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Not yet recruitingNCT07566754MOTIF@FRESHUpdated May 18, 2026

MOTIF@FRESH: Modifying Organisms Transvaginally in Females @ FRESH

A Phase 2 interventional study of Vaginal Microbiome Transplantation (VMT) and oral metronidazole in Recurrent Bacterial Vaginosis (BV), sponsored by Douglas Kwon. Not yet recruiting at 1 site in South Africa. Open to female participants aged 18 Years to 25 Years. Per ClinicalTrials.gov, last updated 2026-05-18.

Sponsored by Douglas Kwon · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
75
Allocation
Randomized
Ages
18 Years to 25 Years
Sex
Female
01

Study 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.

Read the detailed description

The proposed randomized, double-blinded, placebo-controlled trial is to evaluate the safety of vaginal microbiota transplantation (VMT) in women with recurrent bacterial vaginosis (BV). The study is based in South Africa, at the FRESH (Females Rising through Education, Support, and Health) Clinical Research Site (CRS) located in the Umlazi Township of Durban. The aim of the trial is to assess the ability of antibiotic treatment plus VMT to establish a Lactobacillus-dominant vaginal community. The underlying hypothesis is that the VMT will lead to less inflammation and higher prevalence of vaginal Lactobacillus compared to antibiotics alone. The transplant material will be vaginal fluid collected from healthy donors (also known as Donors) using a disposable menstrual cup.

Donors are defined as participants with Nugent scores \<4. Over a 16-week period, donors will provide vaginal fluid via softcups (referred to as "donations"). All donations will undergo extensive testing for sexually transmitted infections (STIs) and other infections. Donations that test negative for specified infections will be processed to generate vaginal microbial transplantation (VMT) doses for recipients.

Recipients are defined as participants with Nugent scores ≥4. Because the HPV vaccine is not routinely administered in South Africa, all recipients without documented proof of prior HPV vaccination will receive the HPV vaccine at least 30 days prior to the intervention. The intervention includes the standard of care for bacterial vaginosis in both the U.S. and South Africa: oral metronidazole (MTZ), administered twice daily for seven days. Following completion of the MTZ course, recipients will receive three VMT doses administered over approximately 1.5 weeks. Recipients will be randomized in a 2:1 ratio to receive either VMT or placebo and will be followed for six months post-intervention.

02

Conditions studied

  • Recurrent Bacterial Vaginosis (BV)

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03

Who can participate

Ages eligible
18 Years to 25 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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
  • Taken metronidazole within the last 2 weeks
  • BMI > 40
  • Positive for any of the STIs listed below or on treatment for any of them.

    • Neisseria gonorrhoeae
    • Chlamydia trachomatis
    • HIV
    • Trichomonas vaginalis
    • Syphilis
    • Mycoplasma genitalium
  • Currently employed at, or professionally affiliated with the FRESH clinical research site, UKZN's HIV Pathogenesis Program (HPP), or the Ragon Institute of Mass General Brigham, MIT and Harvard (referred to as "the Ragon/MGH" in this document).
  • Screens positive for TB by symptomatic questionnaire
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
75 participants (estimated)

Study arms

  • Placebo comparator
    Recipient: Placebo

    Women in this group will be randomized to receive three doses of sterile saline solution after completing a full course of MTZ

    Drug: oral metronidazole · Other: Sterile saline solution

  • Active comparator
    Recipient: Vaginal Microbiome Transplantation (VMT)

    Women in this group will be randomized to receive three doses of VMT after completing a full course of MTZ

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

Interventions

  • BiologicalVaginal Microbiome Transplantation (VMT)

    Vaginal fluid from healthy donors

  • Drugoral metronidazole

    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.

  • OtherSterile saline solution

    1mL of sterile saline solution

05

What researchers measure

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.

    Time frame: for 23 weeks after intervention

Secondary outcomes

  1. Determine whether VMT will result in a durable change in vaginal microbiota

    Secondary outcome will measure Lactobacillus crispatus dominance across follow-up weeks. The hypothesis is that antibiotic plus VMT therapy will increase the proportion of women with a Lactobacillus crispatus-dominant microbiota from 5-10% to 50-60%. The safety, toxicity, and tolerability of VMT will also be assessed via a) follow up pelvic assessments to assess for rash, irritation or infection calls, b) patient symptom questionnaires to assess self-reported symptoms of vulvovaginal discomfort, and c) adverse event reporting.

    Time frame: 2, 12, and 24 weeks after intervention

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

    Additional secondary, exploratory analyses will be done to evaluate mechanisms for increased Lactobacillus prevalence, or lack thereof. This will include measuring proportions of individual Lactobacillus species (e.g., L. crispatus, L. iners, L. jensenii, L. gasseri), assessing 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)

    Time frame: 24 weeks after intervention

06

Study locations

1 site
  • FRESH Clinic
    Durban, South Africa
    • Thembelihle Dlamini · Contact · lihle.fresh@ragoninsa.org · +27 73 318 9320
    • Sooseela V Pillay · Contact · vanessa.fresh@ragoninsa.org · +27 31- 9060394
    • Rosie Mngqbisa, MBChB, MPH · Principal investigator
    • Funidiswe Chonco, MD · Sub investigator
    • Siphesihle R Ngcobo, MD · Sub investigator
    • Thumbi Ndung'u, PhD · Principal investigator
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07566754
Lead sponsor
Douglas Kwon
Collaborators
Massachusetts General Hospital, Bill and Melinda Gates Foundation
Responsible party
Douglas Kwon (Principal Investigator, Massachusetts General Hospital) — Sponsor-investigator
First posted
May 5, 2026
Start date
Sep 2026 (estimated)
Primary completion
May 2027 (estimated)
Completion
Feb 2028 (estimated)
Last update
May 18, 2026

Study contacts

Sarah M Eisa, MPH
Contact
seisa@mgh.harvard.edu
551-689-4016
Eyerusalem T Alemu, BA
Contact
ealemu@mgh.harvard.edu
619-522-4661
Douglas S Kwon, MD, PhD
principal investigator · Ragon Institute of MGB, MIT, and Harvard
Caroline Mitchell, MD, MPH
principal investigator · Massachusetts General Hospital
Krista Dong, MD
principal investigator · Ragon Institute of MGB, MIT, and Harvard

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is not yet recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

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