Efficacy of Probiotic Lactobacillus Crispatus M247 in Promoting High-risk Human Papillomavirus (HR-HPV) Infection Clearance and Modifying Vaginal Microbiota

Evaluation of the Efficacy of Lactobacillus Crispatus M247 Administration in Promoting Clearance of Genital HR-HPV Infection and Modulating the Vaginal Microbiota: A Multicenter, Randomized, Placebo-Controlled, Single-Blind, Longitudinal, Prospective Clinical Trial

This clinical trial evaluates the efficacy of the probiotic strain Lactobacillus crispatus M247 in promoting the clearance of genital high-risk human papillomavirus (HR-HPV) infection and restoring the balance of the vaginal microbiota. The study adopts a multicenter, randomized, single-blind, longitudinal, prospective design involving HR-HPV-positive patients. Primary outcomes include HR-HPV clearance rates and microbiota composition changes.

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus Infection
• Intervention / Treatment: Dietary supplement: Lactobacillus crispatus M247 (Crispact®); Other: Placebo

Detailed Description

This study investigates the potential benefits of Lactobacillus crispatus M247, a probiotic strain with proven ability to promote vaginal health, in the management of HR-HPV infections. Lactobacillus crispatus M247 has demonstrated superior probiotic properties, including the ability to produce lactic acid and hydrogen peroxide, which contribute to maintaining a stable vaginal microbiota and potentially inhibiting HR-HPV persistence.

Participants will be randomized to receive either Lactobacillus crispatus M247 or a placebo over a specified study period. The primary aim is to evaluate the probiotic's efficacy in enhancing HR-HPV clearance rates and restoring a balanced vaginal microbiota. Secondary objectives include assessing changes in cervical cytology and participant-reported outcomes on vaginal health. By focusing exclusively on the role of Lactobacillus crispatus M247, the study seeks to establish its clinical relevance in HR-HPV management and its potential as a therapeutic intervention.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Catania, Italy, 95121
    • Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-San Marco"
  • Lentini, Italy, 96016
    • Nuovo Ospedale di Lentini
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women aged 18-69 years.
• First diagnosis of HR-HPV infection via DNA-HPV screening.
• Cytology results showing ASC-US or LSIL.
• Negative colposcopy or biopsy (absence of lesions).
• Ability to provide written informed consent.

Exclusion Criteria:

• Prior HPV vaccination.
• History of cervical treatments for pre-neoplastic pathology.
• Cytology showing HSIL (High-Grade Squamous Intraepithelial Lesion) requiring treatment.
• Current treatment with antibiotics, immunomodulatory, or immunosuppressive therapies.
• Diagnosed immune system or neoplastic diseases requiring chemotherapy.
• Pregnancy, lactation, or planning to become pregnant within 6 months.
• Known hypersensitivity to product components.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Participants in the control group will receive a placebo identical in appearance and packaging to the experimental product, administered orally at a dose of one stick per day for 4 months.	Other: Placebo; The placebo does not contain the active probiotic strain and consists of inactive excipients.
Experimental: Probiotic supplement Lactobacillus crispatus M247 group; Participants in this group will receive probiotic supplement Lactobacillus crispatus M247 (Crispact®) in stick form, administered orally at a dose of one stick per day for 4 months. Each stick contains 20 billion CFU of L. crispatus M247.	Dietary supplement: Lactobacillus crispatus M247 (Crispact®); Crispact® is a probiotic food supplement containing Lactobacillus crispatus M247.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HR-HPV Clearance Rate	Percentage of participants in whom HR-HPV infection is no longer detectable, as assessed by an HPV-DNA test.	Baseline to 4 months post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modifications in Vaginal Microbiota	Changes in the composition of the vaginal microbiota, including the abundance of Lactobacillus species (especially Lactobacillus crispatus) and microbiota diversity indices, as assessed by Next-Generation Sequencing of the 16S ribosomal RNA gene (NGS 16S) sequencing.	Baseline to 4 months post-intervention.
Microbiota Characteristics Favoring HR-HPV Infection or Clearance	Identification of vaginal microbiota profiles (e.g., CST-I (Community State Type-I) to CST-IV (Community State Type-IV) distribution) associated with HR-HPV persistence or clearance, as determined by NGS 16S sequencing	Baseline to 4 months post-intervention.
Cervical Cytology Normalization	Proportion of participants with normalization of cervical cytology results, transitioning from ASC-US (Atypical Squamous Cells of Undetermined Significance) or LSIL (Low-Grade Squamous Intraepithelial Lesion) to normal cytology, as determined by Papanicolaou (Pap) test analysis.	Baseline to 4 months post-intervention.
Number of patients reporting side effects to probiotic Crispact® intake	Number and type of adverse events reported, including gastrointestinal symptoms, allergic reactions, or other health concerns, as recorded in participant safety logs.	From baseline to 4 months post-intervention.

Collaborators and Investigators

• Sponsor: Liaquat University of Medical & Health Sciences
• Collaborators: Università degli Studi dell'Insubria

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2022
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): December 30, 2024

Study Registration Dates

• First Submitted: January 25, 2025
• First Submitted That Met QC Criteria: January 25, 2025
• First Posted (Actual): January 31, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Tumor Virus Infections; Infections; Communicable Diseases; Papillomavirus Infections
• Other Study ID Numbers: Protocol n° 774/18.10.2021/AK

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