Study to Evaluate the Clinical Efficacy of Streptococcus Dentisani CECT 7746 in Caries Risk Reduction
Condition: Caries
Study type: Interventional
Phase: Phase 1

Summary: 
      Exploratory, phase I study to evaluate the clinical efficacy of Streptococcus dentisani CECT
      7746 in the risk reduction of caries. Patients who meet the inclusion and exclusion criteria
      will be randomized and receive the corresponding treatment. The study will follow a
      randomized design, with two groups in parallel (placebo group and probiotic group) of
      prospective, double-blind follow-up, for a period of 45 days. The present study will be
      conducted in a single center and will include a total of 70 patients. The present study has a
      double main objective:

        -  Evaluate whether the administration of the probiotic S. dentisani CECT 7746 alkalizes
           the basal pH of saliva.

        -  Test the safety and tolerability of the probiotic

      Secondary

        -  Evaluate other microbiological parameters associated with caries risk such as the
           presence of microorganisms such as S. mutans.

        -  Evaluate the presence in the mouth and colonization capacity of S. dentisani.

        -  Evaluate the lactic acid and the pH of the ex vivo plate before and after the
           administration of a sugar solution

        -  Evaluate the salivary pH before and after the administration of a sugar solution

        -  Evaluate the salivary pH before brushing with water.

        -  Evaluate the buffer capacity of saliva
    

Detailed description: 
      The probiotic Streptococcus dentisani is a bacterial species present in the human oral
      microbial flora. It was isolated initially, as result of observation and hypothesis, of
      volunteers who had never developed caries. These strains have demonstrated, through in vitro
      studies, an enormous potential of inhibition against S. mutans, besides inhibiting the growth
      of other pathogens commonly present in common oral pathologies (gingivitis, periodontitis or
      halitosis). The probiotic product has been shown to be effective in in vitro experiments,
      artificial mouth models and epidemiological data, statistically significant. However, it is
      necessary to document the efficacy of Streptococcus dentisani in an oral application study.

      Recruitment visit:

      In a first visit, it will be assessed if the candidates meet all the inclusion criteria and
      none of the exclusion criteria. For this, a dental revision will be carried out to assess the
      different parameters (plaque index, gingival index and salivary flow among others), and a
      saliva sample will be taken after brushing with water to determine its basal pH.

      Those participants who meet the criteria and provide written informed consent will be
      assigned to one of the two treatment groups (probiotic or placebo). The assignment will be
      done randomly using a computer generated list.

      In this first visit, an impression of the jaw will also be made of those volunteers who meet
      the criteria and have been randomized. This impression will be used to manufacture custom
      splints that allow a more comfortable application of the treatment during the study by the
      participants.

      A detailed list of probiotic products present in the market for oral use will be provided.

      Basal visit (Day 0):

      After 1-2 weeks of the recruitment visit, participants will return to the center for the
      baseline visit. During this visit, samples of saliva (2 ml) and plaque (from quadrants 1 and
      3 on the vestibular and lingual surfaces) will be taken for the quantification and detection
      of S. mutans and Streptococcus dentisani, and plaque samples of quadrants 2 and 4 by the
      vestibular and lingual surfaces to quantify the lactic acid produced by the ex vivo plaque,
      and its pH. The pH of the saliva will also be evaluated before and after brushing with only
      water and then measured before and after a rinse with active movements with 10 ml of a 10%
      sugar solution for 1 minute. Finally, the buffering capacity of the saliva, measured by the
      amount of acid that the saliva is capable of buffering using reactive strips, will be
      evaluated.

      The participants will be treated with probiotic or placebo, depending on the group to which
      they have been assigned, without the participant or the researcher knowing the assigned
      treatment. For this the two products will present the same appearance. The randomization will
      remain blind until the end of the study.

      The treatment will consist of the application of the product in the form of gel by all the
      free surfaces of the teeth by means of a splint. The production of the splints will be done
      by the same recruiting center. These are washable and reusable splints during the entire
      study treatment.

      The first treatment will be carried out during the baseline visit and will be applied by the
      clinic professional, who will explain to the participant how to perform successive
      applications at home every 48 hours.

      Participants will receive the splint and the exact number of doses of probiotic or placebo
      needed for the next visit, which they should return in a bag to verify that the treatment has
      been followed correctly. Likewise, volunteers will receive a fluoride toothpaste (1000 ppm),
      a toothbrush and instructions on how to maintain healthy hygiene habits to standardize study
      conditions. The use of mouthwashes and oral probiotic consumption will be expressly
      prohibited during the study, all participants will receive a copy of Annexes I and II with
      the list of mouthwash and probiotic products not admitted.

      Visit 1 (Day 15 ± 2 days, follow-up visit):

      In this visit participants will be asked to deliver the unused material and they will be
      provided with the treatments in the exact dosage number until the next visit, as well as the
      elements for oral hygiene. The appearance of any adverse effect during the consumption of the
      product will be reviewed with the patient, for it a dental revision will be carried out to
      evaluate different parameters (plaque index, gingival index and salivary flow among others).
      During this visit, samples of saliva (2 ml) and plaque (from quadrants 1 and 3 on the
      vestibular and lingual surfaces) will be taken for the quantification and detection of S.
      mutans and Streptococcus dentisani, and plaque samples of quadrants 2 and 4 by the vestibular
      and lingual surfaces to quantify the lactic acid produced by the ex vivo plaque, and its pH.
      The pH of the saliva will also be evaluated before and after brushing with only water and
      then measured before and after a rinse with active movements with 10 ml of a 10% sugar
      solution for 1 minute. Finally, the buffer capacity of saliva will be evaluated.

      During this visit, the clinic professional will once again apply the product to all
      participants and remind them how successive applications should be made at their home every
      48 hours.

      Visit 2 (Day 30 ± 2 days, end of treatment):

      The same procedure will be followed as in visit 1 (day 15), but new single doses will not be
      provided.

      Visit 3 (Day 45 ± 2 days, final visit):

      During this visit, samples of saliva (2 ml) and plaque (from quadrants 1 and 3 on the
      vestibular and lingual surfaces) will be taken for the quantification and detection of S.
      mutans and Streptococcus dentisani, and plaque samples of quadrants 2 and 4 by the vestibular
      and lingual surfaces to quantify the lactic acid produced by the ex vivo plaque, and its pH.
      The pH of the saliva will also be evaluated before and after brushing with only water and
      then measured before and after a rinse with active movements with 10 ml of a 10% sugar
      solution for 1 minute. Finally, the buffer capacity of saliva will be evaluated.
    

Intervention name(s): Probiotic; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): Already described; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study will follow a randomized, double-blind, placebo-controlled design with 2 parallel prospective follow-up groups.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Streptococcus dentisani; caries; salivary pH; S. mutans