Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Healozone Study to Evaluate the Safety and Efficacy of the Use of Ozone for Management of Dental Caries

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00495495
Recruitment Status : Completed
First Posted : July 3, 2007
Results First Posted : December 23, 2010
Last Update Posted : February 20, 2015
Sponsor:
Collaborators:
Tufts University School of Dental Medicine
State University of New York at Buffalo
Information provided by (Responsible Party):
Indiana University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Prevention
Condition Dental Caries
Interventions Device: Ozone treatment
Device: Placebo treatment
Enrollment 394
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ozone Treatment and Placebo Treatment
Hide Arm/Group Description 60-second Ozone device treatment compared to 60-second Placebo device treatment. Study utilized split-mouth design. The paired treatment assignment for the two teeth within each subject was performed according to a randomization table provided by the Biometrician. Randomization of teeth to Ozone treatment or Placebo treatment was stratifed according to tooth similarity.
Period Title: Overall Study
Started 394
Completed 295
Not Completed 99
Reason Not Completed
Protocol Violation             99
Arm/Group Title Ozone Treatment/Placebo Treatment
Hide Arm/Group Description Study utilized split-mouth design. Each participant had two teeth selected at the start of the study. Each participant was then randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds and Placebo treatment on a randomly selected study tooth for 60 seconds.
Overall Number of Baseline Participants 394
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 394 participants
<=18 years
102
  25.9%
Between 18 and 65 years
292
  74.1%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 394 participants
22.9  (7.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 394 participants
Female
202
  51.3%
Male
192
  48.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 394 participants
394
1.Primary Outcome
Title ICDAS Severity Value
Hide Description

Clinically significant changes indicating caries progression are defined as changes in ICDAS severity values from 1 or 2 to a 3 or higher, or from a 3 or 4 to a 5 or higher. The severity criteria 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.
Time Frame Baseline and One Year
Hide Outcome Measure Data
Hide Analysis Population Description
The study utilized a split-mouth design. The results posted are for the Per Protocol dataset. Subjects who completed all four treatment/examination visits as well as final examination visit without major protocol violations were included in this dataset.
Arm/Group Title Ozone Treatment Placebo Treatment
Hide Arm/Group Description:
As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.
As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Overall Number of Participants Analyzed 295 295
Overall Number of Units Analyzed
Type of Units Analyzed: Teeth
295 295
Measure Type: Number
Unit of Measure: teeth
Number of Teeth with Caries Progression 17 22
Number of Teeth with No Caries Progression 278 273
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ozone Treatment
Comments

Null hypothesis: there is no difference between the HealOzone and Placebo devices in the proportion of teeth with lesion progression after 1 year.

Power calculation: the study was sized to have 90% power to detect a 15% difference between treatments in the percentage of teeth with lesion progression at one year (i.e., assuming 45% for the lesions treated with the Placebo device and 30% for the lesions treated with the HealOzone device) with a sample size of 258 subjects completing the study.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1126
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value .02
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Caries Lesion Activity
Hide Description

Change in caries lesion activity at One Year. All teeth were considered Active at Baseline

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.
Time Frame Baseline and one year
Hide Outcome Measure Data
Hide Analysis Population Description

Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations.

Clinically significant changes for Activity Scores were indicated by a change in caries activity status from active to inactive. It should be noted that all teeth were considered active at baseline.

Arm/Group Title Ozone Treatment Placebo Treatment
Hide Arm/Group Description:
As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.
As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Overall Number of Participants Analyzed 295 295
Overall Number of Units Analyzed
Type of Units Analyzed: Teeth
295 295
Measure Type: Number
Unit of Measure: teeth
Number of Active Caries lesions 189 164
Number of Non- Active Caries Lesions 106 131
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ozone Treatment, Placebo Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .9777
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value .08
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Progression of Radiographic Scores at 12 Months
Hide Description

Clinically significant changes for Bitewing x-rays indicating caries progression would be changes in x-ray criterion for lesion presence from “no” to “yes” or for lesion depth to a D1 or higher. 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

