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

NCT ID: NCT03769688

Last Updated: 2021-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-31

Study Completion Date

2023-12-31

Brief Summary

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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).

Detailed Description

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Conditions

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Bacterial Vaginosis

Keywords

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bacterial vaginosis cervicovaginal secretions vaginal microbiota

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Cervicovaginal secretions

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).

Group Type EXPERIMENTAL

Cervicovaginal secretions

Intervention Type DRUG

Same as arm descriptions

Metronidazole gel

Intervention Type DRUG

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

Screening tests

Intervention Type 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.

Activities restriction

Intervention Type 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.

Saline placebo

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).

Group Type PLACEBO_COMPARATOR

Metronidazole gel

Intervention Type DRUG

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

Screening tests

Intervention Type 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.

Activities restriction

Intervention Type 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.

Sterile Saline placebo

Intervention Type OTHER

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

Interventions

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Cervicovaginal secretions

Same as arm descriptions

Intervention Type DRUG

Metronidazole gel

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

Intervention Type DRUG

Screening tests

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

Intervention Type DIAGNOSTIC_TEST

Activities restriction

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.

Intervention Type BEHAVIORAL

Sterile Saline placebo

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Capable of reading and writing English and voluntarily provide written informed consent to participate in the study and comply with all study procedures.
2. Generally healthy, pre-menopausal women age 18-45 years old.
3. Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of long-acting progestin or continuous use of oral contraceptives.
4. Free of vaginal symptoms, such as odor, discharge, or itching.
5. Willing to be asked questions about personal medical, sexual, and behavioral history.
6. Willing to self-collect cervicovaginal secretions and vaginal swab samples.
7. 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.


1. Capable of reading and writing English and voluntarily provide written informed consent to participate in the study and comply with all study procedures.
2. Generally healthy, pre-menopausal women age 18-45 years old.
3. 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.
4. 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.
5. Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of long-acting progestin or continuous use of oral contraceptives.
6. 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.
7. Willing to be asked questions about personal medical, sexual, and behavioral history.
8. Willing to self-collect cervicovaginal secretions and vaginal swab samples.
9. Willing to undergo VMT procedure.
10. Agree to abstain from vaginal intercourse, unless using a condom, for at least the 28 days after the VMT procedure. Condoms will be provided.
11. Agree to avoid taking baths, swimming, sitting in a hot tub, or wearing thong underwear for at least the 28 days after the VMT procedure.
12. Agree to abstain from using insertive vaginal feminine products (i.e. Tampons, menstrual cups, sex toys), vaginal cleansing products, spermicides, lubricants, or other vaginal products not approved by the study investigators after the VMT procedure through visit 8 (\~6 months). Sanitary napkins are acceptable.

Exclusion Criteria

1. 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.
2. 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.
3. Cervicovaginal secretions (CVS) not dominated by one of the common vaginal lactobacillus species, as determined by qPCR.
4. Currently pregnant or breastfeeding.
5. History of gonorrhea or chlamydia within 12 months prior to screening.
6. Travel or sexual partner travel to regions or countries where Ebola or Zika outbreaks occurred in the past 12 months.
7. Any other medical, travel, or behavioral history that deems donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps) ineligible.
8. HIV/AIDS or other immunodeficiency, or testing out of the range of normal clinical parameters for general measures of immunocompetence.
9. Hysterectomy.
10. Use of vaginal ring (e.g., NuvaRing) within 3 days of screening or during the course of the study.
11. 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.
12. IUD insertion or removal, cervical cryotherapy, or cervical laser treatment within 2 months prior to screening.
13. Any condition requiring regular periodic use of systemic antibiotics during the study.
14. New use of long-acting hormonal treatments. Participant may be enrolled if stable (\>3 months) or existing therapy as determined by the investigator.
15. 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.
16. Menopause defined as more than 12 consecutive months of amenorrhea without another known cause.
17. Irregular menstrual cycles that preclude scheduling appointments to avoid menstruation.
18. Donors will be screened for cytomegalovirus (CMV), Rubella, and Varicella Zoster Virus (VZV) IgG, which will not be a criterion for exclusion, but samples from CMV positive and/or Rubella positive and/or VZV positive Donors will only be matched with CMV positive and/or Rubella and/or VZV positive Recipients.
19. Abnormal finding on exam, which, in the opinion of the investigator, precludes participation.
20. Sexual history or current sexual behavior, or having sexual partners that engage in such behaviors, which introduces increased risk of sexually transmitted infections or exposure to pathogenic organisms.
21. Medication use, recent vaccinations, sources of income, or other behaviors, which in the opinion of the investigator, precludes participation.


1. Current pregnancy, within 2 months of pregnancy, planning to become pregnant within the next 6 months, and/or currently breastfeeding.
2. HIV/AIDS or other immunodeficiency.
3. Testing positive for HIV, HTLV-I/II, yeast infection, chlamydia, gonorrhea, mycoplasma genitalium, trichomonas, antibiotic-resistant bacteria in culture, or human Chorionic Gonadotrophin (hCG) (urine).
4. Hysterectomy.
5. High grade pap smear within the past year.
6. Use of vaginal ring (e.g., NuvaRing) during the course of the study.
7. 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.
8. IUD insertion or removal, cervical cryotherapy, or cervical laser treatment within 2 months prior to screening.
9. Any condition requiring regular periodic use of systemic antibiotics during the study.
10. New use of long-acting hormonal treatments. Participant may be enrolled if stable (\>3 months) or existing therapy as determined by the investigator.
11. 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.
12. Menopause defined as more than 12 consecutive months of amenorrhea without another known cause.
13. Recipients will be screened for cytomegalovirus (CMV), Rubella, and Varicella Zoster Virus (VZV) IgG, which will not be a criterion for exclusion, but samples from CMV positive and/or Rubella positive and/or VZV positive Donors will only be matched with CMV positive and/or Rubella and/or VZV positive Recipients.
14. Abnormal finding on exam, which, in the opinion of the investigator, precludes participation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laura Ensign, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Other Identifiers

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NA_00090758

Identifier Type: -

Identifier Source: org_study_id