Study to Evaluate Efficacy and Safety of Gyntima® Balance in Preventing Recurrences of Bacterial Vaginosis

Official title

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Gyntima® Balance in Preventing Recurrences of Bacterial Vaginosis.

Overview

The vagina is a dynamic muscular organ whose health relies on a Lactobacillus-dominant microbiota that maintains low pH and protects against infections. Bacterial vaginosis (BV) is the most common vaginal imbalance in women of reproductive age, caused by depletion of protective Lactobacillus species and overgrowth of anaerobic bacteria such as Gardnerella vaginalis. BV affects an estimated 23-29 percentage of women globally (10-30 percentage in India) and is associated with discharge, odor, discomfort, and significant risks including recurrent disease, adverse reproductive outcomes, and increased susceptibility to STIs. Although antibiotics are effective for acute treatment, recurrence rates are high (50-60 percentage within 12 months), highlighting an unmet need for preventive strategies. Probiotics, particularly Lactobacillus species, have emerged as promising options to restore vaginal microbiota balance and reduce BV recurrence. Lactobacillus gasseri is a natural vaginal commensal with antimicrobial activity against BV pathogens and the ability to lower vaginal pH. L. gasseri KABP®064 has demonstrated vaginal colonization after oral administration, good tolerability, and potential to promote vaginal health. The present randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of oral L. gasseri KABP®064 in preventing BV recurrence over six months following standard antibiotic therapy. Outcomes include recurrence rates and timing, symptom severity, microbiological balance, inflammation markers, and patient-reported vaginal health, supporting a microbiome-focused, non-antibiotic approach to BV recurrence prevention.

Interventions

• Dietary supplement Lactobacillus gasseri KABP®064 10e9 CFU/capsule
  Phase 1: 15 days, 1 capsule/day post-randomization. Phase 2: 10 days per month for \~6 months, starting 6th day of menstruation, 1 capsule/day.
• Dietary supplement Placebo (maltodextrin)
  Phase 1: 15 days, 1 capsule/day post-randomization. Phase 2: 10 days per month for \~6 months, starting 6th day of menstruation, 1 capsule/day.

Primary outcome measures

• To evaluate the efficacy of Lactobacillus gasseri KABP®064 in preventing recurrence of BV infections, diagnosed using Amsel criteria, over a period of 6 months as compared to placebo. [Time frame: Day 6 to Day 180]

Secondary outcome measures (12)

• Analysis of BV recurrences diagnosed using Nugent score (≥ 7) (main secondary endpoint) [Time frame: Day 6 to Day 180]
• Analysis of BV recurrences diagnosed using both Amsel criteria (≥ 3 of 4 positive) and Nugent score (≥7) [Time frame: Day 6 to Day 180]
• Time to first BV recurrence as per Amsel's criteria (≥3 of 4 positive) and/or Nugent Score (≥7) [Time frame: Day 6 to Day 180]
• Proportion of participants experiencing 2 or more, and 3 or more BV infections during the study period. [Time frame: Day 6 to Day 180]
• Percentage of patients receiving first-line or second-line SOC and duration (days). [Time frame: Day 6 to Day 180]
• Absolute difference in the duration of the SOC consumption (days). [Time frame: Day 6 to Day 180]
• Reducing the duration and severity of symptoms (itching, vaginal discharge, and odor) assessed by Visual Analogue Scale (VAS). [Time frame: Day 0, Day 6, Day 22, Day 90, Day 180, and at recurrence visits (if patients have a BV recurrence during the study time frame, they will ask for a "recurrence visit" to assess medication and some study parameters).]
• Percentage of patients with recovery of normal Nugent score (0-3). [Time frame: Day 6 to Day 22]
• Vaginal health by International Consultation on Incontinence Questionnaire - Vaginal symptoms (ICIQ-VS). [Time frame: Day 0, Day 6, Day 22, Day 90 and Day 180]
• Change in vaginal pH assessed by vaginal pH strip method. [Time frame: Day 0, Day 6, Day 22, Day 90, Day 180, and at recurrence visits (if patients have a BV recurrence during the study time frame, they will ask for a "recurrence visit" to assess medication and some study parameters).]
• Concentration of proinflammatory cytokines. [Time frame: Day 0, Day 22]
• Relative abundances of lactobacilli and common pathogens associated to BV assessed by using Next-Generation Sequencing (NGS). [Time frame: Day 0, Day 6, Day 22, Day 90, Day 180]

