Healozone Study to Evaluate the Safety and Efficacy of the Use of Ozone for Management of Dental Caries
Condition: Dental Caries
MeSH terms: Dental Caries
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Caries means demineralization with the formation of cavities and pulp symptoms and necrosis
      as an end result. The acids in the mouth are mainly produced by oral bacteria like
      Streptococcus mutans from bacterial biofilms adhering to the tooth. Ozone has been shown to
      have a very strong bactericidal effect on bacteria causing dental caries. Baysan et al
      reported that there was a statistically significant reduction of streptococci in root caries
      lesions and saliva samples after ozone application. The positive clinical effect of ozone
      with respect to arresting caries progression and the remineralization of caries has been
      shown in vitro and in vivo. In an in vivo study, Baysan and Lynch found that the application
      of ozone resulted in a significant reduction of bacterial contamination as well as a
      reduction in size and severity of root caries lesions. In a subsequent study, Baysan and
      Lynch reported that the severity of root caries lesions was significantly reduced after ozone
      application as measured by electrical conductance and laser fluorescence. In several studies,
      the caries reducing effect of ozone was measured with biochemical methods in root surface
      caries lesions, the biofilm and saliva after ozone application. See Citation section for
      references.

      The objectives of this multi-center clinical study were to determine: (1) the effectiveness
      of the HealOzone in stopping the progression of fissure caries; and (2) the oral soft tissue
      safety of the ozone system.
    

Detailed description: 
      The proposed study was designed as a twelve-month, multi-center, double-blind, randomized
      controlled clinical study involving 394 subjects with 788 lesions. There were three sites
      participating in this trial: Indiana University School of Dentistry (lead site), Tufts
      University School of Dental Medicine, and SUNY School of Dental Medicine. Each site submitted
      a version of the protocol to their respective Institutional Review Board ("IRB") that
      incorporated the specific institutional and state guidelines and regulations applicable to
      that site.

      The two treatment regimens were: (a) placebo treatment and (b) experimental ozone treatment.
      Selected subjects had to have at least two teeth with similar stages of early active fissure
      caries. The selection of the study teeth was determined by a review of the visual
      examination, including the ICDAS severity score and the caries lesion activity score,
      conducted at the screening visit, in conjunction with the bitewing radiographs. The decision
      whether a tooth was to be treated with ozone or receive placebo treatment was made randomly.

      All clinical personnel involved in the clinical examinations and treatment application were
      trained at the primary site prior to the initiation of the trial both in the use of the
      device, and in how to identify the signs and symptoms of ozone toxicity and in how to provide
      the appropriate medical response should any of these signs or symptoms be observed.

      All qualified subjects received the following:

        1. Professional dental cleaning and scaling at the Screening Visit (or separate visit prior
           to baseline visit and after completing the study at 12 months.

        2. Diagnostic procedures:

             1. Clinical visual examination (utilizing the International Caries Detection and
                Assessment System [ICDAS] severity scoring)

             2. Clinical visual/tactile assessment of caries lesion activity

             3. Bitewing x-rays

             4. Laser fluorescence measurement (utilizing the DIAGNOdent, KaVo)

        3. Treatment Regimen:

      Using a split-mouth design, the assigned investigational treatment regimen was administered
      on the two selected study teeth at the baseline, and at the three-, six- and nine-month
      appointments.

      After three, six, nine and twelve months, the diagnostic procedures were repeated with the
      exception of bitewing x-rays, which were only repeated at the twelve-month exam (unless the
      examining dentist determined that x-rays also were needed at the six- or nine-month visit to
      confirm whether dentinal caries were present). In addition, optional digital photographs were
      taken at the Boston site of selected study teeth to document clinical changes over the study
      period.

      If a selected study tooth progressed from an initial caries lesion to a more advanced lesion,
      which in the judgment of the examining dentist required restorative intervention, the tooth
      was restored at no cost to the subject and the lesion was recorded as 'progression from
      baseline' at any remaining examinations. The subject was eligible to remain in the study.

      Subjects received a thorough dental cleaning and scaling and topical fluoride treatment at
      the conclusion of the twelve-month examination.

      The primary efficacy parameter will be the ICDAS severity value. The severity criteria used
      in the ICDAS diagnostic system are as follows:

      0 = Sound tooth surface.

        1. = First visual change in enamel.

        2. = Distinct visual change in enamel.

        3. = Localized enamel breakdown due to caries with no visible dentin.

        4. = Underlying dark shadow from dentin, with or without localized enamel breakdown.

        5. = Distinct cavity with visible dentin.

        6. = Extensive distinct cavity with visible dentin.

      The secondary efficacy parameters will be measured by:

      Caries Lesion Activity score:

        1. = Inactive - surface of enamel appears whitish, brownish or black. Enamel may be shiny
           and feels hard and smooth when the tip of the probe is moved gently across the surface.

        2. = Active lesion - surface of enamel appears whitish/yellowish opaque with loss of
           luster. The surface feels rough when the tip of the probe is moved gently across the
           surface.

      Radiographic Changes:

      The occlusal surface of study teeth will be evaluated using the following scale:

      Lesion presence: yes /no

      Lesion depth:

      E1 = outer half of enamel E2 = inner half of enamel D1 = outer third of dentin D2 = middle
      third of dentin D3 = inner third of dentin or greater/pulpal exposure

      Laser fluorescence measurement:

      DIAGNOdent reading using a scale from 00 to 99, with 00 indicating no caries activity and 99
      indicating a high level of activity.
    

Intervention name(s): Ozone treatment; Placebo treatment
Intervention type(s): Device; Device
Intervention description(s): Ozone treatment applied to randomly selected tooth for a period of 60 seconds at Baseline, Three, Six and Nine-Month visits.; Placebo treatment applied to randomly selected tooth for a period of 60 seconds at Baseline, Three-, Six- and Nine-Month visits.
Other intervention name(s): HealOzone unit
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention