A Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy SALI-10 Oral Probiotics in Experimental Gingivitis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Mean change in percentage of sites with bleeding on probing (BOP)
研究概览
简要总结
Gingivitis is among the most prevalent oral diseases worldwide, affecting an estimated 50-90% of adults. It is a reversible condition primarily caused by microbial plaque accumulation on teeth and gingival surfaces, which triggers inflammation. Standard care emphasizes plaque reduction through oral hygiene, and research shows gingivitis can be reversed once hygiene resumes. The classic experimental gingivitis (EG) model developed in 1965 by Löe and Silness demonstrated the direct link between plaque buildup and gingival inflammation, further confirming that gingival health can be restored after resuming proper care.
Microbial ecology shifts are central to gingivitis pathogenesis. In health, the oral microbiome is dominated by gram-positive Streptococcus species. With plaque accumulation, microbial communities transition to gram-negative periopathogens such as Porphyromonas, Tannerella, Treponema, and Prevotella. This dysbiosis provokes heightened inflammation, tissue damage, and, in susceptible individuals, progression to periodontitis. Individual variability in the inflammatory response has been associated with differences in the presence and activity of beneficial streptococci. Certain strains of Streptococcus salivarius produce lantibiotics called salivaricins-polycyclic antimicrobial peptides containing lanthionine residues. Salivaricins inhibit oral pathogens and have been investigated for their antimicrobial and probiotic properties, particularly in the context of rising antibiotic resistance. Probiotic S. salivarius strains isolated from healthy individuals have demonstrated safety and antimicrobial potential in previous studies, supporting their use in preventing oral and respiratory infections.
A strain of S. salivarius designated SALI-10 produces a lantibiotic, Salivaricin 10, and is being evaluated as a candidate for gingivitis prevention. This strain is hypothesized to (1) help stabilize populations of beneficial streptococci during plaque accumulation, (2) competitively inhibit periopathogens such as Porphyromonas and Prevotella, and (3) suppress the dysbiotic shift toward gram-negative dominance. By contributing to microbial balance and reducing inflammatory triggers, SALI-10 may support resilient host-microbe interactions associated with gingival health. This approach may offer a dual antimicrobial and microbiome-stabilizing strategy with relevance to gingivitis management and longer-term periodontal health.
详细描述
Gingivitis is an oral disease condition affecting 50% to 90% of adults globally. The gingivitis pathology can be reversed by reduction or removal of microbial plaque that accumulates on hard and soft tissues and is considered standard of care in the industry. Regular oral hygiene in combination with therapeutics that delivers an anti-microbial benefit is thought to mitigate the onset of gingivitis. However, testing therapeutics for prophylaxis benefit to mitigate development of gingivitis has not been fully examined.
The classical model of experimental gingivitis (EG) was developed in 1965 by Loe and Silness who convincingly demonstrated the causative relationship between the accumulation of dental plaque and the development of clinically evident gingivitis in healthy young adults abstaining from all oral hygiene practices for a 21-day period. Furthermore, on resuming customary oral hygiene practices, all subjects demonstrated a return to gingival health. Understanding how participants returned quickly to gingival health aligns with the current understanding that the clinically healthy state is an active and dynamic process.
Neutrophils, a type of white blood cell (leukocyte), represent a key component of the innate defence system that protects periodontal tissue from both gingivitis and periodontitis. Not only are they the first line of cellular defence, but they are among the most abundant leukocytes within the periodontal tissues. Gingivitis is associated with a significant increase in the number of neutrophils that migrate to periodontal tissue. In contrast, individuals with too few neutrophils brought about by either congenital deficiencies in neutrophil numbers or transit (LAD 1 and 2), or those with induced neutropenia by chemical induction with antimitotic agents such as cyclophosphamide, invariably develop periodontitis. Likewise, studies in knockout mice that are defective in neutrophil transit also develop periodontitis. Consistent with the key contribution of neutrophils to both gingivitis and periodontitis, neutrophil transit to gingival tissue is highly regulated. The periodontium contains innate host defense mediators that facilitate the transit of neutrophils from the highly vascularized gingival tissue to the gingival crevice, where they form a "wall" between the host tissue and the dental plaque biofilm.
