Periodontal DiseaseNCT07258303
Oral-Spray Bacillus Spore Probiotics for Periodontal Disease Prevention and Supprotive Treatment in the Elderly
A study testing oral-spray 0.9% NaCl physiological saline solution and LiveSpo Smile CARE in people with Periodontal Disease and Oral Deseases, run by Anabio R&D at 1 site in Vietnam.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 years and olderHealthy volunteers can take part
- Conditions the study is for
- Periodontal Disease, Oral Deseases
- What is being tested?
- oral-spray 0.9% NaCl physiological saline solution and LiveSpo Smile CARE
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteVietnam
- Study dates
- 20 Dec 2025to 1 May 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Vietnam1 site, 1 recruiting
- Recruiting
Tuyet Thai Senior Care Center
Hanoi, Hanoi, 100000
Hai H Nham, 0916985638, haildlddaitu@gmail.com
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Periodontal Disease, Oral Deseases
- Being tested
- oral-spray 0.9% NaCl physiological saline solution, LiveSpo Smile CARE
- Keywords
- Periodontal Disease, The elderly, pathogenic bacterial densities, Bacillus, Spores, oral-spray probiotics
- Medical subject headings
- Periodontal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral-spray 0.9% NaCl physiological saline solutionDrug
Also called Registration number: VD-32723-19
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.
LiveSpo Smile CARECombination product
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)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants allocated to the placebo group will receive a 0.9% NaCl physiological saline spray. The solution will be self-administered via spray, twice daily-once in the afternoon and once at night. At each administration, participants will apply two sprays to each side of the dental arch and two sprays to the incisor region, resulting in a total of six sprays per application. This regimen will be maintained consistently for a period of 4 weeks. Receives: Drug: oral-spray 0.9% NaCl physiological saline solution |
| Smile Care | Experimental | Participants assigned to the experimental group will receive LiveSpo® Smile CARE (20 mL), formulated as an oral-spray probiotics containing ≥ 1 × 10⁹ CFU/ mL of Bacillus subtilis and Bacillus clausii, of 0.9% sodium chloride solution. The suspension will be self-administered via oral spray twice daily once in the afternoon and once at night. At each administration, participants will apply two sprays to each side of the dental arch and two sprays to the incisor region, totaling six sprays per application. The intervention will be continued for a duration of 4 weeks. Receives: Combination Product: LiveSpo Smile CARE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral health indicators
Percentage of teeth classified according to a grading scale (good, moderate, and severe) for the following parameters: Simple Debris Index (DI-S), Gingival Index (GI), Bleeding on Probing (BOP), and Halitosis (score 1-4) is assessed at various time points relative to day 0.
Measured: Days 0, 7, 14, 28 and 42
Periodontal parameters
Periodontal parameters are assessed for the following: Recession of the Gingival Margin (REC, mm), Probing Depth (PD, mm), and Clinical Attachment Loss (CAL, mm). These parameters are assessed at various time points relative to day 0.
Measured: Days 0, 7, 14, 28 and 42
Secondary outcomes (2)
Changes in pro-inflammatory cytokine and IgA levels in gingival crevicular fluid samples at days 0, 7, 14, 28, and 42
Changes in pro-inflammatory cytokine levels (e.g. IL-6, IL-8, TNF-alpha...) in gingival crevicular fluid samples.
Measured: Days 0, 7, 14, 28, and 42
Changes in the concentration of pathogenic bacteria around the teeth
Changes in the levels of pathogenic bacteria (P. gingivalis, A. actinomycetemcomitans, and S. mutans) in swab samples taken around the teeth will be evaluated at various time points relative to day 0.
Measured: Days 0, 7, 14, 28, and 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start20 Dec 2025
- Primary completion30 Oct 2026 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Periodontal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Blind, randomized, and controlled clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anabio R&D
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hanoi Medical University
- Responsible party
- Sponsor
- Investigators
- Nga TT Pham, PhD. MD, Study chair, Hanoi Medical UniversityThu TH Nguyen, Assoc. Prof., Principal investigator, Hanoi Medical UniversityAnh TV Nguyen, Assoc. Prof., Principal investigator, Spobio Research Center, Anabio R&D
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07258303
- Sponsor's protocol ID
- TNLS.2025.NC
- Status last verified
- Jan 2026
- First submitted
- 18 Nov 2025
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data or samples share that will be coded, with no PHI include. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.
Publications
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.
PubMed 36105065Jindal G, Pandey RK, Agarwal J, Singh M. A comparative evaluation of probiotics on salivary mutans streptococci counts in Indian children. Eur Arch Paediatr Dent. 2011 Aug;12(4):211-5. doi: 10.1007/BF03262809.
PubMed 21806906Dang 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.
PubMed 38494525Aleti 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.
PubMed 25893081Bader 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.
PubMed 22348911Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol. 2008 Aug;79(8 Suppl):1585-91. doi: 10.1902/jop.2008.080183.
PubMed 18673014Fontana M, Zero DT. Assessing patients' caries risk. J Am Dent Assoc. 2006 Sep;137(9):1231-9. doi: 10.14219/jada.archive.2006.0380.
PubMed 16946427Teughels 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.
PubMed 24164569Amaliya A, Laine ML, Delanghe JR, Loos BG, Van Wijk AJ, Van der Velden U. Java project on periodontal diseases: periodontal bone loss in relation to environmental and systemic conditions. J Clin Periodontol. 2015 Apr;42(4):325-32. doi: 10.1111/jcpe.12381. Epub 2015 Mar 24.
PubMed 25683157Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol. 2012 Dec;27(6):409-19. doi: 10.1111/j.2041-1014.2012.00663.x. Epub 2012 Sep 3.
PubMed 23134607Perez-Chaparro PJ, Duarte PM, Shibli JA, Montenegro S, Lacerda Heluy S, Figueiredo LC, Faveri M, Feres M. The Current Weight of Evidence of the Microbiologic Profile Associated With Peri-Implantitis: A Systematic Review. J Periodontol. 2016 Nov;87(11):1295-1304. doi: 10.1902/jop.2016.160184. Epub 2016 Jul 15.
PubMed 27420109Perez-Chaparro PJ, Goncalves C, Figueiredo LC, Faveri M, Lobao E, Tamashiro N, Duarte P, Feres M. Newly identified pathogens associated with periodontitis: a systematic review. J Dent Res. 2014 Sep;93(9):846-58. doi: 10.1177/0022034514542468. Epub 2014 Jul 29.
PubMed 25074492