Oral-Spray Bacillus Spore Probiotics for Periodontal Disease Prevention and Supprotive Treatment in the Elderly

Официальное название

Evaluating Safety and Efficacy of Oral-Spray Bacillus Spore Probiotics (LiveSpo Smile CARE) in Preventing and Supporting the Treatment of Periodontal Diseases in Elderly in Hanoi

Обзор

Periodontal diseases are strongly associated with dysbiosis of the oral microbiome within the biofilm. Key pathogens, including Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, contribute to caries progression and periodontal inflammation. Given the limitations of antibiotic use and their potential side effects, probiotics represent a promising biological approach to restore microbial balance and support oral health. In this study, researchers propose that direct application of probiotic spray into the oral cavity is safe and effective in alleviating typical symptoms of periodontal disease, particularly by reducing pathogenic bacterial density. The objective of this study is to evaluate the safety and efficacy of a oral-spray Bacillus spore probiotics (LiveSpo Smile CARE), containing Bacillus subtilis ANA48 and Bacillus clausii ANA39 at a concentration of ≥ 1 billion CFU/mL x 20 mL formulation, for the prevention and supportive treatment of periodontal disease. Study Design: * Sample Size: 90 participants * Study Location: an elderly care center in Hanoi, Vietnam Intervention Description: A total of 90 eligible participants will be randomly assigned to two groups (n = 45 per group). * The Placebo Group will receive 0.9% NaCl physiological saline, spray twice daily (afternoon and evening), with two sprays per application at three sites (both dental arches and the front teeth), totaling six sprays per use, for four consecutive weeks. * The Smile Care Group will receive an oral-spray probiotics containing ≥ 1 billion CFU/mL × 20 mL of Bacillus subtilis and Bacillus clausii (LiveSpo Smile CARE), administered with the same dosage and frequency as the placebo group. All participants will receive blinded, coded spray bottles to ensure objectivity. Both groups will be instructed to use the same standardized toothpaste during the study period. Caregivers will monitor the health status of participants and record relevant information in their medical records. During the study, caregivers will be instructed not to provide any additional probiotic oral care products or the solution contains similar components. Study Duration: 12-18 months.

Подробное описание

According to the World Health Organization (WHO), severe oral disease is estimated to affect over 1 billion individuals worldwide. Studies have demonstrated that the prevalence of periodontal disease increases with age. In Vietnam, oral disease is a common oral health problem among the elderly, with a prevalence rate of approximately 91%. This includes 51.6% presenting with simple gingivitis and 39.4% with periodontitis. If left untreated, oral disease may lead to gingival inflammation, swelling, bleeding, and destruction of the supporting structures of the teeth, resulting in pain during mastication. In severe cases, it can cause tooth loss, systemic infections such as sepsis, and increase the long-term risk of systemic diseases including cardiovascular disease and diabetes.

Conventional treatment primarily focuses on the mechanical removal of dental plaque through tooth brushing and flossing. While these methods are effective in reducing gingival inflammation and bacterial load, they often fail to completely eliminate plaque, especially in interdental areas. Probiotics have shown promising potential as adjunctive therapy in the management of periodontal disease by restoring microbial balance, modulating host inflammatory responses, and reducing the levels of pathogenic bacteria.

The objective of this study is to evaluate the prevention and supportive therapeutic efficacy of a oral-spray Bacillus spore probiotics (LiveSpo Smile CARE) in alleviating typical symptoms of periodontal disease. Investigators will assess safety, clinical symptom improvement, and reduction in the oral pathogenic bacterial load in elderly participants after 7, 14, 28, and 42 days of using LiveSpo Smile CARE.

This will be a randomized, blind, placebo-controlled clinical trial. The trial will have 12-18 months of duration. Participants will be required to provide demographic data, oral health history, and information regarding prior antibiotic use. Upon providing written informed consent and meeting eligibility criteria, 90 participants will be enrolled and randomly assigned to two groups (n = 45 per group). The placebo group will receive a 0.9% NaCl physiological saline spray, while the intervention group ("Smile Care") will receive the oral-spray probiotics, LiveSpo Smile CARE.

-Primary outcomes

Changes in clinical symptoms (For example: Debris Index-Simplified \[DI-S\], Gingival Index \[GI\], Bleeding on Probing \[BOP\], Gingival Recession \[REC\], Probing Depth \[PD\], Clinical Attachment Level \[CAL\], Halitosis...) at day 28 vs. day 0.

-Secondary outcomes

Changes in cytokine levels (ELISA) and semi-quantification of bacterial pathogens (real-time PCR) in gingival crevicular fluid samples, collected at day 28 compared with day 0.

