SmartMouth Advanced Clinical Formula Clinical Research Design Protocol

Study Overview
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Brief Summary
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The aim of this study is to provide evidence on the clinical efficacy of SmartMouth Advanced Clinical Formula mouthrinse in comparison to the efficacy of 0.12% chlorhexidine mouthrinse and a placebo mouthrinse. The placebo will be provided by the sponsor and will be identical to SmartMouth ACF (Advanced Clinical Formula), except it will not contain cetylpyridinium chloride, zinc chloride and sodium chlorite. The primary outcomes include measures of plaque and gingivitis. Secondary outcomes include evaluation of tooth discoloration, taste perception, malodor and calculus.

Detailed Description
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Study Population A 10 week double-blinded, randomized clinical study will be conducted on 80 subjects diagnosed with plaque induced gingivitis and/or chronic periodontitis. The study will take place at Saint Louis University Center for Advanced Dental Education and Southern Illinois University School of Dental Medicine. Research Design and Methods Visit 1 Subjects who sign the informed consent and medical history forms and meet the preliminary entrance criteria will be examined at baseline. All participants will be informed of the nature of the study, its purpose, and any possible risks. Subjects will also be informed as to the length of the study and the specific procedures that will be carried out. Subjects will be informed that this is a voluntary study and that they are free to withdraw from the study at any time. Clinical measurements of plaque and gingival indices will be taken. A gingival bleeding score will be determined. Examiners will be standardized for scoring. Gingival index (GI) will be measured using the Loe and Silness method (Loe and Silness 1963). The gingiva will be scored at six sites of each tooth (distobuccal, buccal, mesiobuccal, distolingual, lingual, mesiolingual) and given a score from 0 - 3. By adding the scores and dividing by the total number of sites, the GI for the patient will be obtained. The following criteria will be used for scoring: 0 - Absence of inflammation - Mild inflammation: slight change in color, slight edema; no bleeding upon probing - Moderate inflammation: Redness, edema, and glazing; bleeding upon probing - Severe inflammation: Marked redness and edema; ulceration; tendency to spontaneous bleeding Sites with GI scores of 2 or 3 will be counted as bleeding. A whole mouth total gingival bleeding score will be calculated by summing the number of bleeding sites and dividing by the number of teeth. Plaque will be scored based on the Turesky modification of the Quigley-Hein Plaque Index (PI) (Turesky 1970). A score of 0 - 5 will be assigned to six sites of each tooth (distobuccal, buccal, mesiobuccal, distolingual, lingual, mesiolingual) following the use of a disclosing solution. The following criteria will be used: 0 - No plaque - Isolated areas of plaque at gingival margin - Thin continuous band of plaque at gingival margin (up to 1 mm) - Band of plaque ˃ 1 mm and ˂ 1/3 of the tooth surface - Plaque covering 1/3 to ˂ 2/3 of tooth surface - Plaque covering ≥ 2/3 of tooth surface The Plaque Index for the entire mouth will be determined by dividing the total score by the number of surfaces examined. The Gingival Index will be measured prior to the Plaque Index. Teeth with gross caries and third molars will not be scored with either index. Extrinsic tooth stain will be scored on the facial surfaces of the 8 incisor teeth using a modification of the Lobene tooth stain index (SI) (Lobene 1968). Each incisor will be scored for stain area on a scale of 0-3. The sum of the stain scores for the subject will be used as that subject's stain score. Scores will be recorded from 0 to 3 as follows: 0: no stain detected, only tooth color stain over 1/3 of the surface stain over 2/3 of the surface stain over more than 2/3 of the surface Supragingival calculus on the lingual surfaces of the six mandibular anterior teeth will be scored using the Volpe-Manhold calculus index (CI) (Volpe et al. 1965). The supragingival calculus in three defined planes on the lingual surface of each tooth will be measured using a periodontal probe. The measurements will be added and a mean subject score will be calculated. A complete periodontal examination will be performed for all subjects that meet the inclusion criteria. A panoramic radiograph will be taken for all subjects that do not have full mouth radiographs within the last year. Safety assessments will be made at each measurement visit. Assessment of the oral soft tissues will be conducted at each visit by visual examination of the oral cavity. All areas will be assessed and reported as normal or abnormal. Subject compensation: all subjects entered into the study will be given a gift card at the end of visit 2, visit 3 and visit 4. Visit 2 Visit 2 will occur within 4 weeks of Visit 1. Subjects entered into the study will be randomly assigned to three groups: Group 1 (Smart Mouth ACF), Group 2 (0.12% chlorhexidine) or Group 3 (placebo). All subjects will be given a complete dental prophylaxis to remove plaque, calculus, and stain. Written and verbal oral hygiene instructions will be given that include a regular regimen of brushing twice daily and flossing daily. All subjects will be assigned a commercially available ADA accepted toothbrush and dental floss. They will be given a 3 week supply of the assigned mouthrinse with written and verbal instructions for use. Subjects will be instructed not to have their teeth professionally cleaned prior to study completion. All mouthrinses will be in a plain package and dispensed by the faculty investigators. The package will be labeled with a code to indicate the product. Only the faculty investigators will have access to the code information. Directions for use will be contained in the package. The examiners will not see the product. The examiners will give instructions for mouthrinse use, but they will not be aware which rinse the subjects are using. Each product will contain two solutions which are mixed prior to use. Visit 3 Subjects will be examined 3 weeks after visit 2. All clinical measurements will be repeated. Each subject will return with any unused rinse or two empty bottles of rinse. Compliance will be determined by regulating the amount of rinse dispensed on a 3 week basis and by the measurement of any unused rinse at the end of two 3 week periods. Additional rinse will be given to each subject after visit 3 for use until the final visit. Visit 4 Subjects will be examined 3 weeks after visit 3 (6 weeks from visit 2). Clinical measurements will be repeated. Each subject will return with any unused rinse or two empty bottles of rinse. Compliance will be determined by the measurement of any unused rinse at the end of the study. Subjects will be given a survey to answer questions about their experience with the mouthrinse. Prophylaxis may be performed at this visit. Following the study, the subjects will be treated by their provider's discretion.

