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

August 15, 2026 updated by: Dr. Amjad Khan, Liaquat University of Medical & Health Sciences

Oral Lactobacillus Crispatus M247 as an Add-on to Enterococcus Faecium L3 and Bifidobacterium Animalis Subsp. Lactis BB-12 for the Prevention of Recurrent Urinary Tract Infections in Women: A Prospective Randomized Controlled 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
84

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Rome (RM)
      • Rome, Rome (RM), Italy, 00168
        • Complex Operating Unit of Surgical Gynecology and Pelvic Floor Reconstructive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cumulative number of symptomatic UTI recurrences per participant
Time Frame: 12 months
Cumulative number of investigator-confirmed, urine-culture-supported symptomatic UTI recurrences experienced by each participant from randomization through the 12-month follow-up
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in urinary symptoms (King's Health Questionnaire)
Time Frame: Baseline, 3 months
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 health-related quality of life (EQ-5D)
Time Frame: Baseline, 3 months
Assessment using the EuroQol 5-Dimension questionnaire (EQ-5D). The individual health dimensions and perceived health status were assessed separately.
Baseline, 3 months
Change in sexual function
Time Frame: Baseline, 3 months
Assessment using the Female Sexual Function Index-6 (FSFI-6). The available sexual-health measures were assessed separately.
Baseline, 3 months
Treatment adherence
Time Frame: 3 months
Proportion of participants taking at least 90% of the scheduled doses of the assigned probiotic supplementation, assessed using participants' treatment diaries and counts of returned unused sachets.
3 months
Treatment tolerability
Time Frame: 3 months
Participants' overall assessment of treatment tolerability, categorized as excellent, good, fair, or poor, together with the number of treatment discontinuations.
3 months
Safety and adverse events
Time Frame: 12 months
Number and proportion of participants experiencing adverse events, serious adverse events, vaginitis, bacterial vaginosis, or other genital infections during the study.
12 months
Participants experiencing at least one symptomatic UTI recurrence through month 3
Time Frame: 3 months
Number and proportion of participants experiencing at least one investigator-confirmed, urine-culture-supported symptomatic UTI recurrence from randomization through the 3-month assessment.
3 months
Participants experiencing at least one symptomatic UTI recurrence through month 12
Time Frame: 12 months
Number and proportion of participants experiencing at least one investigator-confirmed, urine-culture-supported symptomatic UTI recurrence from randomization through the 12-month assessment.
12 months
Pelvic pain and urgency/frequency symptom burden at month 3
Time Frame: 3 months
Assessment using the Pelvic Pain and Urgency/Frequency (PUF) questionnaire. Total scores range from 0 to 35, with higher scores indicating greater symptom severity.
3 months
Cumulative number of symptomatic UTI recurrences per participant through month 3
Time Frame: 3 months
Cumulative number of investigator-confirmed, urine-culture-supported symptomatic UTI recurrences experienced by each participant from randomization through the 3-month assessment.
3 months
Participants requiring culture-guided antibiotic therapy for a symptomatic UTI recurrence
Time Frame: 12 months
Number and proportion of participants experiencing at least one investigator-confirmed, urine-culture-supported symptomatic UTI recurrence whose symptoms did not improve to a clinically meaningful extent within 3 days of an initial non-antibiotic regimen. This regimen comprised oral D-mannose 500 mg three times daily, taken after voiding and away from meals, together with ibuprofen 400 mg once daily in the morning after breakfast, with a second 400-mg dose 12 hours later when required. Participants reporting an allergy to ibuprofen received paracetamol 1,000 mg once daily, with a second 1,000-mg dose 12 hours later when required. Participants without clinically meaningful improvement by day 3 received antibiotic therapy selected according to urine-culture and antimicrobial-susceptibility results. The denominator was the number of participants experiencing at least one confirmed recurrence; each participant was counted only once if antibiotic therapy was required for any recurrence.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Liaquat University of Medical & Health Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 5, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 11, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 11, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 22, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 4, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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