\- Expected outcomes Change in the oral microbiome composition at day 28 vs. day 0.

Presence of Bacillus subtilis ANA48 and Bacillus clausii ANA39 in gingival fluid will be assessed by real-time PCR at follow-up visits (days 7, 14, 28 and 42) compared with day 0, to confirm product use compliance.

Statistical analysis will be conducted using the chi-square test or Fisher's exact test for categorical variables, and t-test, Mann-Whitney test, or Wilcoxon test for continuous variables, depending on data distribution.

Вмешательства

• Препарат oral-spray 0.9% NaCl physiological saline solution
  The oral-spray 0.9% NaCl physiological saline solution is prepared by extracting 20 mL from a 500 mL polypropylene bottle of 0.9% NaCl intravenous infusion (B. Braun, Germany; product declaration No. VD-32732-19). The solution is contained in an opaque plastic spray bottle identical to that used for the administration of Smile Care.
• Комбинированный продукт LiveSpo Smile CARE
  LiveSpo Smile CARE is manufactured as a Class-A medical device (product declaration 250002196/PCBA-HN) in compliance with manufacturing standards approved by the Hanoi Department of Health, Ministry of Health. The product is formulated as a 0.9% NaCl physiological saline solution plus Bacillus subtilis ANA48 and Bacillus clausii ANA39 at total concentration of ≥ 1 billion CFU/ (20 billion CFU/20 mL suspension)

Первичные конечные точки

• Oral health indicators [Срок оценки: Days 0, 7, 14, 28 and 42]
• Periodontal parameters [Срок оценки: Days 0, 7, 14, 28 and 42]

Вторичные конечные точки (2)

• Changes in pro-inflammatory cytokine and IgA levels in gingival crevicular fluid samples at days 0, 7, 14, 28, and 42 [Срок оценки: Days 0, 7, 14, 28, and 42]
• Changes in the concentration of pathogenic bacteria around the teeth [Срок оценки: Days 0, 7, 14, 28, and 42]

Критерии участия

Критерии включения

• Patients aged 35 years and older.
• Patients diagnosed with periodontal disease based on clinical examination, including gingivitis and periodontitis.
• Patients presenting with at least 10 natural teeth in the dental arch.
• Patients with stable general health status and able to comply with study procedures.
• Patients (or their legal guardians) who provide written informed consent and voluntarily agree to participate in the study.

Критерии исключения

• Patients with unstable general health, acute systemic or oral diseases, or malignant conditions that may interfere with participation.
• Patients who are currently receiving treatment for periodontal disease at specialized dental facilities.
• Patients currently using any therapeutic or adjunctive products for the management of periodontal disease.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Вьетнам · 1 центр

• Tuyet Thai Senior Care Center — Hanoi

Публикации

• Huang Q, Dong X. Prevalence of periodontal disease in middle-aged and elderly patients and its influencing factors. Am J Transl Res. 2022 Aug 15;14(8):5677-5684. eCollection 2022. PMID 36105065
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• Dang HT, Tran DM, Phung TTB, Bui ATP, Vu YH, Luong MT, Nguyen HM, Trinh HT, Nguyen TT, Nguyen AH, Van Nguyen AT. Promising clinical and immunological efficacy of Bacillus clausii spore probiotics for supportive treatment of persistent diarrhea in children. Sci Rep. 2024 Mar 18;14(1):6422. doi: 10.1038/s41598-024-56627-9. PMID 38494525
• Aleti G, Sessitsch A, Brader G. Genome mining: Prediction of lipopeptides and polyketides from Bacillus and related Firmicutes. Comput Struct Biotechnol J. 2015 Mar 24;13:192-203. doi: 10.1016/j.csbj.2015.03.003. eCollection 2015. PMID 25893081
• Bader J, Albin A, Stahl U. Spore-forming bacteria and their utilisation as probiotics. Benef Microbes. 2012 Mar 1;3(1):67-75. doi: 10.3920/BM2011.0039. PMID 22348911
• Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol. 2008 Aug;79(8 Suppl):1585-91. doi: 10.1902/jop.2008.080183. PMID 18673014
• Fontana M, Zero DT. Assessing patients' caries risk. J Am Dent Assoc. 2006 Sep;137(9):1231-9. doi: 10.14219/jada.archive.2006.0380. PMID 16946427
• Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M, Haytac MC. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol. 2013 Nov;40(11):1025-35. doi: 10.1111/jcpe.12155. Epub 2013 Sep 15. PMID 24164569

Идентификаторы

NCT: NCT07258303 · TNLS.2025.NC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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