Evaluation of the Safety and Efficacy of SALI-10 Probiotic Lozenges

NCT07508839 | Not Yet Recruiting

• 1 other identifier: OstiaOralHealth
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Gingivitis is among the most common oral conditions, affecting 50-90% of adults globally. It is a reversible inflammatory disease triggered primarily by the accumulation of microbial plaque on teeth and gingival tissues. Standard treatment involves plaque reduction and maintenance of oral hygiene, often supplemented with antimicrobial therapeutics to prevent disease progression. While plaque control remains the cornerstone of prevention, emerging research points to certain beneficial microbes that may protect gingival health. Notably, Streptococcus species have been associated with both antimicrobial and anti-inflammatory activities, suggesting their potential as oral probiotics. Recent investigations have focused on a novel strain, Streptococcus salivarius SALI-10, which produces a lantibiotic called Salivaricin 10. This peptide exhibits unique immunomodulatory properties. In murine models, Salivaricin 10 was shown to enhance neutrophil recruitment and activity while directing monocytes toward the M2 pro-resolution macrophage phenotype, a cell population integral to tissue repair and late-stage wound healing. Such effects highlight the potential of SALI-10 to reduce gingival inflammation while fostering microbial balance. The concept of employing S. salivarius strains in oral health is not entirely new. Other variants isolated from the oral cavities of healthy individuals produce lantibiotics with lanthionine or β-methyllanthionine residues that demonstrate antimicrobial effects against pathogens. Clinical investigations have explored these probiotic strains for halitosis, plaque control, and gingivitis, reporting safety and efficacy. Moreover, salivaricin-producing strains are considered valuable in the ongoing search for alternatives to conventional antibiotics in light of increasing resistance. Understanding the microbial ecology of gingivitis helps contextualize this therapeutic potential. In health, gram-positive bacteria, particularly Streptococcus species, dominate the oral microbiome. Gingivitis involves a shift toward gram-negative periopathogens such as Porphyromonas, Tannerella, Treponema, and Prevotella. This dysbiosis provokes an inflammatory cascade characterized by neutrophil infiltration, tissue damage, and, if unresolved, progression to periodontitis. A recent human experimental gingivitis study revealed distinct host response phenotypes. Participants retaining beneficial Streptococcus species, such as S. sanguinis and S. oralis, experienced reduced periopathogen emergence and milder inflammation. By contrast, participants who lost these protective bacteria demonstrated greater inflammatory severity, underscoring the critical role of Streptococcus persistence in oral homeostasis. Neutrophils, the most abundant immune cells in periodontal tissues, are central to this dynamic. Their numbers increase proportionally with gingivitis severity. Importantly, Health Canada has recently recognized salivary neutrophil activity as a valid biomarker for assessing inflammatory burden and risk of gingivitis or periodontal disease. This regulatory approval highlights the growing emphasis on immune function as both a diagnostic measure and therapeutic target in oral health. Against this backdrop, S. salivarius SALI-10 presents a compelling intervention strategy. Its hypothesized benefits include reducing inflammation via promotion of the M2 macrophage phenotype, suppressing periopathogen growth through competitive exclusion and Salivaricin 10 production, and mitigating halitosis by blocking volatile sulfur compound-producing bacteria. To evaluate these benefits, a proposed study design involves administering a twice-daily lozenge , one in the morning and one in the evening, after brushing a tongue scraping each containing 3 billion CFU of SALI-10 over a four-week period. In summary, gingivitis remains highly prevalent but reversible. Beyond traditional hygiene approaches, microbial therapeutics such as S. salivarius SALI-10 may offer a dual antimicrobial and anti-inflammatory benefit. By promoting immune resolution and reshaping the microbial community, SALI-10 could emerge as a novel probiotic strategy in maintaining oral health and addressing the limitations of conventional antimicrobial therapies.

