To Evaluate Efficacy and Tolerability of Sodium Bicarbonate Toothpaste and Its Effect on Opportunistic or Resistant Organisms

Study Overview
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Brief Summary
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This study will compare the Gingival Bleeding and Gingival Inflammation following twice daily use of a sodium bicarbonate experimental dentifrice compared to a 0% sodium bicarbonate toothpaste after 24 weeks of use. The study will be conducted at Salus Research, Inc. Participants will be recruited from their database and by use of an external recruitment agency

Detailed Description
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This study will be a single-centre, examiner blind, two treatment, parallel group, stratified (by baseline number of bleeding sites smoking status and bacterial sampling) randomized clinical study. At the screening visit, following provision of written informed consent, eligible participants will be provided with a standard toothpaste and toothbrush for brushing once in at the clinic and for approximately one week use at home until the baseline visit. Participants will be asked to abstain from brushing over a 12 hour period prior to the Baseline visit. At the baseline visit an oral soft tissue (OST) assessment, Modified Gingival Index (MGI) and Bleeding Index (BI), and then dental plaque assessment will be performed. Participants will be stratified according to their baseline number of bleeding sites, smoking status and whether selected for bacterial sampling. Participants will be then randomized into one of two treatment groups. After using, their assigned treatment twice daily at home for 6 weeks (visit 3), 12 weeks (visit 4) and 24 weeks (visit 5), participants will return to the site with overnight plaque at approximately the same time of day as the Baseline visit if possible. Participants will undergo a full OST examination and the recording of any Adverse Events (AEs). Participants will then undergo MGI, BI followed by dental plaque assessment. Microbiological samples will be collected on a subset of 50 participants (Determined by first 50 participants randomized).

Official Title
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A Six Month Clinical Study Based in the US to Evaluate the Efficacy and Tolerability of Sodium Bicarbonate Toothpaste and Its Effect on Opportunistic or Resistant Organisms

Conditions
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Oral Hygiene

Intervention / Treatment
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* Drug: Sodium bicarbonate and sodium fluoride
* Drug: Sodium fluoride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or oral/dental examination. A minimum of 20 permanent gradable teeth Moderate gingivitis present at the screening visit in the opinion of the investigator A total of 20 bleeding sites or greater at baseline visit Positive response to bleeding on brushing present at the screening visit Exclusion Criteria: Pregnant or breast feeding women Tobacco chewers Current or relevant history of any serious, severe or unstable physical or psychiatric illness or any other medical condition (e.g. Diabetes Mellitus) that would make the participant unlikely to fully complete the study or any that increases the risk to the participant or undermines the data validity. Recent history (within the last year) of alcohol or other substance abuse Participants requiring prophylactic antibiotic treatment prior to dental therapy Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients Have current active caries or any medical conditions which may directly influence gingival bleeding Use of concomitant or any systemic medication that, in the opinion of the investigator, might interfere with the outcome of the study or have an effect on gingival conditions within 14 days of gingival examinations Excessive calculus present that interferes with the probing examination for Gingival Bleeding Index Participation in another clinical study or receipt of an investigational drug or oral care product within 30 days of the screening visit An employee of the sponsor or the study site or members or their immediate family.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Dentifrice<br>Participants were advised to brush their teeth with experimental dentifrice containing sodium bicarbonate plus 1150 parts per million (ppm) fluoride as sodium fluoride | Drug: Sodium bicarbonate and sodium fluoride<br>* Experimental toothpaste containing sodium bicarbonate experimental dentifrice plus 1150 parts per million (ppm) fluoride as sodium fluoride<br>|
| Active Comparator: Reference Dentifrice<br>Participants were advised to brush their teeth with reference dentifrice containing 1100ppm fluoride as sodium fluoride | Drug: Sodium fluoride<br>* Comparator toothpaste containing 1100 ppm fluoride as sodium fluoride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Gingival Bleeding Sites at 24 Weeks | The Bleeding Index was performed by a single examiner using a color coded periodontal probe. The probe was engaged approximately 1 millimetre (mm) into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI scoring system used is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed | 24 weeks | 
| Modified Gingival Index (MGI) at 24 Weeks | MGI was assessed on facial and lingual surfaces at two sites on each tooth (papillae and margin). The scoring of the MGI was performed under dental office conditions using a standard dental light for illuminating the oral cavity. Compressed air, water and mouth mirrors were available to each examiner. This procedure was performed by a single examiner. The MGI scoring system is as follows: 0 = absence of inflammation; 1 = mild inflammation; slight change in color, little change in color; little change in texture of any portion of the marginal or papillary gingival unit; 2 = mild inflammation; criteria as above but involving the entire marginal or papillar gingival units; 3= moderate inflammation; glazing, redness, edema, and/ or hypertrophy of the marginal or papillary gingival unit; 4 = severe inflammation; marked redness, edema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Gingival Bleeding Sites at 6 and 12 Weeks | BI was performed by a single examiner using a color coded periodontal probe. The probe was engaged approximately 1mm into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI scoring system used is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed | Baseline, 6 and 12 weeks | 
| Modified Gingival Index (MGI)) at 6 and 12 Weeks. | MGI was assessed on facial and lingual surfaces at two sites on each tooth (papillae and margin). The scoring of the MGI was performed under dental office conditions using a standard dental light for illuminating the oral cavity. Compressed air, water and mouth mirrors were available to each examiner. This procedure was performed by a single examiner. The MGI scoring system is as follows: 0 = absence of inflammation; 1 = mild inflammation; slight change in color, little change in color; little change in texture of any portion of the marginal or papillary gingival unit; 2 = mild inflammation; criteria as above but involving the entire marginal or papillar gingival units; 3= moderate inflammation; glazing, redness, edema, and/ or hypertrophy of the marginal or papillary gingival unit; 4 = severe inflammation; marked redness, edema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration | 6 and 12 weeks | 
| Bleeding Index (BI) at 6, 12 and 24 Weeks | BI was performed by a single examiner using a color coded periodontal probe. The probe was engaged approximately 1mm into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI scoring system used is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed | 6, 12 and 24 weeks | 
| Plaque Control (Overall and Interproximal Dental Plaque Scores) at 6, 12 and 24 Weeks. | The dental examiner had used the Turesky Modification of the Quigley Hein Index to assess plaque on all gradable teeth. Interproximal Dental Plaque Scores were analyzed in the same way as for Overall scores but just based on mesiofacial, facial, distofacial, mesiolingual, lingual and distolingual surfaces. Dental Plaque (Quigley-Hein, Turesky Modification Index) Units on a scale 0 to 5: 0= No plaque; 1= Slight flecks of plaque at the cervical margin of the tooth; 2= A thin continuous band of plaque (1 mm or smaller) at the cervical margin of the tooth; 3= A band of plaque wider than 1 mm but covering less than 1/3 of the crown of the tooth; 4= Plaque covering at least 1/3 but less than 2/3 of the crown of the tooth; 5= Plaque covering 2/3 or more of the crown of the tooth. | 6, 12 and 24 weeks | 
| Bacterial Count at Baseline, After 6, 12, 24 and 32 Weeks | Microbiological samples were collected at baseline, 6 weeks, 12 weeks, 24 weeks and 32 weeks. Plaque was harvested from contra-lateral 1st molar teeth, where no restorations are present, using a sterile paper point. The paper point was immersed into 4 ml of Calgon Ringer's solution in a sterile bijou and kept on ice until they can be taken to the laboratory for processing (within 24 hours). | Baseline, 6, 12, 24 and 32 weeks |