Bacterial Vaginosis
Conditions
Interventions
Metronidazole and Placebo
Metronidazole and Vaginal Micribiome Transplantation VMT
Vaginal Fluid Donations
Sponsors
Ragon Institute of MGH MIT and Harvard
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Donors inclusion criteria: • Premenopausal females between 18 to 25 years of age who are enrolled in the FRESH study • Negative urine pregnancy test at screening and prior to first donation • Sexually active, but willing to abstain from sex (or use a condom) at least 48 hours before screening and donations. • Able to pass a screening questionnaire based on the South African National Blood Services (SANBS) blood donor screening questionnaire for exposure to infectious agents • Physical and pelvic exams show no physical evidence for risk of sexually transmitted diseases, drug use, recent tattoos and piercings, and opportunistic infections • No significant medical conditions, such as experiencing recurring bothersome vaginal discharge, that would impact the outcome of the proposed study (investigator discretion) • General laboratory screening tests within range (FBC with differential, HbA1c, basic chemistry panel, and liver function tests) • Nugent score < 4 • Vaginal pH < 5 • Ability and willingness to give written informed consent to participate in the study as described, allow us to store and share their samples, and conduct genetic tests (three separate informed consent forms) • Ability and willingness to comply with study requirements Recipients: • Premenopausal females between 18 to 25 years of age who are enrolled in the FRESH study • Nugent score of 4 or higher • Confirmation of use of effective contraceptive method by all study recipient participants (referred to as recipients) of child-bearing potential, which includes use of at least one of the following: - Hormonal method, such as birth control pills, patches, injections, vaginal rings, or implants - Barrier method, such as a condom or diaphragm used with a spermicide (a foam, cream, or gel that kills sperm) - Intrauterine device (IUD) – non-levonorgestrel containing • Ability and willingness to give written informed consent.
Exclusion criteria
Exclusion criteria: Donors: • Any current malignancy • Screens positive for risky alcohol consumption • History of sexually transmitted infections in the past 12 months • History of positive result(s) for high-risk HPV within the past year without appropriate follow-up • The most recent pap/HPV test is abnormal and without appropriate follow-up • History of endometriosis with pain • Current use of probiotics and prebiotics (supplements and products, oral or vaginal) • NOTE: Oral yogurt with live cultures and fermented foods are allowed • Use of oral, IV, or vaginal antibiotics within the past 90 days • Current or recent use (within the past 90 days) of major oral or IV immunosuppressive medications, e.g., calcineurin inhibitors, exogenous glucocorticoids, biologic agents, etc. • Use of systemic anti-neoplastic agents • Metabolic syndrome, e.g. diabetes, pre-diabetes, glucose intolerance • Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD) • Neurological, neurodevelopmental disorder e.g. Parkinson’s disease, autism, etc. • Systemic autoimmunity, e.g., multiple sclerosis, psoriasis, vasculitis, connective tissue disease, any rheumatological or inflammatory condition • Chronic pain syndromes, e.g., chronic fatigue syndrome, fibromyalgia • Confirmed HIV infection • Confirmed Hepatitis B or C infection • Prior or active HSV1 or HSV2 infection (painful blistering genital lesions) • Non-prescribed injection drug use in the preceding 5 years, including intravenous, intramuscular, and subcutaneous injections • Having sex in the preceding 12 months with any person meeting any of the criteria described immediately above (someone who uses non-medical injected drugs or has sex in exchange for money or drugs), or with any person having HIV infection including a positive or reactive test to HIV, hepatitis B infection, or clinically active (symptomatic) hepatitis C infection • (see attachments for remaining exclusion criteria of donor procotol, and those of recipient protocol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate if vaginal microbial transplant increases the proportion of women with a Lactobacillus crispatus-dominant microbiota at anytime within the 4 weeks after the first dose as measured by sequencing of the microbial community where Lactobacillus crispatus make up > 50% of detected microbes. | — |
Secondary
| Measure | Time frame |
|---|---|
| Measure Lactobacillus crispatus dominance across follow-up weeks. We will also assess safety, toxicity, and tolerability of VMT. This will be measured by a) follow up pelvic assessments to assess for rash, irritation or infection, b) patient symptom questionnaires to assess self-reported symptoms of vulvovaginal discomfort, and c) adverse event reporting form. Additional secondary, exploratory analyses to help evaluate mechanisms for increased Lactobacillus prevalence or lack thereof include proportions of individual Lactobacillus species (e.g., L. crispatus, L. iners, L. jensenii, L. gasseri), vaginal microbial community type, microbial community diversity measures, individual taxa associated with treatment group, and host mucosal inflammatory immune response. (e.g., vaginal concentration of IL1beta, IL1alpha, IL1RA, IL6, IL8, TNFa, IFNg) | — |
Countries
South Africa
Contacts
Public ContactSarah Eisa
Program Manager of Programs in South Africa in the Kwon Lab at the Ragon Institute of MGH MIT and Harvard
Outcome results
None listed