Vaginal Microbiota Transplant for Bacterial Vaginosis

(MOTIF Trial)

Overseen By Doug Kwon, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Douglas Kwon

Must not be taking: Immunomodulators, Systemic steroids

Disqualifiers: Cancer, Hysterectomy, Pregnancy, others

Compensation: Varies

Number of Visits: 10

Duration: 1 week

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is studying a new treatment for women with frequent episodes of bacterial vaginosis (BV), a common vaginal infection. The researchers are comparing a vaginal microbiota transplant (using healthy donor vaginal fluid) to a saline placebo to determine if it can restore a healthy bacterial balance. Women who have experienced BV three or more times in the past year might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group. Participants have the opportunity to contribute to groundbreaking advancements in BV treatment.

Do I have to stop taking my current medications for this trial?

You may need to stop certain medications. You can't use immunomodulatory agents, probiotics, prebiotics, or routine oral antibiotics within 30 days before the study. Also, you can't have taken non-metronidazole antibiotics in the last 30 days.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vaginal microbiota transplant (VMT) is generally safe. Studies have found that VMT is well-tolerated for treating bacterial vaginosis and other vaginal infections. No major reports of serious side effects have emerged, making it a promising option for people with recurring issues. This suggests that VMT is a safe treatment, with experts continuing to monitor for any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bacterial vaginosis?

Most treatments for bacterial vaginosis focus on antibiotics, which aim to kill off harmful bacteria but can also disrupt the overall balance of the vaginal microbiome. Unlike these standard treatments, the vaginal microbiota transplant introduces healthy bacteria from a donor to restore a balanced microbial environment. This method harnesses the body's natural microbiome to fight off infection, potentially offering longer-lasting results and reducing the recurrence of symptoms. Researchers are excited about this approach because it targets the root cause of bacterial vaginosis by re-establishing a healthy vaginal flora, rather than just eliminating harmful bacteria.

What evidence suggests that this trial's treatments could be effective for bacterial vaginosis?

This trial will compare the effectiveness of a vaginal microbiota transplant (VMT) with a saline placebo for treating bacterial vaginosis (BV). Studies have shown that VMT can effectively treat BV by restoring a healthy balance of bacteria, particularly by increasing Lactobacillus, the beneficial bacteria. Research indicates that VMT can improve the vaginal environment for an extended period without antibiotics. Initial findings suggest that this method may offer a promising option for women with recurring BV, providing effective, long-term management of the condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Doug Kwon, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 18-50 with recurrent bacterial vaginosis, who have had at least three episodes in the past year. Participants must not be pregnant or breastfeeding, should agree to use effective contraception if sexually active, and cannot have a BMI over 40 or serious health conditions like heart disease.

Inclusion Criteria

If participating in sexual activity that could lead to pregnancy, study participants must agree to use an effective contraceptive while actively participating in the protocol. At least one of the following methods MUST be used:

I am a woman aged 18-50 and have not gone through menopause.

I have had bacterial vaginosis 3 or more times in the last year.

Exclusion Criteria

I have had a levonorgestrel IUD inserted within the last 3 months.

I haven't used probiotics or prebiotics in the last 30 days, except for oral yogurt.

Either breastfeeding or pregnant within 24 weeks prior to study entry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person), 1 phone call

Baseline

Baseline assessments and randomization into study groups

1 week

1 visit (in-person)

Treatment

Administration of vaginal microbiota transplant or placebo

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

6 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Vaginal Microbiota Transplant

Trial Overview

The study is testing whether a vaginal microbiome transplant can establish a healthy Lactobacillus-dominated microbial community compared to a saline placebo. It's for those who haven't responded well to traditional treatments and involves random assignment into treatment groups.

How Is the Trial Designed?

Group I: Vaginal microbiome transplant Active Control 2 Interventions

Women in this group will be randomized to receive two doses of vaginal fluid from a healthy donor

Group II: Saline placebo Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Douglas Kwon

Lead Sponsor

Trials

1

Recruited

60+

Published Research Related to This Trial

Vaginal microbiota transplantation (VMT) is being explored as a promising new treatment, similar to fecal microbiota transplantation (FMT), particularly for preventing the recurrence of bacterial vaginosis (BV).

The article highlights the medical, regulatory, and ethical challenges that need to be addressed as VMT moves towards clinical trials, emphasizing the need for careful research design and regulatory considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal Microbiota Transplantation: The Next Frontier. DeLong, K., Zulfiqar, F., Hoffmann, DE., et al.[2020]

In a small exploratory study involving five women with recurrent bacterial vaginosis, vaginal microbiome transplantation (VMT) led to full long-term remission in four patients, with follow-up lasting between 5 to 21 months.

No adverse effects were reported from the procedure, suggesting that VMT is a safe therapeutic alternative, although some patients required multiple treatments for sustained results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Lev-Sagie, A., Goldman-Wohl, D., Cohen, Y., et al.[2021]

Conventional antibiotic treatments for bacterial vaginosis (BV) often worsen microbial imbalances and lead to drug resistance, resulting in low cure rates and high recurrence rates.

Vaginal microbiota transplantation (VMT) offers a promising alternative by transferring healthy vaginal microbiota to patients, aiming to restore vaginal health more effectively than traditional antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review]. Wei, K., Chen, T.[2021]

Fecal microbiota transplant (FMT) has shown success in treating recurrent Clostridioides difficile infections, leading to interest in vaginal microbiota transplant (VMT) as a potential therapy for conditions related to microbial imbalance, particularly bacterial vaginosis (BV).

A pilot study involving 20 women established a universal donor screening approach to identify optimal donors with healthy vaginal microbiota, which is crucial for ensuring safety and efficacy in future VMT clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conceptual Design of a Universal Donor Screening Approach for Vaginal Microbiota Transplant. DeLong, K., Bensouda, S., Zulfiqar, F., et al.[2020]

Vaginal microbiota transplantation (VMT) is proposed as a promising alternative treatment for bacterial vaginosis (BV), which often recurs after antibiotic therapy, but it requires strict safety protocols due to potential risks.

The study established that Lactobacillus bacteria can remain viable for over six months when stored at -80 °C, and introduced a rapid screening method using species-specific quantitative PCR to identify healthy donors with optimal vaginal microbiomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening and characterization of vaginal fluid donations for vaginal microbiota transplantation. Yockey, LJ., Hussain, FA., Bergerat, A., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10995359/

Vaginal microbiota transplantation is a truly opulent and ...

Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04046900?term=LACTOBACILLUS%20CRISPATUS&rank=9

NCT04046900 | Vaginal Microbiota Transplant

The investigators propose a randomized, double-blind, placebo-controlled trial to evaluate the safety of vaginal microbiota transplant (VMT) in women with ...

3.

nature.com

nature.com/articles/s41598-022-22873-y

Screening and characterization of vaginal fluid donations ...

VMT is a promising strategy to promote a Lactobacillus-dominant vaginal microbiota in people with recurrent BV. Studies of VMT will also provide ...

4.

medrxiv.org

medrxiv.org/content/10.1101/2024.06.25.24309408v1.full-text

Antibiotic-free vaginal microbiota transplantation (VMT) ...

Our study shows that VMT has great potential as the first therapeutic intervention that provides effective and long-term vaginal microbiota ...

5.

academic.oup.com

academic.oup.com/humrep/article/39/Supplement_1/deae108.327/7703658

O-280 Vaginal microbiota transplant (VMT) without antibiotic ...

There is a clear need for alternatives and recently it was shown that VMT following antibiotic treatment resulted in long-lasting improvements ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40909844/

Donation strain engraftment demonstrates feasibility of ...

Although bacterial vaginosis (BV) affects 30% of women worldwide and is associated with adverse health outcomes, current standard-of-care ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04517487

Vaginal Microbiome Transplantation for Recurrent ...

Vaginal Microbiome Transplantation (VMT) may be beneficial in treating the most severe cases of recurrent and antibiotics-nonresponsive cases of BV.