MOTIF@FRESH: Modifying Organisms Transvaginally in Females @ FRESH

NCT07566754 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026P000260
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The MOTIF@ FRESH trial will assess the safety and efficacy of "vaginal microbiome transplantation" (VMT). Healthy females will be enrolled to donate vaginal fluid which will be processed and transplanted in females with a history of recurrent bacterial vaginosis (BV), treated with antibiotics.

Conditions

Recurrent Bacterial Vaginosis (BV)

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of VMT

  The primary outcome of the study is to evaluate if VMT increases the proportion of women with a Lactobacillus crispatus-dominant microbiota at any time 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.

  for 23 weeks after intervention

Secondary Outcomes (2)

• Determine whether VMT will result in a durable change in vaginal microbiota

  2, 12, and 24 weeks after intervention

• Characterize the host clinical and subclinical mucosal inflammatory response before and after VMT

  24 weeks after intervention

Study Arms (2)

Recipient: Placebo

PLACEBO COMPARATOR

Women in this group will be randomized to receive three doses of sterile saline solution

Drug: oral metronidazole; Other: Sterile saline solution

Recipient: Vaginal Microbiome Transplantation (VMT)

ACTIVE COMPARATOR

Women in this group will be randomized to receive three doses of VMT

Biological: Vaginal Microbiome Transplantation (VMT); Drug: oral metronidazole

Interventions

Vaginal Microbiome Transplantation (VMT) BIOLOGICAL

Vaginal fluid from healthy donors

Recipient: Vaginal Microbiome Transplantation (VMT)

oral metronidazole DRUG

Metronidazole 400 mg PO every 12 hours for 7 days is the concomitant medication. This antibiotic course is the standard Bacterial Vaginosis (BV) treatment which effectively eliminates microbes associated with BV for a limited time.

Recipient: Placebo; Recipient: Vaginal Microbiome Transplantation (VMT)

Sterile saline solution OTHER

1mL of sterile saline solution

Recipient: Placebo

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal females between 18 to 25 years of age who are enrolled in the FRESH study
• Nugent score ≥ 4
• 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.

You may not qualify if:

• History of clinically significant vaginal, cervical, or uterine disease including but not limited to cancer of the female reproductive tract, prior hysterectomy, high grade cervical dysplasia (CIN III), or diagnosed with cervicovaginal infection (with the exception of bacterial vaginosis or yeast) within the 30 days prior to the procedure
• Allergy to metronidazole
• Use of investigational therapies or investigational vaccines within 90 days prior to study screening
• Has not received the HPV vaccine and is not willing to be vaccinated
• Metabolic syndrome, e.g. diabetes, pre-diabetes, glucose intolerance
• Use of any immunomodulatory agents within 30 days prior to study enrollment
• Participants taking any of the following medications: systemic steroids (inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons, or systemic chemotherapy
• History of coronary artery disease, myocardial infarction, COPD, chronic renal failure, decompensated cirrhosis, or any other condition that in the opinion of the investigator will compromise ability to participate in the study
• Pap smear result of LSIL, HSIL, AGUS
• Insertion of levonorgestrel-containing IUD within 90 days prior to study enrollment
• Either breastfeeding, pregnant, or trying to conceive within 24 weeks prior to study enrollment; or becomes pregnant during study period
• Use of probiotics and prebiotics (supplements and products, oral or vaginal) within 30 days of the study
• \- NOTE: Oral yogurt with live cultures and fermented foods are allowed.
• Routine use of oral antibiotics i.e., daily use for acne, Hiradenitis suppurativa, or regular use for post-coital urinary tract infection prophylaxis within the past 30 days
• Taken non-metronidazole antibiotics in last 30 days

Sponsors & Collaborators

• Douglas Kwon: lead
• Bill and Melinda Gates Foundation: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (1)

FRESH Clinic

Durban, South Africa

Location

MeSH Terms

Conditions

Vaginosis, Bacterial

Interventions

Metronidazole

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)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Douglas S Kwon, MD, PhD

  Ragon Institute of MGB, MIT, and Harvard

  PRINCIPAL INVESTIGATOR

• Caroline Mitchell, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Krista Dong, MD

  Ragon Institute of MGB, MIT, and Harvard

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah M Eisa, MPH

CONTACT

551-689-4016; seisa@mgh.harvard.edu

Eyerusalem T Alemu, BA

CONTACT

619-522-4661; ealemu@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants will be randomized 2:1 to VMT vs. placebo

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 5, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

ZA (1)