Effect of a Multi-strain Probiotic on Recurrent Vulvovaginal Candidiasis (PROVELIA)

A Pilot Clinical Trial Assessing the Effect of a Multi-strain Probiotic on the Risk of Recurrence and Severity of Symptoms in Females With Recurrent Vulvovaginal Candidiasis

This study evaluates the effect of a multi-strain probiotic on the risk of recurrence and severity of symptoms in females with recurrent vulvovaginal candidiasis (R-VVC).

Study Overview

• Status: Recruiting
• Conditions: Vulvovaginal Candidiasis
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

Detailed Description

This study aims to investigate the efficacy of live bacteria on the incidence and severity of symptoms of vulvovaginal candidiasis (VVC) recurrence. The trial will be run in India and recruit women with recurrent vulvovaginal candidiasis (R-VVC).

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: ADM Medical Team; Phone Number: +441460243230; Email: medical@protexin.com
• Study Contact Backup: Name: Sanjay Dr Vaze, MBBS, MD; Phone Number: +9102242172325; Email: sanjay.v@vediclifesciences.com

Study Locations

• India
  • Gujarat
    • Vadodara, Gujarat, India
      • Recruiting
      • Anand Multispeciality Hospital
  • Maharashtra
    • Nashik, Maharashtra, India
      • Recruiting
      • Life care Hospital
    • Pune, Maharashtra, India
      • Recruiting
      • AMF's Moraya Multispeciality Hospital
    • Pune, Maharashtra, India
      • Recruiting
      • ENT & Vertigo Clinic
    • Sopara, Maharashtra, India
      • Recruiting
      • Vivaan Hospital
    • Vasai, Maharashtra, India
      • Recruiting
      • Matritva Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Individuals meeting ALL of the following criteria will be enrolled for the study:

1. Premenopausal women aged 18-50 years.
2. Women with a culture-confirmed active episode caused by Candida spp. (albicans or non-albicans) reported within 24-48 hours of evidence of clinical symptoms. (No medications should have been initiated before the sample for culture is collected).
3. Documented history of recurrence of at least 3 VVC episodes in the last 12 months confirmed by vaginal culture /clinical diagnosis.
4. Culture growth of Candida spp. causing VVC.
5. Random Capillary Blood Glucose of < 110mg/dl.
6. Willingness to consume the study products for the entire study duration.
7. Willing to complete all study procedures and comply with study requirements.
8. Willing to abstain from other supplements or medication.
9. Ready to give voluntary, written, informed consent to participate in the study.

Exclusion Criteria:

Individuals meeting ANY of the following criteria will be excluded from the study:

