Study to Evaluate the Efficacy of Lactobacillus Crispatus M247 in the Prevention and Treatment of Recurrent Urinary Tract Infections

Interventional Study on the Efficacy of Lactobacillus Crispatus M247 for Prevention and Treatment of Recurrent Urinary Tract Infections in Combination With Enterococcus Faecium L3 and Bifidobacterium Animalis Subsp. Lactis BB-12 (URTI): A Randomized Controlled Pilot Trial

This randomized, open-label, controlled clinical trial evaluates the efficacy and safety of Lactobacillus crispatus M247 (CRISPACT®) in preventing recurrent urinary tract infections (rUTIs) in women. The study enrolls 84 adult female participants with a history of recurrent UTIs, defined as ≥3 episodes in the past year or ≥2 episodes in the past six months. Participants are randomized into two groups: the Probiotic Group, receiving iNatal Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3) for 30 days plus CRISPACT® (Lactobacillus crispatus M247) administered orally for 90 days; and the Control Group, receiving iNatal Duo® alone for 30 days without additional probiotic supplementation. The primary outcome is the reduction in the frequency of rUTIs over 12 months, while secondary outcomes include symptom improvement, quality of life, and safety assessments.

Study Overview

• Status: Completed
• Conditions: Recurrent Urinary Tract Infection
• Intervention / Treatment: Dietary supplement: Lactobacillus crispatus M247; Dietary supplement: iNatal-Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3)

Detailed Description

Recurrent urinary tract infections (rUTIs) represent a significant public health issue, disproportionately affecting women with hormonal fluctuations, sexual activity-related risks, or prior antibiotic exposure. Standard treatment relies on antibiotic therapy, which, while effective, contributes to antimicrobial resistance, microbiota imbalance, and increased recurrence risk. Probiotics, particularly Lactobacillus crispatus, have demonstrated potential in restoring urogenital microbiota balance and reducing uropathogen overgrowth.

This study aims to assess whether CRISPACT® (Lactobacillus crispatus M247), administered orally, provides superior protection against rUTIs compared with standard care using iNatal Duo® alone. The study follows a randomized, controlled design with 84 participants allocated to two parallel arms. The Probiotic Group receives iNatal Duo® for 30 days combined with CRISPACT® for 90 days, while the Control Group receives iNatal Duo® alone for 30 days without additional probiotic supplementation.

The primary objective is to evaluate the reduction in rUTI recurrence over a 12-month follow-up period, assessed through clinical diagnosis and patient-reported data. Secondary objectives include evaluation of symptom relief, patient-reported quality-of-life outcomes (EQ-5D, King's Health Questionnaire), and safety and tolerability of the probiotic intervention. The study seeks to provide clinical evidence supporting probiotic-based strategies for rUTI prevention and reduction of antibiotic dependence.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Varese, Italy
    • Medicine & Technological Innovation Dept. University of Insubria

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult women aged 18-65 years.
• History of recurrent urinary tract infections (rUTIs), defined as ≥3 episodes in the past year or ≥2 episodes in the past 6 months.
• Able to provide informed consent and comply with study procedures.

Exclusion Criteria:

• Age <18 years.
• Ongoing complicated cystitis or uncomplicated pyelonephritis.
• History of urological abnormalities or kidney stones.
• Recent sexually transmitted infection or bacterial vaginosis, or history of recurrent bacterial vaginosis.
• Risk factors for sexually transmitted diseases.
• Ongoing pregnancy, planning pregnancy, or breastfeeding.
• Diagnosis of diabetes mellitus.
• Diagnosis of HIV infection or other immunocompromised states.
• Recent history of drug or alcohol abuse.
• Persistent symptoms and/or pyuria after acute UTI treatment.
• Uterine, cervical, vaginal, or urethral cancer.
• Urethral diverticulum.
• Tuberculous, radiation-induced, cyclophosphamide-induced, or chemical cystitis.
• Benign or malignant bladder tumors.
• Recent diagnosis of vaginitis.
• Known hypersensitivity to study products.
• Failure to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRISPACT® Group; Participants in this group will receive iNatal Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3) 1 sachet per day orally for 30 days, along with CRISPACT® (Lactobacillus crispatus M247) administered orally for 90 days. The intervention aims to assess whether probiotic therapy reduces the frequency of recurrent urinary tract infections (rUTIs) over a 12-month follow-up period compared with control treatment.	Dietary supplement: Lactobacillus crispatus M247; CRISPACT® (Lactobacillus crispatus M247), PharmExtracta S.p.A; Dietary supplement: iNatal-Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3); iNatal-Duo®, PharmExtracta S.p.A
Active Comparator: Control Group; Participants in this group will receive iNatal-Duo® alone 1 sachet per day orally for 30 days without additional probiotic supplementation. This group will serve as a control to evaluate the comparative effectiveness of probiotic supplementation in preventing rUTI recurrence.	Dietary supplement: iNatal-Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3); iNatal-Duo®, PharmExtracta S.p.A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of recurrent urinary tract infection (rUTI) episodes	The primary outcome assesses the number of clinically diagnosed recurrent urinary tract infection episodes during the 12-month follow-up period in participants receiving CRISPACT® (Lactobacillus crispatus M247) plus iNatal Duo® compared with those receiving iNatal Duo® alone.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Role of anamnestic factors on development of rUTIs	Number of antibiotic courses prescribed for management of rUTIs during the 12-month Assessment tool: Case Report Form (CRF) with anamnestic data.	Baseline, 3 months, 12 months
Change in urinary symptoms (King's Health Questionnaire)	Assessment using the King's Health Questionnaire (KHQ), a validated condition-specific questionnaire for urinary symptoms. Scores range from 0 to 100, with higher scores indicating worse symptom severity and impact on quality of life.	Baseline, 3 months
Change in pelvic pain and urgency/frequency symptoms	Assessment using the Pelvic Pain and Urgency/Frequency (PUF) questionnaire. Total scores range from 0 to 35, with higher scores indicating greater symptom severity.	Baseline, 3 months
Change in health-related quality of life (EQ-5D)	Assessment using the EuroQol 5-Dimension questionnaire (EQ-5D). Index values range from less than 0 to 1, with higher values indicating better health-related quality of life.	Baseline, 3 months
Change in sexual function	Assessment using the Female Sexual Function Index-6 (FSFI-6). Total scores range from 2 to 30, with higher scores indicating better sexual function.	Baseline, 3 months

Collaborators and Investigators

• Sponsor: Liaquat University of Medical & Health Sciences
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2025
• Primary Completion (Actual): April 11, 2026
• Study Completion (Actual): April 11, 2026

Study Registration Dates

• First Submitted: February 22, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 4, 2025

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Urinary Tract Infections
• Other Study ID Numbers: 0038288/22/07.12.2022

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