Conditions

Gingivitis; Halitosis

Keywords

Oral Health; Probiotics

Outcome Measures

Primary Outcomes (3)

• Reduction of gingival inflammation between the probiotic and placebo groups determined by bleeding on probing (BOP)

  This study will assess the efficacy of SALI-10 in reducing gingival inflammation following administration of probiotic lozenges containing SALI-10 compared with a placebo lozenge. This will be measured using bleeding on probing, defined as bleeding observed in more than 10% of probing sites. Statistical analysis (e.g. Students t-test) will be conducted to compare the participants' data from baseline (day -21), start of intervention (day 0), completion of intervention (day 30), and the washout period (day 60), with significance at p≤ 0.05 across both the probiotic and placebo groups.

  81 days

• Reduction of gingival inflammation between the probiotic and placebo groups determined by oral inflammatory load

  This study will assess the efficacy of SALI-10 in reducing gingival inflammation following administration of probiotic lozenges containing SALI-10 compared to a placebo lozenge. This will be measured by oral inflammatory load, as defined by oral neutrophil (oPMN) counts. Statistical analysis (e.g. Students t-test) will be conducted to compare the participants' data from baseline (day -21), start of intervention (day 0), completion of intervention (day 30), and the washout period (day 60), with significance at p≤ 0.05 across both the probiotic and placebo groups.

  81 days

• Number of patients with treatment-related adverse events of twice-daily SALI-10 lozenge using an end of study questionnaire

  In this study, investigators will evaluate the safety and tolerability of a twice-daily SALI-10 lozenge use, one in the morning and one in the evening, after brushing and tongue scraping, over 4 weeks. To determine this, participants will be given an end-of-study questionnaire including parameters such as: How easy was it to use the lozenge as instructed? How was the taste of the lozenge (determined using a scale)? Did you experience any side effects (with listed side effects)? Statistical analysis (e.g. Students t-test) will be conducted to compare the participants' data with significance at p≤ 0.05 between the probiotic and placebo groups.

  81 days

Secondary Outcomes (2)

• Determine the probiotics impacts on halitosis through patient-reported outcomes using the HALT questionnaire

  81 days

• Determine the probiotics' impacts on halitosis through volatile sulfur compounds (VSC) in pbb

  81 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

This arm will receive lozenges without the active ingredient

Other: Placebo

SALI-10

ACTIVE COMPARATOR

This arm will receive lozenges containing the active ingredient (3B CFUs of SALI-10)

Dietary Supplement: 3B SALI-10 Lozenge

Interventions

3B SALI-10 Lozenge DIETARY_SUPPLEMENT

A lozenge containing 3B CFUs of the probiotic . S. salivarius SALI-10

SALI-10

Placebo OTHER

It is a placebo lozenge with no active ingredient.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female volunteers aged 18-70 years
• In good general health, ASA I
• Non-smokers
• Fluent in English
• For sexually active volunteers of childbearing potential, one of the following methods must be used to prevent pregnancy during the study by participants.
• Post-menopausal
• hormonal birth control (oral, injectable, transdermal, intra-vaginal) or intrauterine device must be in use at least 30 days prior to first study drug administration;
• barrier methods must be in use at least 14 days prior to study drug administration;
• that vasectomy on the male partner must be completed 3 months prior to first study drug administration;
• or in the alternative that a 0 sperm count for the male partner will suffice

You may not qualify if:

• Presence of orthodontic bands.
• Presence of partial removal dentures.
• Dental pain at time of screening.
• History of allergy to a consumer or personal care products or dentifrice ingredients as determined by the dental profession monitoring the study, or to any of the following: sorbitol, isomalt, dibasic calcium phosphate, potato or potato starch, mint or mint flavour, glyceryl dibehenate, steviol glycosides.
• Participation in any other clinical study or test panel within one month before entering the study.
• Current use of anti-inflammatory, antibiotics, or antimicrobial drugs or within the last 30 days of enrolment.
• Those taking anticoagulant medications and have blood and bleeding disorders
• Those who have recently experienced (past 30 days) or will be experiencing (next 90 days) dental, oral, or any type of surgery
• History of systemic inflammatory or immune conditions or immunocompromised conditions
• Pregnant or nursing women or those planning on getting pregnant.
• Use of tobacco products.
• Long-term antibiotic or anti-inflammatory therapy.
• Medical condition or any current usage of medication that the investigator considers may compromise the subject's safety as well as the quality of the study results (note, only Advil and Tylenol are allowed during the study for analgesia)
• Medication or Natural Health Products (NHPs) that could affect the gingiva like calcium channel blockers, anti-epileptic therapy etc.
• Participants who are experiencing nausea, fever, vomiting, bloody diarrhoea or severe abdominal pain.