Eligibility criteria

Inclusion criteria

• Females of ages 18-45 years (both values included) who are premenopausal.
• History of recurrent BV (at least 3 episodes in the last 12 months with at least one of them documented in the last 6 months).
• Positive Amsel's criteria (confirming active BV) determined by at least 3 out of the following 4 symptoms or signs:

• Homogeneous, thin, yellowish-white/greyish white discharge that smoothly coats the vaginal walls.
• Presence of the clue cells on microscopic examination (as assessed by wet mount test).
• A fishy odor of vaginal discharge after adding 10% potassium hydroxide (KOH) solution to wet mount - also known as "whiff test".
• Vaginal pH > 4.5
• Imbalance in vaginal pH (pH > 4.5).
• Participants with Body Mass Index (BMI) 18.5-32.0 kg/m2.
• Non-smokers.
• Participants able to comply with and perform the procedures requested by the protocol (including dietary restrictions, consumption of study treatments, blood and urine sample collection procedures and study visit schedule).
• Participants who are literate enough to understand the essence of study, are informed about the purpose of the study, and understand their rights.
• Participants able to give written informed consent and willingness to participate in the study and comply with its procedures.

Exclusion criteria

• Participants currently taking contraceptives and/or sexual hormones.
• Pregnant or breastfeeding.
• Menstrual period expected within the next 6 days of screening.
• Irregular cycle ("irregular" (e.g., less than 21 or more than 35 days consistently, or cycle variability more than 4 days month-to-month).
• Participants who have documented resistance to metronidazole.
• Participants diagnosed with any vaginal or urinary tract infection other than BV.
• Participants who have used other probiotics or antibiotics (vaginal, oral, parenteral) in the last 15 days.
• Participants using other vaginal products with bacteriostatic or bactericide activity (such as lactic acid gels, herbal extracts, dequalinum chloride, etc.).
• Participants with an intrauterine contraceptive device (IUCD/IUD) in situ at screening.
• Participants who have undergone total hysterectomy or any other surgery involving the female reproductive system.
• Women diagnosed with Sexually transmitted infections (STIs) or Human immunodeficiency virus (HIV) infection.
• Participants diagnosed with Polycystic ovary syndrome (PCOS) or other such diseases that further affect the hormonal homeostasis in women.
• Presence of uncontrolled diabetes mellitus (Indicated by Fasting Blood Glucose (FBG) more than or equal to 126 mg/dL. Fasting is defined as no caloric intake for at least 8 hours).
• Presence of uncontrolled hypertension (Defined as Systolic Blood Pressure (SBP) more than or equal to 140 mm Hg and/or Diastolic Blood Pressure (DBP) more than or equal to 90 mm Hg).
• Untreated previously diagnosed thyroid disorders.
• Participants who have a history of any significant neurological and psychiatric condition which may affect the participation and inference of the study's end points.
• Participation in other clinical trials in last 3 months prior to screening.
• Participants with substance abuse problems defined as:

• High-risk drinking as defined by consumption of 4 or more alcohol containing beverages on any Day or 8 or more alcohol containing beverages per week for women.
• Participants who have any of the following clinically significant illness, i.e., Cardiovascular, endocrine system, immune system, respiratory system, hepatobiliary system, kidney and urinary system, neuropsychiatric, musculoskeletal, inflammatory, blood and tumors, chronic gastrointestinal diseases, etc.
• Any condition that could, in the opinion of the Investigator, preclude the participant's ability to successfully and safely complete the study or that may confound study outcomes.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07527572 · 241002/IP/BV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