A Short, Open, Phase 0 Study to Demonstrate the Viability of the Lozenge Dosage Form to Deliver SALI-10 Oral Probiotics
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Changes in microbiome composition in the oral cavity
研究概览
简要总结
Gingivitis is an oral disease condition affecting 50% to 90% of adults globally. 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 shifts from gram-positive health-associated bacteria, to gram-negative disease associated species. This shift triggers inflammatory responses, leading to tissue damage and, in some cases, progression to periodontitis.
A promising area of oral health is treating the oral cavity with gram-positive probiotics to improve oral health. One promising candidate is S. salivarius SALI-10. Typically oral probiotics are dosed to the oral cavity using lozenges. This study is a pre-clinical Phase 0 trial to determine is a lozenge is a viable dosage form for the delivery of salivarius SALI-10 oral probiotics.
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.
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. For example, 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 have an induced neutropenia by chemical induction with antimitotic agents such as cyclophosamide invariably develop periodontitis. Likewise, studies in KO 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 a highly orchestrated expression of select 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.
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.
A recent study on human experimental gingivitis identified three distinct host response phenotypes-high, low, and slow responders-based on clinical, inflammatory, and microbial parameters:
High Responders: Rapid plaque accumulation accompanied by a significant increase in gram-negative periopathogens and elevated inflammatory markers, such as interleukin-1β (IL-1β).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •Non-smokers
- •Fluent in English
排除标准
- •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.
- •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.
- •History of periodontal disease.
- •History of systemic inflammatory or immune conditions
- •Pregnant or nursing women.
- •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;
- •Use of any concomitant medication.
研究组 & 干预措施
Receives Probiotic Lozenge
This study is an open-label, single-arm, exploratory pilot study to be completed over 7 days with 8-10 participants. Participants will self-administer one lozenge containing S. salivarius SALI-10 (10 billion CFU/lozenge) each night after brushing and before bed. Every participant will be given 7 SALI-10 lozenges.
- The aim of this study is to determine the short-term ability of the Streptococcus salivarius SALI-10 lozenges delivery system to modify the human oral microbiome composition and Oral Inflammatory Load (OIL). Specifically, the investigators aim to:
- Assess the change in salivary levels of periodontal-disease-associated bacteria (e.g., P. gingivalis, T. forsythia, T. denticola, and P. micra).
- Determine the change in beneficial bacteria levels (e.g., S. salivarius, S. parasanguinis).
- Evaluate the change in Oral Inflammatory Load (OIL) by measuring oral neutrophil counts.
- To monitor the short-term adherence of the 8-10 participants to the clinical protocol.
干预措施: Salivarius SALI-10 (Dietary Supplement)
结局指标
主要结局
Changes in microbiome composition in the oral cavity
时间窗: From enrollment to the end of treatment at 7 days
* Assess the change in salivary levels of periodontal-disease-associated bacteria (e.g., P. gingivalis, T. forsythia, T. denticola, and P. micra). * Determine the change in beneficial bacteria levels (e.g., S. salivarius, S. parasanguinis).
Change in Oral Inflammatory Load (OIL)
时间窗: Baseline (day 0) and day 7
Oral inflammatory load (OIL) is measured via oral neutrophil count in oral rinse samples (oPMN). Post-transplantation values (Day 7) are normalized to each participant's baseline (Day 0) value to evaluate the change in OIL. For normalization, each participant's baseline OIL was set to 1 by dividing the baseline neutrophil count by itself. Post-transplantation OIL values were then divided by the participants baseline to calculate fold change.
Change in SALI-10 Colonization Levels
时间窗: Baseline (day 0) and day 7
Quantification of SALI-10 colonization using qPCR targeting the srnA2 gene. Samples were collected at baseline (Day 0) and post-transplantation (Day 7). The srnA2 gene encodes for phosphorylated lantibiotic synthesized by S.salivarius SALI-10
Changes in the Relative Abundance of P. Gingivalis
时间窗: baseline (day 0) and day 7
Evaluation of pathogen suppression by quantifying the relative gene abundance of periodontal-disease-associated taxa (e.x. P. gingivalis, T. forsythia, P. micra and F. nucleatum) via qPCR. Relative gene abundance is expressed as the proportion of target bacterial 16s rRNA gene copies relative to the total bacterial 16s rRNA gene copies per mL. The measure reports the actual proportion at baseline and at day 7.
Changes in the Relative Abundance of T. Forsythia
时间窗: Baseline (day 0) and day 7
Evaluation of pathogen suppression by quantifying the relative gene abundance of periodontal-disease-associated taxa (e.x. P. gingivalis, T. forsythia, P. micra and F. nucleatum) via qPCR. Relative gene abundance is expressed as the proportion of target bacterial 16s rRNA gene copies relative to the total bacterial 16s rRNA gene copies per mL. The measure reports the actual proportion at baseline and at day 7.
Changes in the Relative Abundance of P. Micra
时间窗: Baseline (day 0) and day 7
Evaluation of pathogen suppression by quantifying the relative gene abundance of periodontal-disease-associated taxa (e.x. P. gingivalis, T. forsythia, P. micra and F. nucleatum) via qPCR. Relative gene abundance is expressed as the proportion of target bacterial 16s rRNA gene copies relative to the total bacterial 16s rRNA gene copies per mL. The measure reports the actual proportion at baseline and at day 7.
Changes in the Relative Abundance of F. Nucleatum
时间窗: Baseline (day 0) and day 7
Evaluation of pathogen suppression by quantifying the relative gene abundance of periodontal-disease-associated taxa (e.x. P. gingivalis, T. forsythia, P. micra and F. nucleatum) via qPCR. Relative gene abundance is expressed as the proportion of target bacterial 16s rRNA gene copies relative to the total bacterial 16s rRNA gene copies per mL. The measure reports the actual proportion at baseline and at day 7.
次要结局
- Oral Inflammatory Load(From enrollment to the end of treatment at 7 days.)
研究者
Michael Glogauer
Principal Investigator
Ostia Sciences