Live Biotherapeutic Product for Bacterial Vaginosis

(VIBRANT Trial)

No longer recruiting at 1 trial location

Overseen By Doug Kwon, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must be taking: Oral contraceptives

Must not be taking: Systemic steroids, Interleukins

Disqualifiers: Vaginal disease, Cervicovaginal infection, Syphilis, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new treatment can safely assist individuals with bacterial vaginosis (BV) by using a live biotherapeutic product (a type of probiotic) to restore healthy bacteria in the vagina after antibiotic treatment. Researchers will test different versions of this probiotic, containing multiple strains of L. crispatus, to see if they can successfully establish and thrive in the vagina. Individuals diagnosed with BV and currently undergoing antibiotic treatment, such as Metronidazole Oral, might be suitable for this trial. Participants will engage in daily home activities like collecting swabs and maintaining a short diary for five weeks. As an Early Phase 1 trial, this research focuses on understanding how the treatment functions in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you have not used certain medications like antibiotics, systemic steroids, interleukins, systemic interferons, systemic chemotherapy, or probiotics in the past 30 days. If you are currently taking these, you may need to stop before joining the trial.

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

Research shows that using a live biotherapeutic product (LBP) with Lactobacillus crispatus is generally safe. In past studies, women who used similar LBPs, like LACTIN-V, experienced fewer recurrences of bacterial vaginosis (BV) compared to those who did not receive the treatment. Importantly, these studies found that the products were well-tolerated, with most participants not experiencing serious side effects.

For the specific multi-strain LBPs tested in this trial, previous research showed that these products are safe and easy to use. Additionally, they established lasting colonization, meaning the beneficial bacteria remained in the body for a while after the treatment ended.

Since this trial is in its early phase, the main focus is on carefully assessing safety. Researchers closely monitor any potential side effects or adverse reactions. However, based on earlier studies, the LBPs have shown a good safety profile so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these new treatments for bacterial vaginosis because they introduce a novel use of live biotherapeutic products featuring strains of Lactobacillus crispatus. Unlike the standard antibiotics like metronidazole, which eliminate bacteria indiscriminately, these treatments aim to restore and maintain a healthy vaginal microbiome by specifically boosting beneficial bacteria. The investigational treatments vary in their approach: some use six strains of L. crispatus and differ in duration, while another uses fifteen strains for a potentially more robust probiotic effect. This targeted method offers hope for reducing recurrence rates and improving long-term outcomes for patients.

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

Research has shown that Lactobacillus crispatus can effectively treat bacterial vaginosis (BV). One study reported that a vaginal product with L. crispatus achieved an 80% success rate in treating BV, compared to 59% with a placebo. Another study found that L. crispatus grew well in the vagina, suggesting it can help maintain a healthy balance and prevent BV from recurring. In this trial, participants may receive the LC106 product, containing 6 strains of L. crispatus, or the LC115 product, containing 15 strains. Specifically, women using the LC115 product experienced a significant increase in L. crispatus, which supports vaginal health. These findings suggest that both LC106 and LC115 could be promising options for reducing BV recurrence and improving vaginal health. ^{1 6 7 8 9}

Who Is on the Research Team?

Caroline Mitchell, MD, MPH

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for premenopausal individuals aged 18-40 with bacterial vaginosis, as confirmed by specific criteria. They must be willing to follow the study procedures, not pregnant or breastfeeding, HIV negative, and on certain contraceptives. Exclusions include significant reproductive tract diseases, recent antibiotic use or infections other than BV, certain medication use within the last month, and any condition that may affect participation.

Inclusion Criteria

You are able to and agree to sign a paper saying you understand and agree to be in the study.

You are not pregnant and are not likely to become pregnant based on your last period and recent sexual activity, as determined by a doctor.

You have at least 3 of 4 specific symptoms that indicate a certain condition (BV).

Exclusion Criteria

Syphilis (positive screen at enrollment)

History of coronary artery disease, myocardial infarction, chronic obstructive pulmonary disease, chronic renal failure, decompensated cirrhosis, or any other condition that in the opinion of the investigator will compromise ability to participate in the study

Use of an IUD (intrauterine device)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Antibiotic Treatment

Participants receive 7 days of oral metronidazole (500mg twice daily) for bacterial vaginosis

1 week

1 visit (in-person) for prescription and instructions

Vaginal Biotherapeutic Treatment

Participants receive either placebo or L. crispatus live biotherapeutic product for 7 days, with different dosing strategies

1 week

Daily home swabs and diary entries

Follow-up

Participants are monitored for safety and effectiveness, including adverse events and colonization kinetics

12 weeks

Regular follow-up visits and assessments

What Are the Treatments Tested in This Trial?

