Clinical trial NCT03748017: The Probiotic for Oral Health (PRO Health) Study
Official title: The Probiotic for Oral Health (PRO Health) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Oral Microbiome
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Renew Life Formulas Inc
First posted: 2018-11-20
Enrollment: 26
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be enrolled and randomized, receiving either a streptococcus-containing probiotic supplement or a placebo-control supplement.
Primary purpose: BASIC_SCIENCE

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Oral Streptococci levels in adults at 22 days - difference between S. Salivarius and placebo
timeFrame: 22 Days
Secondary outcomes:
measure: Oral Streptococcus levels
timeFrame: Change from baseline, days 10, 14, 22, 28, 36
measure: Oral microbiome
timeFrame: Change from baseline, days 10, 14, 22, 28, 36
measure: Number of stools per day
timeFrame: Change from baseline, days 10, 14, 22, 28, 36
measure: Changes in stool consistency
timeFrame: Change from baseline, days 10, 14, 22, 28, 36
measure: Changes in stool firmness
timeFrame: Change from baseline, days 10, 14, 22, 28, 36
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California, Davis
state: California
Study officials:
References:
citation: Horz HP, Meinelt A, Houben B, Conrads G. Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction. Oral Microbiol Immunol. 2007 Apr;22(2):126-30. doi: 10.1111/j.1399-302X.2007.00334.x.
citation: Upton M, Tagg JR, Wescombe P, Jenkinson HF. Intra- and interspecies signaling between Streptococcus salivarius and Streptococcus pyogenes mediated by SalA and SalA1 lantibiotic peptides. J Bacteriol. 2001 Jul;183(13):3931-8. doi: 10.1128/JB.183.13.3931-3938.2001.
citation: Ross KF, Ronson CW, Tagg JR. Isolation and characterization of the lantibiotic salivaricin A and its structural gene salA from Streptococcus salivarius 20P3. Appl Environ Microbiol. 1993 Jul;59(7):2014-21. doi: 10.1128/aem.59.7.2014-2021.1993.
citation: Cosseau C, Devine DA, Dullaghan E, Gardy JL, Chikatamarla A, Gellatly S, Yu LL, Pistolic J, Falsafi R, Tagg J, Hancock RE. The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun. 2008 Sep;76(9):4163-75. doi: 10.1128/IAI.00188-08. Epub 2008 Jul 14.
citation: Di Pierro F, Adami T, Rapacioli G, Giardini N, Streitberger C. Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults. Expert Opin Biol Ther. 2013 Mar;13(3):339-43. doi: 10.1517/14712598.2013.758711. Epub 2013 Jan 4.
citation: Di Pierro F, Colombo M, Zanvit A, Rottoli AS. Positive clinical outcomes derived from using Streptococcus salivarius K12 to prevent streptococcal pharyngotonsillitis in children: a pilot investigation. Drug Healthc Patient Saf. 2016 Nov 21;8:77-81. doi: 10.2147/DHPS.S117214. eCollection 2016.
citation: Di Pierro F, Donato G, Fomia F, Adami T, Careddu D, Cassandro C, Albera R. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media. Int J Gen Med. 2012;5:991-7. doi: 10.2147/IJGM.S38859. Epub 2012 Nov 30.
citation: Di Pierro F, Colombo M, Giuliani MG, Danza ML, Basile I, Bollani T, Conti AM, Zanvit A, Rottoli AS. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016 Nov;20(21):4601-4606.
citation: Burton JP, Chilcott CN, Tagg JR. The rationale and potential for the reduction of oral malodour using Streptococcus salivarius probiotics. Oral Dis. 2005;11 Suppl 1:29-31. doi: 10.1111/j.1601-0825.2005.01084.x.
citation: Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR. A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol. 2006 Apr;100(4):754-64. doi: 10.1111/j.1365-2672.2006.02837.x.
citation: Bourdichon F, Casaregola S, Farrokh C, Frisvad JC, Gerds ML, Hammes WP, Harnett J, Huys G, Laulund S, Ouwehand A, Powell IB, Prajapati JB, Seto Y, Ter Schure E, Van Boven A, Vankerckhoven V, Zgoda A, Tuijtelaars S, Hansen EB. Food fermentations: microorganisms with technological beneficial use. Int J Food Microbiol. 2012 Mar 15;154(3):87-97. doi: 10.1016/j.ijfoodmicro.2011.12.030. Epub 2011 Dec 31.
citation: Authority, E.F.S., Introduction of a Qualified Presumption of Safety (QPS) approach for assessment of selected microorganisms referred to EFSA-Opinion of the Scientific Committee. EFSA Journal, 2007. 5(12): p. 587.
citation: Mogensen, G., et al., Inventory of microoganisms with a documented history of use in food. 2002.