Sponsors & Collaborators

• Ostia Sciences: lead

Study Sites (1)

OMGPerio

Hamilton, Ontario, L8N 1K4, Canada

Location

Related Publications (17)

• Yin L, Li X, Hou J. Macrophages in periodontitis: A dynamic shift between tissue destruction and repair. Jpn Dent Sci Rev. 2022 Nov;58:336-347. doi: 10.1016/j.jdsr.2022.10.002. Epub 2022 Oct 28.

  PMID: 36340583 BACKGROUND

• Tarasenko VD, Kozin IaB. [Work standards for the medical personnel of radiodiagnostic laboratories]. Med Radiol (Mosk). 1975 Feb;20(2):43-7. No abstract available. Russian.

  PMID: 1134231 BACKGROUND

• LOE H, SILNESS J. PERIODONTAL DISEASE IN PREGNANCY. I. PREVALENCE AND SEVERITY. Acta Odontol Scand. 1963 Dec;21:533-51. doi: 10.3109/00016356309011240. No abstract available.

  PMID: 14121956 BACKGROUND

• Loe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967 Nov-Dec;38(6):Suppl:610-6. doi: 10.1902/jop.1967.38.6.610. No abstract available.

  PMID: 5237684 BACKGROUND

• Li X, Fields FR, Ho M, Marshall-Hudson A, Gross R, Casser ME, Naito M. Safety assessment of Streptococcus salivarius DB-B5 as a probiotic candidate for oral health. Food Chem Toxicol. 2021 Jul;153:112277. doi: 10.1016/j.fct.2021.112277. Epub 2021 May 15.

  PMID: 34004226 BACKGROUND

• Lee YH, Shin SI, Hong JY. Investigation of volatile sulfur compound level and halitosis in patients with gingivitis and periodontitis. Sci Rep. 2023 Aug 14;13(1):13175. doi: 10.1038/s41598-023-40391-3.

  PMID: 37580412 BACKGROUND

• Landzberg M, Doering H, Aboodi GM, Tenenbaum HC, Glogauer M. Quantifying oral inflammatory load: oral neutrophil counts in periodontal health and disease. J Periodontal Res. 2015 Jun;50(3):330-6. doi: 10.1111/jre.12211. Epub 2014 Jul 14.

  PMID: 25040400 BACKGROUND

• Kuninaka Y, Ishida Y, Ishigami A, Nosaka M, Matsuki J, Yasuda H, Kofuna A, Kimura A, Furukawa F, Kondo T. Macrophage polarity and wound age determination. Sci Rep. 2022 Nov 25;12(1):20327. doi: 10.1038/s41598-022-24577-9.

  PMID: 36434083 BACKGROUND

• Kerns KA, Bamashmous S, Hendrickson EL, Kotsakis GA, Leroux BG, Daubert DD, Roberts FA, Chen D, Trivedi HM, Darveau RP, McLean JS. Localized microbially induced inflammation influences distant healthy tissues in the human oral cavity. Proc Natl Acad Sci U S A. 2023 Oct 10;120(41):e2306020120. doi: 10.1073/pnas.2306020120. Epub 2023 Oct 2.

  PMID: 37782795 BACKGROUND

• Hirschfeld J. Neutrophil Subsets in Periodontal Health and Disease: A Mini Review. Front Immunol. 2020 Jan 8;10:3001. doi: 10.3389/fimmu.2019.03001. eCollection 2019.