Official Title
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SmartMouth Advanced Clinical Formula Clinical Research Design Protocol

Conditions
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Gingivitis, Periodontitis

Intervention / Treatment
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* Drug: SmartMouth Clinical DDS mouthrinse
* Drug: 0.12% chlorhexidine rinse
* Drug: Placebo rinse


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between the ages of 18 to 80 Subjects with a diagnosis of gingivitis or chronic periodontitis Entry levels of gingival inflammation and plaque accumulation will be present (mean Gingival Index ≥ 0.4 and Plaque Index ≥ 1.0) Subjects that are in good medical health at time of the study At least 20 permanent natural teeth Exclusion Criteria: Use of local or systemic antibiotics during the course of the study Subjects that are pregnant or nursing mothers Subjects undergoing orthodontic therapy Subjects wearing removable prostheses Subjects taking medication which is altering the gingiva or causing inflammation Gingival overgrowth History of sensitivity or suspected allergies following the use of oral hygiene products Subjects taking anti-inflammatory or anticoagulant medications that would alter the gingiva and promote bleeding Subjects that require antibiotic prophylaxis prior to dental treatment Subjects that have acute dental problems requiring immediate treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 SmartMouth<br>24 subjects with plaque and gingival inflammation | Drug: SmartMouth Clinical DDS mouthrinse<br>* Subjects use SmartMouth Clinical DDS mouth rinse for six weeks.<br>|
| Experimental: Group 2 Chlorhexidine<br>28 subjects with plaque and gingival inflammation | Drug: 0.12% chlorhexidine rinse<br>* Subjects use chlorhexidine mouth rinse for six weeks.<br>|
| Placebo Comparator: Group 3 Placebo<br>28 subjects with plaque and gingival inflammation | Drug: Placebo rinse<br>* Subjects use placebo mouth rinse for six weeks. The placebo rinse is the same as SmartMouth Clinical DDS, but without the active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gingival Index | Gingival Index scores gingival inflammation from 0 (healthy) to 3 (severe inflammation). The higher the score, the greater the gingival inflammation (worse outcome). Differences were assessed between treatment groups for changes in values from baseline to 6 weeks. If data were normally distributed, the paired t test was used to assess changes; otherwise the Wilcoxon signed rank test was used. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculus Index | Calculus Index scores the amount of calculus accumulation by adding surfaces from the lingual of the mandibular anterior teeth. The higher the score, the worse the calculus accumulation. Differences were assessed between treatment groups for changes in values from baseline to 6 weeks. If data were normally distributed, the paired t test was used to assess changes; otherwise the Wilcoxon signed rank test was used. | 6 weeks | 
| Tooth Stain Index | Tooth Stain Index scores the amount of tooth stain from 0 (no stain) to 3 (greater than 2/3 of surface). The higher the score, the worse the staining. Differences were assessed between treatment groups for changes in values from baseline to 6 weeks. If data were normally distributed, the paired t test was used to assess changes; otherwise the Wilcoxon signed rank test was used. The score (0-3) for each tooth are summed for the total score. The 8 incisor teeth are scored. The minimum score for a subject is 0 and the maximum score for a subject is 24 (worse outcome). | 6 weeks | 
| Plaque Index | Plaque Index scores plaque accumulation from 0 (no plaque) to 5 (plaque covering 2/3 of surface or more). The higher the score, the more plaque accumulation (worse outcome). Differences were assessed between treatment groups for changes in values from baseline to 6 weeks. If data were normally distributed, the paired t test was used to assess changes; otherwise the Wilcoxon signed rank test was used. | 6 weeks | 
| Bleeding Score | Bleeding Score is determined by adding the number of bleeding sites and dividing by the number of teeth to assess gingival inflammation. The higher the score, the worse the inflammation. Differences were assessed between treatment groups for changes in values from baseline to 6 weeks. If data were normally distributed, the paired t test was used to assess changes; otherwise the Wilcoxon signed rank test was used. | 6 weeks |