1. Post-menopausal and peri-menopausal women.
2. Pregnant/breast-feeding women.
3. Use of oral or vaginal anti-fungal medication in the last 14 days.
4. Vaginal culture suggestive of bacterial vaginosis (Nugent's score of 7-10), trichomonas vaginalis or Gardnerella vaginalis.
5. Participants found positive for Clotrimazole resistance, by vaginal culture & sensitivity at screening.
6. Known allergy to Clotrimazole.
7. Women not willing to use any form of vaginal medication during the study.
8. Use of vaginal douching.
9. Unwillingness to use an appropriate method of contraception.
10. Diagnosed with compromised immune system, type I and/or type II diabetes mellitus, or malignancies.
11. Use of corticosteroids therapy in the last 30 days.
12. Use of oral/systemic antimicrobial therapy in the last 30 days.
13. Known allergy to the study products or azoles.
14. Individuals with a history of frequent infections requiring antibiotic treatments.
15. Participation in another clinical study(ies) in the last 3 months.
16. Women who, in the opinion of the Investigator, are considered to be poor clinical attendees or unlikely for any reason to be able to comply with the study.
17. Women with uncontrolled hypertension with systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg.
18. Heavy alcohol drinkers defined as follows: For men, consuming more than 4 drinks on any day or more than 14 drinks/week. For women, consuming more than 3 drinks on any day or more than 7 drinks/week.
19. Smokers.
20. History or presence of clinically significant renal, hepatic, endocrine, biliary, gastrointestinal, pancreatic or neurologic disorders that, in the judgment of the Investigator, would interfere with the participant's ability to provide informed consent, comply with the study protocol (which might confound the interpretation of the study results), or put the individual at undue risk.
21. Presence of unstable, acutely symptomatic, or life-limiting illness.
22. Use of any supplements (includes probiotics, post-biotics, herbal supplements, synbiotics, enzyme supplements, vitamins with probiotics) in the last 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; Participants in this arm will receive a daily dose of 2x10^9 Colony Forming Units (CFU) of a multi strain probiotic (live bacterium), corresponding to 2 capsules once daily, for 6 months.	Dietary supplement: Probiotic; Participants in this arm will receive a daily dose of 2x10^9 Colony Forming Units (CFU) of a multi strain probiotic (live bacterium), corresponding to 2 capsules once daily, for 6 months.
Placebo Comparator: Placebo; Participants in this arm will receive an equivalent placebo for the duration of the study (6 months).	Dietary supplement: Placebo; Participants in this arm will receive an equivalent placebo for the duration of the study (6 months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of culture-confirmed VVC recurrence between baseline and day 180 as compared to placebo.	Efficacy of a multi-strain probiotic on incidence of culture-confirmed VVC recurrence as compared to placebo, where VVC recurrence is defined as a fungal culture positive vaginal swab with at least 2 moderate VVC related symptoms or at least 1 severe VVC related symptom and with VVC free period prior to this incident of at least 7 days.	Day 0, Day 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of culture-confirmed VVC recurrence between baseline and day 90 as compared to placebo.	Efficacy of a multi-strain probiotic on incidence of culture-confirmed VVC recurrence as compared to placebo, where VVC recurrence is defined as a fungal culture positive vaginal swab with at least 2 moderate VVC related symptoms or at least 1 severe VVC related symptom and with VVC free period prior to this incident of at least 7 days.	Day 0, Day 90
Time to first recurrence of VVC episode from baseline between probiotic and placebo groups.	Time to first recurrence of VVC episode from baseline between probiotic and placebo groups, where VVC recurrence is defined as a fungal culture positive vaginal swab with at least 2 moderate VVC related symptoms or at least 1 severe VVC related symptom and with VVC free period prior to this incident of at least 7 days.	Day 0 to first VVC recurrence
Change in the number of days with VVC episode between probiotic and placebo groups.	Efficacy of a multi-strain probiotic on the number of days with VVC episode as compared to placebo group, where VVC episode is defined as a fungal culture positive vaginal swab with at least 2 moderate VVC related symptoms or at least 1 severe VVC related symptom and with VVC free period prior to this incident of at least 7 days.	Duration (days) of VVC episodes, Day 0-180.
Change in severity of VVC episodes between probiotic and placebo groups.	Efficacy of a multi-strain probiotic on the severity of VVC episodes as assessed by symptoms (itching/soreness, edema, dysuria, vaginal discharge, dyspareunia, erythema, fissures/excoriations) severity on a 4-point Likert Scale as compared to baseline and placebo. The number of days of an episode will be captured using the e-dairy. First day of the episode will be considered as the day when the participant experiences onset of at least 2 moderate symptoms or at least one severe symptom on the 4-point Likert scale. The last day of the episode will be considered when there is no presence of VVC related clinical signs and symptoms and thus the composite score on the Likert scale is 0.	During VVC episodes
Proportion of Candida albicans positive VVC episodes vs other pathogens between probiotic and placebo groups.	Efficacy of a multi-strain probiotic on proportion of Candida albicans positive VVC episodes vs other pathogens.	During VVC episodes
Number of administrations of vaginal pessaries during acute VVC episodes as compared to baseline and placebo.	Number of vaginal pessaries applied during acute VVC episodes as compared to baseline and placebo. A Clotrimazole 100 mg pessary to be applied once daily at bedtime till no symptoms persist.	During VVC episodes
Changes in vaginal health as assessed by vaginal pH and compared to baseline and placebo.	Changes in vaginal health as assessed by vaginal pH, compared to baseline and placebo, using pH strips.	Day 0, Day 90, Day 180
Changes in vaginal microbiology as assessed by vaginal Candida albicans culture and compared to baseline and placebo.	Changes in vaginal microbiology as assessed by vaginal Candida albicans culture and compared to baseline and placebo.	During episodes
Quality of life as assessed using SF-36 and compared to baseline and placebo.	Changes in quality of life as assessed using SF-36 and compared to baseline and placebo. Total and individual scoring of the 8 sections of the SF-36 questionnaire will be used to infer the improvement in quality of life improve. A high score defines a more favorable health state (maximum score 100).	Day 0, Day 90, Day 180

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Influence of multi-strain probiotic on vaginal microbiome as compared to baseline and placebo.	Effects of a multi-strain probiotic in vaginal microbiome as assessed by shotgun analysis and compared to baseline and placebo.	Day 0, Day 90, Day 180

Collaborators and Investigators

• Sponsor: The Archer-Daniels-Midland Company
• Collaborators: Vedic Lifesciences Pvt. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): June 28, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Infection; Microbiome; Candidiasis; Probiotic; Chronic; Recurrent; Vaginal; Vulvovaginal; RVVC
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Genital Diseases, Female; Bacterial Infections and Mycoses; Vulvar Diseases; Vulvitis; Vaginitis; Mycoses; Vaginal Diseases; Vulvovaginitis; Candidiasis; Candidiasis, Vulvovaginal
• Other Study ID Numbers: CTB2022TN202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No