Lactobacillus Lozenges as Preventative Care in Low-grade Dysplasia

There are limited evidence-based management options for patients with low-grade oral dysplasia. Despite the risk of malignant transformation, management is frequently limited to risk factor reduction (such as smoking cessation) and clinical surveillance. An intervention for low-grade oral dysplasia which could induce regression or decrease rates of malignant transformation has the potential to be a valuable preventative tool to reduce rates of oral cancer.

The investigators will conduct a randomized clinical trial to investigate if the administration of a probiotic lozenge to patients with low-grade oral dysplasia result in decreased peri-tumoral inflammation as evidenced by impacts on populations of tumor-associated macrophages and tumor-infiltrating lymphocytes, and decreased dysbiosis at the disease site compared with the contralateral normal site. The investigators hypothesize that these changes may increase the rate of clinical regression of these lesions.

Study Overview

• Status: Withdrawn
• Conditions: Low-grade Oral Dysplasia
• Intervention / Treatment: Biological: Probiotic oral lozenges; Other: Standard of care for oral dysplasia

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Presence of biopsy-proven low-grade or mild oral dysplasia

Exclusion Criteria:

• Active oral cavity malignancy
• Active oral cavity high grade dysplasia
• Currently undergoing chemotherapy or immunotherapy, or have used these agents within the prior 6 months
• History of external beam radiation therapy to the head and neck area
• Diagnosis of HIV with decreased CD4 count and/or detectable viral load
• Current use of systemic or orally absorbed steroids
• Patient undergoing stem cell transplantation
• Patients taking anti-rejection medication after stem cell or solid organ transplantation
• Patients using injectable immunosuppressive drugs for autoimmune disease
• Pregnant or nursing women
• Patients who are hospitalized
• Patients with a heart valve abnormalities or a history of valve replacement or endocarditis
• Patients with active severe acute intestinal disease (active bowel leak, acute abdomen, active colitis) or a history of short bowel syndrome

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic lozenges; Participants in this arm will be be instructed to take a lozenge daily for 6 weeks. They will also receive oral dysplasia standard of care.	Biological: Probiotic oral lozenges; Participants in this arm will be be instructed to take a lozenge daily for 6 weeks. They will also receive oral dysplasia standard of care.; Other Names: FLORASSIST® Oral Hygiene lozenges
Active Comparator: Standard of care for oral dysplasia; Participants in this arm will receive oral dysplasia standard of care.	Other: Standard of care for oral dysplasia; Oral dysplasia standard of care includes clinical surveillance and risk factor reduction (such as smoking cessation).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical regression of dysplastic lesion	This outcome will be assessed using blinded review of clinical photographs and measurements of the lesions to determine if the lesion has regressed, remained the same or progressed since baseline.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome at the lesion site	The microbiome at the lesion site will be compared with the contralateral normal tissue to determine whether the dysbiotic oral microbiome will show a reduction in the abundance of oral cancer-associated microbial populations after treatment with the probiotic lozenge, and whether any changes seen will persist after cessation of treatment. The analysis of the microbiology specimens will include 16s sequencing and analysis.	baseline, 6 weeks, 12 weeks
Change in peri-tumoral inflammation	Peri-tumoral inflammation will be assessed by analyzing populations of tumor-associated macrophages and tumor-infiltrating lymphocytes in the biopsy performed after 6 weeks of treatment compared to the pre-treatment biopsy.	baseline, 6 weeks
Oral dysplasia lesions at 12 weeks	This outcome will be assessed using blinded review of clinical photographs and measurements of the lesions to determine if the lesion has regressed, remained the same or progressed.	12 weeks

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: University of Alabama at Birmingham
• Investigators: Principal Investigator: Heather Edwards, MD, Boston Medical Center, Otolaryngology

Study record dates

Study Major Dates

• Study Start (Estimated): April 29, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: December 10, 2022
• First Submitted That Met QC Criteria: January 22, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Oral microbiome; Probiotic lozenge; Oral cavity squamous cell carcinoma
• Additional Relevant MeSH Terms: Pathologic Processes; Hyperplasia
• Other Study ID Numbers: H-42906

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No