However, the prolonged presence of neutrophils in gingival tissue is not tolerated in the healthy state. The failure to downregulate neutrophil transit results in an increase in neutrophil numbers in gingival tissue and a significant increase in periodontal bone loss. Therefore, neutrophil homing to the gingival crevice is highly regulated such that under conditions of periodontal health the appropriate amount of neutrophils are present to maintain control of dental plaque bacterial growth and yet not elicit tissue damage. Evaluation of oral and blood neutrophils during experimental gingivitis has shown that people with uniquely high inflammatory response have an exaggerated polymorphonuclear neutrophil response both in the oral cavity and in the blood.
Gingivitis is a reversible inflammatory condition caused by the accumulation of dental plaque and the associated disruption of the host-microbial homeostasis. During gingivitis, the microbial community transitions from being dominated by gram-positive health-associated bacteria, such as Streptococcus species, to gram-negative periopathogens, including species of the genera Porphyromonas, Tannerella, Treponema and Prevotella. This dysbiotic shift triggers inflammatory responses, leading to tissue damage and, in some cases, progression to periodontitis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female volunteers aged 18-70 years
- •In good general health, ASA I
- •No clinical signs of gingival inflammation at >90% of sites observed
- •Absence of Periodontal Pockets, Probing Depth (PD) < 3.0 mm on all teeth/site
- •Absence of Clinical Attachment Loss (CAL) = 0 mm
- •No periodontal disease history
- •Have at least 20 gradeable teeth
- •Non-smokers
- •Fluent in English
- •For study participants of childbearing potential, both men and women, at least one of the following birth control measures must be used: abstinence, hormonal birth control (oral, injectable, transdermal, intra-vaginal), intrauterine devices, confirmed successful vasectomy, or condoms.
排除标准
- •Presence of orthodontic bands.
- •Presence of partial or full dentures.
- •Tumour(s) of the soft or the hard tissues of the oral cavity.
- •Cavitated carious lesions requiring immediate restorative treatment.
- •History of allergy to a consumer or personal care products or dentifrice ingredients as determined by the dental profession monitoring the study.
- •Participation in any other clinical study or test panel within one month before entering the study.
- •Medical condition which requires pre-medication before dental visits/procedures
- •Current use of anti-inflammatory, antibiotics, or antimicrobial drugs or within the last 30 days of enrolment.
- •History of periodontal disease.
- •History of systemic inflammatory, immune conditions and immunocompromised conditions
- •Pregnant or nursing women or those planning to get pregnant
- •Use of tobacco products.
- •Long-term antibiotic or anti-inflammatory therapy.
- •Medication or Natural Health Products (NHPs) that could affect the gingiva like calcium channel blockers, anti-epileptic therapy etc.
- •Medical condition or any current usage of medication that the investigator considers may compromise the study participant's safety as well as the quality of the study results
- •Allergy to any of the following ingredients: Streptococcus Salivarius, Sorbitol, Isomalt, Calcium phosphate dibasic, Potato starch, Mint, Glyceryl dibehenate, Stevia, Maltodextrin
- •Use of other probiotics
- •Taking anticoagulant medications and those suffering from blood and bleeding disorders
- •Recently experienced or will be experiencing dental, oral or any type of surgery.
- •Use of anti-plaque/ anti-gingivitis products
- •Presence of active infections
- •Participants who are experiencing nausea, fever, vomiting, bloody diarrhoea or severe abdominal pain.
- •Use of any antibiotics.
结局指标
主要结局
Mean change in percentage of sites with bleeding on probing (BOP)
时间窗: Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).
Bleeding on probing (BOP) will be assessed at six sites per tooth using a UNC-15 periodontal probe. The proportion of bleeding sites (% of total sites) will be calculated for each participant. Group mean ± SD change from baseline will be reported. Scale: 0-100 %; lower values = less gingival inflammation.
次要结局
- Change in oral neutrophil (oPMN) count per 10 mL unstimulated saliva(Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).)
- Change in concentration of cytokines (IL-1β, IL-6, MMP-8) in gingival crevicular fluid (pg/mL)(Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).)
- Change in relative abundance of periodontal and commensal bacteria measured by quantitative PCR and shotgun metagenomics(Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).)
- Change in concentration of volatile sulfur compounds (VSCs) in exhaled air measured by Halimeter (ppb)(Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).)
- Change in mean Gingival Index (GI) score(Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).)
- Change in mean Plaque Index (PI) score(Baseline; Weeks 1 and 2 (pre-induction); Weeks 3 - 5 (induction phase - no-brushing); Weeks 6 and 7 (resolution phase).)