The Probiotic for Oral Health (PRO Health) Study

Study Overview
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Brief Summary
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The PRO Health Study is a single-center, prospective, double-blind, randomized, placebo-controlled trial of streptococcus-containing supplementation in healthy adults.

Detailed Description
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Upon enrollment, healthy adults will enter a 1-week lead-in period which serves as an opportunity to collect baseline saliva samples and complete daily logs. Subjects that meet eligibility criteria on Day 7 will be randomized into 1 of 2 groups, receiving either a placebo-control or a streptococcus-containing probiotic supplement. Supplementation will begin on Day 8 and will continue for a total of 14 consecutive days. Participants will be observed for an additional 2 weeks following cessation of supplementation. The total duration of the study will be approximately 5 weeks. Saliva samples will be collected on 7 occasions and participants will be asked to complete questionnaires and daily diet and health logs throughout the course of the study.

Official Title
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The Probiotic for Oral Health (PRO Health) Study

Conditions
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Oral Microbiome

Intervention / Treatment
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* Dietary Supplement: Placebo-Control Supplement
* Dietary Supplement: Streptococcus-Containing Probiotic Supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults; Age 21-45 years of age; BMI between 18-30; No history of infectious disease; heart, metabolic, autoimmune endocrine, liver, or kidney diseases; GI related conditions such as malabsorption disease, Crohn's disease, colitis, inflammatory bowel disease; Type 1 or 2 diabetes mellitus, any type of cancer, heart disease; Practices good oral hygiene according to the American Dental Association with brushing teeth between 1-2 times per day; Willingness to only use the study toothpaste to brush or clean teeth and refrain from using any other oral-care products such as other toothpaste, mouthwash, rinses and breath-sprays during the five-week study period; Willingness to limit consumption of raw onions or garlic and fermented foods such as sauerkraut, pickles, miso, and kimchi during the five-week study period; Non-alcohol consumers or those who consume alcohol in moderation defined as having up to 1 drink per day for women and up to 2 drinks per day for men; Willingness to avoid binge drinking during the study period defined by the Centers for Disease Control and Prevention as: This pattern of drinking usually corresponds to 5 or more drinks on a single occasion for men or 4 or more drinks on a single occasion for women, generally within about 2 hours; Willingness to refrain from drinking any alcohol within 24 hours of each saliva sample collection; Willingness to refrain from using illicit drugs during the five-week study; Willingness to refrain from using tobacco (smoking or chewing) or smoking marijuana during the five-week study period; Willingness to refrain from intake of probiotics, kombucha, or yogurt during the five-week study period; Willingness to refrain from consuming more than 1 package of sugary candy and from chewing more than 1 package of chewing gum during the five-week study period; Willingness to refrain from having any non-emergency, elective oral surgeries, dental procedures or dental teeth cleanings during the five-week study period. Exclusion Criteria: Currently pregnant or plans to become pregnant several weeks prior to enrollment and during the five-week study period; History of periodontal disease, or gingivitis; Dental trauma or injury to the teeth and/or periodontium (gums, periodontal ligament, alveolar bone), and nearby soft tissues such as the lips, tongue within the past 4 weeks; Any oral surgery or intensive procedures made to the oral cavity (such as fillings, wisdom tooth extraction, root canal, dental implants, etc.) within the past 4 weeks; Routine dental cleaning within the past 4 weeks; Use of probiotics, kombucha, or yogurt/kefir within the past 7 days of enrollment; Use of probiotics containing S. salivarius within the past 8 weeks of enrollment; Use of oral or IV antibiotics within the past 8 weeks of enrollment; Consumption of more than one package of sugary candy (hard candy, gummy candy, mints, etc.) per day; Use of more than one package of chewing gum (sugary or sugarless) per day; Use of mouthwashes, mouth-rinses or breath-sprays more than three times per day; Current tobacco (smoking or chewing) or E-cigarette users or individuals who quit using less than one year before enrolling in the study; Frequent marijuana smoking or vaping, or use of other illicit drugs (must be no more than 12 times within the past year and no more than once per month); Marijuana smoking or vaping or use of other illicit drugs within the past 4 weeks; Excessive alcohol drinkers: For men, heavy drinking is typically defined as consuming 15 drinks or more per week. For women, heavy drinking is typically defined as consuming 8 drinks or more per week; Individuals who live within the same household or who are in intimate relationships with current or past study participants (to avoid horizontal transfer of the oral microbiome); Anyone the investigator feels isn't an applicable participant.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be enrolled and randomized, receiving either a streptococcus-containing probiotic supplement or a placebo-control supplement.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-Control Supplement<br>12 participants will receive a placebo-control supplement per daily oral feeding. | Dietary Supplement: Placebo-Control Supplement<br>* A once-daily oral dose of the placebo-control supplement will be consumed by adults for 14 consecutive days.<br>|
| Active Comparator: Streptococcus-Containing Probiotic Supplement<br>12 participants will receive a powdered probiotic containing 7.77 billion colony-forming units (CFU) of L. acidophilus, 8.25 billion CFU of B. lactis, and 2 billion CFU of S. salivarius bacteriocin-like inhibitory substance (BLIS) K12 per daily oral feeding. | Dietary Supplement: Streptococcus-Containing Probiotic Supplement<br>* A once-daily oral dose of the streptococcus-containing probiotic supplement will be consumed by adults for 14 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral Streptococci levels in adults at 22 days - difference between S. Salivarius and placebo | The difference in levels of oral Streptococci between a streptococcus-containing probiotic supplement (e.g., S. salivarius K12) and placebo-control supplement on Day 22. | 22 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral Streptococcus levels | The difference in levels of Streptococci upon intake of a streptococcus-containing probiotic supplement (e.g., S. salivarius K12) before, during and after the intervention compared with a placebo-control supplement. | Change from baseline, days 10, 14, 22, 28, 36 | 
| Oral microbiome | The difference in the salivary microbiome before, during and after intake of a streptococcus-containing probiotic supplement (e.g., S. salivarius K12) and placebo-control supplement. | Change from baseline, days 10, 14, 22, 28, 36 | 
| Number of stools per day | The relationship between supplementation and number of stools per day. | Change from baseline, days 10, 14, 22, 28, 36 | 
| Changes in stool consistency | The relationship between supplementation and number of stools per day, rated using the Bristol Stool Scale. | Change from baseline, days 10, 14, 22, 28, 36 | 
| Changes in stool firmness | The relationship between supplementation and number of stools per day, rated using a continuous scale of 1 to 10 (1 = extremely watery, almost entirely liquid to 10 = extremely hard, difficult to pass). | Change from baseline, days 10, 14, 22, 28, 36 |