Lactobacillus Lozenges as Preventative Care in Low-grade Dysplasia

Study Overview
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Brief Summary
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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.

Official Title
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Lactobacillus Lozenges as Preventative Care in Low-grade Dysplasia

Conditions
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Low-grade Oral Dysplasia

Intervention / Treatment
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* Biological: Probiotic oral lozenges
* Other: Standard of care for oral dysplasia


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic lozenges<br>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<br>* 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.<br>* Other names: FLORASSIST® Oral Hygiene lozenges;|
| Active Comparator: Standard of care for oral dysplasia<br>Participants in this arm will receive oral dysplasia standard of care. | Other: Standard of care for oral dysplasia<br>* Oral dysplasia standard of care includes clinical surveillance and risk factor reduction (such as smoking cessation).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotic lozenge, Oral cavity squamous cell carcinoma, Oral microbiome