Vaginosis, Bacterial, Bacterial Vaginosis, Bacterial Vaginosis (BV)
Conditions
Keywords
Recurrence, Microbiome, Metronidazole, Bacterial Vaginosis
Brief summary
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_SUPPLEMENTLactobacillus 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_SUPPLEMENTPlacebo (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.
Sponsors
Kaneka Americas Holding Inc.
Vedic Lifesciences Pvt. Ltd.
AB-Biotics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Masking description
Both treatments look, taste and feel the same and are packed in exact same envelope.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Day 6 to Day 180 | Amsel criteria (≥3 out of 4 positive) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of BV recurrences diagnosed using Nugent score (≥ 7) (main secondary endpoint) | Day 6 to Day 180 | Compared to Placebo |
| Analysis of BV recurrences diagnosed using both Amsel criteria (≥ 3 of 4 positive) and Nugent score (≥7) | Day 6 to Day 180 | Compared to placebo |
| Time to first BV recurrence as per Amsel's criteria (≥3 of 4 positive) and/or Nugent Score (≥7) | Day 6 to Day 180 | Compared to Placebo |
| Proportion of participants experiencing 2 or more, and 3 or more BV infections during the study period. | Day 6 to Day 180 | Compared to Placebo |
| Percentage of patients receiving first-line or second-line SOC and duration (days). | Day 6 to Day 180 | Compared to Placebo |
| Absolute difference in the duration of the SOC consumption (days). | Day 6 to Day 180 | Compared to Placebo |
| Reducing the duration and severity of symptoms (itching, vaginal discharge, and odor) assessed by Visual Analogue Scale (VAS). | 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). | Compared to Placebo |
| Percentage of patients with recovery of normal Nugent score (0-3). | Day 6 to Day 22 | Compared to Placebo |
| Vaginal health by International Consultation on Incontinence Questionnaire - Vaginal symptoms (ICIQ-VS). | Day 0, Day 6, Day 22, Day 90 and Day 180 | Compared to Placebo |
| Change in vaginal pH assessed by vaginal pH strip method. | 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). | Compared to Placebo |
| Concentration of proinflammatory cytokines. | Day 0, Day 22 | Compared to Placebo |
| Relative abundances of lactobacilli and common pathogens associated to BV assessed by using Next-Generation Sequencing (NGS). | Day 0, Day 6, Day 22, Day 90, Day 180 | Compared to Placebo |
| Percentage of women with vaginal Community State Types (CSTs) associated to healthy vaginal microbiota. | Day 0, Day 6, Day 22, Day 90, Day 180 | Compared to Placebo |
| Analysis of BV recurrences (including intermediate BV) as confirmed per Amsel criteria (≥ 3 of 4 positive) and Nugent score (score≥4) throughout the 6-month period. | Day 6 to Day 180 | Compared to Placebo |
| Analysis of BV recurrences (including intermediate BV) as confirmed per Nugent score (score ≥4) throughout the 6-month period. | Day 6 to Day 180 | Compared to Placebo |
Contacts
CONTACTMaria Rodriguez-Palmero, PhD
CONTACTNúria Gispets Parés
Outcome results
None listed