Time Frame one year
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations (subjects who completed all four treatment/examination visit at Baseline, 3-, 6-, 9-month as well as Final examination at 12-month.
Arm/Group Title Ozone Treatment Placebo Treatment
Hide Arm/Group Description:
As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.
As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Overall Number of Participants Analyzed 295 295
Overall Number of Units Analyzed
Type of Units Analyzed: Teeth
295 295
Measure Type: Number
Unit of Measure: teeth
Number of Teeth with Progression 6 12
Number of Teeth with No Progression 220 214
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ozone Treatment, Placebo Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0416
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
4.Secondary Outcome
Title Laser Fluorescence Progression-12 Month (Increase From <=20 to >=30)
Hide Description The change in DIAGNOdent measurements between baseline and twelve-month visits was used as an additional secondary endpoint. Clinically significant changes for DIAGNOdent indicating caries progression would be an increase in DIAGNOdent reading of 10 or more units or an increase in DIAGNOdent reading from below 20 to above 30 units. DIAGNOdent reading using a scale from 00 to 99, with 00 indicating no caries activity and 99 indicating a high level of activity.
Time Frame one year
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations (subjects who completed all four treatment/examination visit at Baseline, 3-, 6-, 9-month as well as Final examination at 12-month.
Arm/Group Title Ozone Treatment Placebo Treatment
Hide Arm/Group Description:
As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.
As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Overall Number of Participants Analyzed 293 293
Overall Number of Units Analyzed
Type of Units Analyzed: Teeth
293 293
Measure Type: Number
Unit of Measure: teeth
Number of Teeth with Progression 16 14
Number of Teeth with No Progression 277 279
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ozone Treatment, Placebo Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6585
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value .01
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Laser Fluorescence Progression-12 Month (Increase at Least 10)
Hide Description The change in DIAGNOdent measurements between baseline and twelve-month visits was used as an additional secondary endpoint. Clinically significant changes for DIAGNOdent indicating caries progression would be an increase in DIAGNOdent reading of 10 or more units. DIAGNOdent reading using a scale from 00 to 99, with 00 indicating no caries activity and 99 indicating a high level of activity.
Time Frame one year
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations.
Arm/Group Title Ozone Treatment Placebo Treatment
Hide Arm/Group Description:
As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.
As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Overall Number of Participants Analyzed 293 293
Overall Number of Units Analyzed
Type of Units Analyzed: Teeth
293 293
Measure Type: Number
Unit of Measure: teeth
Number of Teeth with Progression 58 52
Number of Teeth with No Progression 235 241
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ozone Treatment, Placebo Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .7666
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value .02
Estimation Comments [Not Specified]
Time Frame The adverse events were collected during the one-year period of the trial.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ozone Treatment and Placebo Treatment
Hide Arm/Group Description Study utilized split-mouth design. Each participant had two teeth selected at the start of the study. Each participant was then randominzed to receive Ozone treatment on a randomly selected study tooth for 60 seconds and Placebo treatment on a randomly selected study tooth for 60 seconds.
All-Cause Mortality
Ozone Treatment and Placebo Treatment
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ozone Treatment and Placebo Treatment
Affected / at Risk (%) # Events
Total   5/394 (1.27%)    
General disorders   
Appendicitis  [1]  1/394 (0.25%)  1
Musculoskeletal and connective tissue disorders   
Broken left leg  [1]  1/394 (0.25%)  1
Broken left knee  [1]  1/394 (0.25%)  1
Reproductive system and breast disorders   
Surgery ovarian cyst removal * [1]  1/394 (0.25%)  1
surgery breast reduction  [1]  1/394 (0.25%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
Not related to ozone device
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ozone Treatment and Placebo Treatment
Affected / at Risk (%) # Events
Total   0/394 (0.00%)    
Study length may have been too brief to permit progression of early stage caries; Low caries increment in study population; Difficult to establish that lesions were truly active at baseline.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Domenick T. Zero, DDS MS Principal Investigator
Organization: Indiana University School of Dentistry
Phone: 317-274-8822
EMail: dzero@iupui.edu
Layout table for additonal information
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00495495     History of Changes
Other Study ID Numbers: 07-D-187
IDE G50008
Clinical Trials. gov ( Registry Identifier: ClinicalTrials.gov protocol registration system )
First Submitted: July 1, 2007
First Posted: July 3, 2007
Results First Submitted: October 12, 2010
Results First Posted: December 23, 2010
Last Update Posted: February 20, 2015