Interventions

• LC106
• LC115
• Metronidazole Oral
• Placebo

Trial Overview The trial tests two vaginal live biotherapeutic products (LBPs) containing different strains of L. crispatus (LC106 & LC115) against a placebo in people treated with antibiotics for BV. It aims to see if these LBPs are safe and can colonize the vagina post-treatment.

How Is the Trial Designed?

Group I: LC115 Experimental Treatment 2 Interventions

Vaginal live biotherapeutic product with 15 strains of L. crispatus, administered daily for 7 days after antibiotic treatment

Group II: LC106 7 days, early start Experimental Treatment 2 Interventions

Vaginal live biotherapeutic product with 6 strains of L. crispatus, administered daily for 7 days starting on the 3rd day of antibiotic treatment

Group III: LC106 7 days Experimental Treatment 2 Interventions

Vaginal live biotherapeutic product with 6 strains of L. crispatus, administered daily for 7 days after antibiotic treatment

Group IV: LC106 3 days Experimental Treatment 2 Interventions

Vaginal live biotherapeutic product with 6 strains of L. crispatus, administered daily for 3 days after antibiotic treatment and packaged with 4 tablets of placebo to maintain masking (so a total of 7 tablets)

Group V: Placebo Placebo Group 2 Interventions

Vaginal placebo tablet administered daily for 7 days starting after antibiotic treatment

Metronidazole Oral is already approved in United States, European Union, India, Canada for the following indications:

Approved in United States as Flagyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Approved in European Union as Flagyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Approved in India as Metrogyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Approved in Canada as Flagyl for:

• Pelvic inflammatory disease
• Endocarditis
• Bacterial vaginosis
• Dracunculiasis
• Giardiasis
• Trichomoniasis
• Amebiasis
• Clostridioides difficile colitis

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Ragon Institute of MGH, MIT and Harvard

Collaborator

Trials

9

Recruited

1,600+

Bill and Melinda Gates Foundation

Collaborator

Trials

428

Recruited

23,060,000+

Centre for the AIDS Programme of Research in South Africa

Collaborator

Trials

23

Recruited

20,800+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12495413/

Randomized trial of multi-strain Lactobacillus crispatus ... These results suggest that 1) vaginal inoculation with L. crispatus can decrease recurrent clinical BV, and 2) inoculating a single strain of L. crispatus might ...

2. nature.com nature.com/articles/s41522-025-00788-6

Vaginal Synbiotic Impact on Microbiome: RCT Results indicate that L. crispatus successfully colonized individuals who received the multi-strain synbiotic vaginal tablet, and that ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06135974

Study Details | NCT06135974 | Vaginal lIve Biotherapeutic ... The study will evaluate one LBP with 6 strains of L. crispatus (LC106) and one LBP with 15 strains (LC115) vs. placebo. Participants will: be treated with oral ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9061781/

opportunities for bacterial vaginosis treatment One L. crispatus clinical trial showed promising results for BV, with an 80% remission rate compared with a 59% remission rate in the placebo ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589004225017341

Lactobacillus-rich cervicovaginal microbiome associated ... The cervicovaginal microbiome modulates susceptibility to bacterial vaginosis (BV), high-risk human papillomavirus (hrHPV) infection, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2451865425001280

Randomized trial of multi-strain Lactobacillus crispatus ... Clinically, women treated with LACTIN-V had a significantly lower risk for recurrent BV at both 12 and 24 weeks. These results suggest that 1) ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41050878/

Randomized trial of multi-strain Lactobacillus crispatus ... Methods: This is a Phase 1, randomized, placebo-controlled trial of vaginal live biotherapeutic products (LBP) after antibiotic treatment for BV to establish ...

8. thelancet.com thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00305-7/fulltext

Effect of the vaginal live biotherapeutic LACTIN-V ... This randomised, placebo-controlled, phase 2 trial evaluated LACTIN-V (L crispatus CTV-05), a vaginal live biotherapeutic, compared with placebo ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1915254

Randomized Trial of Lactin-V to Prevent Recurrence ... The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at ...