  PMID: 31998301 BACKGROUND

• He L, Yang H, Chen Z, Ouyang X. The Effect of Streptococcus salivarius K12 on Halitosis: a Double-Blind, Randomized, Placebo-Controlled Trial. Probiotics Antimicrob Proteins. 2020 Dec;12(4):1321-1329. doi: 10.1007/s12602-020-09646-7.

  PMID: 32227309 BACKGROUND

• Briceag R, Caraiane A, Raftu G, Bratu ML, Buzatu R, Dehelean L, Bondrescu M, Bratosin F, Bumbu BA. Validation of the Romanian Version of the Halitosis Associated Life-Quality Test (HALT) in a Cross-Sectional Study among Young Adults. Healthcare (Basel). 2023 Sep 30;11(19):2660. doi: 10.3390/healthcare11192660.

  PMID: 37830697 BACKGROUND

• Berezow AB, Darveau RP. Microbial shift and periodontitis. Periodontol 2000. 2011 Feb;55(1):36-47. doi: 10.1111/j.1600-0757.2010.00350.x. No abstract available.

  PMID: 21134227 BACKGROUND

• Barbour A, Wescombe P, Smith L. Evolution of Lantibiotic Salivaricins: New Weapons to Fight Infectious Diseases. Trends Microbiol. 2020 Jul;28(7):578-593. doi: 10.1016/j.tim.2020.03.001. Epub 2020 Apr 6.

  PMID: 32544444 BACKGROUND

• Barbour A, Smith L, Oveisi M, Williams M, Huang RC, Marks C, Fine N, Sun C, Younesi F, Zargaran S, Orugunty R, Horvath TD, Haidacher SJ, Haag AM, Sabharwal A, Hinz B, Glogauer M. Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome. Proc Natl Acad Sci U S A. 2023 May 30;120(22):e2219392120. doi: 10.1073/pnas.2219392120. Epub 2023 May 22.

  PMID: 37216534 BACKGROUND

• Babina K, Salikhova D, Doroshina V, Makeeva I, Zaytsev A, Uvarichev M, Polyakova M, Novozhilova N. Antigingivitis and Antiplaque Effects of Oral Probiotic Containing the Streptococcus salivarius M18 Strain: A Randomized Clinical Trial. Nutrients. 2023 Sep 6;15(18):3882. doi: 10.3390/nu15183882.

  PMID: 37764667 BACKGROUND

• Albandar JM, Rams TE. Global epidemiology of periodontal diseases: an overview. Periodontol 2000. 2002;29:7-10. doi: 10.1034/j.1600-0757.2002.290101.x. No abstract available.

  PMID: 12102700 BACKGROUND

MeSH Terms

Conditions

Gingivitis; Halitosis

Condition Hierarchy (Ancestors)

Infections; Gingival Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Dr. Alon Borenstein, MDM, M.Sc Periodontology

  OMGPerio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Kwiecinski, P.Eng, M.Sc Physics

CONTACT

1-613-513-4413; Mark@PMKengineering.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is a randomized, double blind, placebo-controlled clinical trial enrolling 60 participants with gingivitis (BOP above 10%). Participants will be randomly assigned in a 1:1 allocation ratio to receive either SALI-10 probiotic lozenges or placebo lozenges. Randomization will be performed by an independent third party (PMK Federal Regulatory Consultants Ltd.) using a computer-generated randomized sequence. The participants, investigators, and dental clinicians/outcome assessors are all blinded to group allocation. The probiotic and placebo lozenges will be identical in appearance, taste, and packaging to maintain blinding. The randomized code will be held by PMK Federal Regulatory Consultants Ltd. and will not be released until completion of data analysis, unless unblinding is required for safety reasons. Participants will self-administer a twice-daily lozenge, one in the morning and one in the evening, after brushing and tongue scraping.

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: April 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2025-09

Locations

CA (1)