Genitourinary Study of Fostering Lactobacillus to Optimize the Microbiome in Women's Health (GUD-FLORA) (GUD-FLORA)

The objective of this study is to evaluate the use of a vaginal probiotic in patients with recurrent urinary tract infections (UTIs). Specifically, this study aims to evaluate factors associated with successful colonization with Lactobacillus crispatus - a known "healthy" and protective bacteria in both the vaginal and urinary microenvironments. The study will recruit patients over age 18 with a clinical diagnosis of recurrent UTIs, and will utilize a commercially available Lactobacillus vaginal probiotic. Participants will use the probiotic product with the commercially approved packaging and regimen for a total of 3 months. Vaginal and urinary samples will be obtained at four different timepoints. Participants will also be asked to complete surveys regarding tolerability and acceptability of the probiotic product. Patient samples will be analyzed in the laboratory to understand the effects of the probiotic on the local microbiome. Survey data and demographic information will be housed within the Research Electronic Data Capture (RedCap) secure server. For our primary analysis, Lactobacillus crispatus (L. crispatus) abundance will be measured and used as the outcome variable in a linear regression model evaluating the impact of baseline patient and microbiome characteristics on L. crispatus colonization.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent UTIs
• Intervention / Treatment: Drug: Lactobacillus crispatus probiotic

Detailed Description

This is a prospective, observational study in patients with recurrent UTIs seeking care in the Duke Division of Urogynecology.

After obtaining informed consent, baseline samples and questionnaires will be completed during an in person visit. Clinical data will be abstracted from the medical record. At the baseline visit, participants will be supplied a 3-month course of the VS-01TM vaginal probiotic, manufactured by Seed Health, Inc. VS-01TM is a commercially available dissolving tablet containing three strains of L. crispatus. The tablet is self-administered vaginally via a supplied applicator.

Participants will follow the recommended dosing regimen (e.g., Days 1, 4, 7, 14, 21, 28, then every other week) to total 3 months.

No existing patient therapies for recurrent UTIs will be discontinued or prohibited during the study period. Patients will be encouraged to continue any stable/existing medications for UTI prevention such as vaginal estrogen. No placebo control will be utilized.

Participants will be supplied with at-home sampling kits for sample collection. Final sampling occurs once month after completion of the probiotic regimen, with samples banked for future analyses to determine whether colonization persists after cessation of the probiotic. Sampling will occur at baseline and at weeks 4, 10, and 16. Each sampling time point will include a urine sample and a vaginal swab. The baseline sample will also include a pH test via pH paper strip.

Home sampling procedures will be similar to those recently published by a large consortium. Participants will return sampling kits via pre-paid, pre-addressed shippers through our laboratory account. Due to the at-home nature of patient sample collection, no additional visits to clinic will be required. Patients will have access to routine clinic visits per standard of care.

Upon receipt in the lab, samples will be processed, and DNA will be extracted. Prepared samples with positive and negative controls will be evaluated for microbial abundance. For our primary analysis, absolute abundance of L. crispatus at baseline and subsequent timepoints will be evaluated using digital droplet PCR. In addition, the investigators will plan to pursue additional funding for sequence-based analyses of L. crispatus and other species. For these additional analyses, samples would be submitted to the Duke Microbiome Core for library preparation, amplification, and sequencing of the full-length 16S rRNA gene. Taxonomic identification will be performed with standard pipelines and relative abundance of L. crispatus and other species will be quantified.

With respect to survey data, all will be completed electronically either in clinic (baseline via iPads), or at home (link sent to designated email), and stored through Research Electronic Data Capture (REDCap). The questionnaires utilized are the Vulvovaginal Symptoms Questionnaire (VSQ) and an acceptability questionnaire. These are validated questionnaires to assess patient tolerability and acceptability, respectively, of the vaginal probiotic regimen.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Elizabeth Howell; Phone Number: 919-684-8111; Email: elizabeth.howell@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• English-speaking
• ≥ 18 years of age
• Diagnosed with recurrent urinary tract infections (UTIs). Specifically, participants will have had 3 UTIs over the past 12 months or 2 UTIs over the past 6 months. At least one of these UTIs must be culture-proven. For UTIs to count for this study, if not culture-proven they must involve the onset of UTI-related symptoms (dysuria, urgency, frequency, suprapubic pain, or urinary changes, etc) with prescription of antibiotics directed at UTI treatment.

Exclusion Criteria

• Chronically self-catheterize.
• Currently use of a vaginal pessary.
• Have used a vaginal probiotic in the prior 3 months.
• Are pregnant or within 1 year postpartum.
• Have poorly controlled diabetes with an A1c of 9 or greater.
• Are considered immunocompromised
• Are unable to personally provide legal consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic Group; All patients will receive vaginal probiotic product	Drug: Lactobacillus crispatus probiotic; Probiotic arm (all patients); Other Names: Probiotic; VS-01(TM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative abundance	The primary endpoint is relative abundance of vaginal L. crispatus after several months of vaginally inserted L. crispatus probiotics.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Vaginal - Urinary Correlation	Correlations in vaginal and urinary L. crispatus, at baseline and several timepoints after initiation and cessation of probiotic.	Baseline, 4, 10, and 16 weeks
Tolerability of a vaginal probiotic regimen as measured by the Vulvovaginal Symptoms Questionnaire (VSQ)	A higher score on the VSQ (range of 0 to 21) indicates lower tolerability.	Baseline, 4, 10, and 16 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Nazema Siddiqui, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Microbiome; Probiotic; Lactobacillus; Urinary tract infection; Recurrent UTI; Vaginal probiotic
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Urinary Tract Infections; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Probiotics
• Other Study ID Numbers: Pro00118524

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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