symptoms clinically diagnosed as BV (\>= 3 Amsel criteria and confirmed in the laboratory by Nugent score \>= 4) and suitable for 0.75% metronidazole vaginal antibiotic treatment.
• Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of long-acting progestin or continuous use of oral contraceptives.
• Women who are not sterilized or who are not using an Intra-uterine Device (IUD) or form of hormonal contraception must agree to barrier contraception (i.e. Condoms, diaphragm) for heterosexual intercourse during the study. Counseling will be provided for use of barrier contraception without the use of adjunctive spermicide or lubricant.
• Willing to be asked questions about personal medical, sexual, and behavioral history.
• Willing to self-collect cervicovaginal secretions and vaginal swab samples.

You may not qualify if:

• Any history of bacterial vaginosis, recurrent yeast infection, trichomoniasis, syphilis, human papilloma virus (HPV) including genital warts, high grade pap smear, herpes, pelvic inflammatory disease, recurrent urinary tract infection, mycoplasma.
• Testing positive for HIV, Hepatitis A/B/C, syphilis, Human T-lymphotrophic Virus (HTLV)-I/II, WNV, Epstein-Barr Virus (EBV), rubella, toxoplasma gondii, Herpes Simplex Virus (HSV)-1/2, yeast or bacteria that are considered pathogenic/abnormal and/or show antibiotic resistance, chlamydia, gonorrhea, mycoplasma genitalium, trichomonas vaginalis, HPV.
• Cervicovaginal secretions (CVS) not dominated by one of the common vaginal lactobacillus species, as determined by qPCR.
• Currently pregnant or breastfeeding.
• History of gonorrhea or chlamydia within 12 months prior to screening.
• Travel or sexual partner travel to regions or countries where Ebola or Zika outbreaks occurred in the past 12 months.
• Any other medical, travel, or behavioral history that deems donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps) ineligible.
• HIV/AIDS or other immunodeficiency, or testing out of the range of normal clinical parameters for general measures of immunocompetence.
• Hysterectomy.
• Use of vaginal ring (e.g., NuvaRing) within 3 days of screening or during the course of the study.
• Investigational drug use within 30 days or 10 half-lives of the drug, whichever is longer, of enrollment visit, or planned participation in an investigational drug study while participating in this study.
• IUD insertion or removal, cervical cryotherapy, or cervical laser treatment within 2 months prior to screening.
• Any condition requiring regular periodic use of systemic antibiotics during the study.
• New use of long-acting hormonal treatments. Participant may be enrolled if stable (\>3 months) or existing therapy as determined by the investigator.
• Any social, medical, or psychiatric condition, including history of drug or alcohol abuse that in the opinion of the investigator would make it unlikely for the participant to comply with the study or would complicate interpretation of data from her participation.

Sponsors & Collaborators

• Johns Hopkins University: lead

MeSH Terms

Conditions

Vaginosis, Bacterial

Interventions

Early Detection of Cancer

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

Intervention Hierarchy (Ancestors)

Early Diagnosis; Diagnosis

Study Officials

• Laura Ensign, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 7, 2018
• Study Start: March 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 3, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share