Correlation Between Oral Health and Systemic Inflammation (COHESION)

The primary outcome measure is magnitude of change in level of high sensitivity CRP (hsCRP) pre-trial compared to post trial as a surrogate marker to monitor change in local and systemic inflammation. Study eligible subjects with hsCRP levels between 0.5 and 10.0 mg/L at baseline (Visit 1) will be randomized to brushing for 30 days with one of two toothpastes followed by reassessment at visit 3 at the end of the intervention. Since distribution of hsCRP is skewed toward higher values, to satisfy statistical model assumptions, significance of the observed differences in outcomes between groups from baseline to day 30 will be tested on log-transformed data by using ANCOVA with treatment and baseline measurement as main factors and treatment by baseline measurement interaction. All significance tests for hsCRP will be conducted using R version 3.3.1 and two-sided significance levels of 0.05.

Decrease in number of teeth with BOP following tooth-brushing intervention from baseline visit is a represents a primary clinical indicator of reduction in local inflammation of periodontal tissue. BOP per tooth will be evaluated by a dental professional using a periodontal probe along the gum line of each tooth at 6 sites per tooth at the baseline pre-trial visit (Visit One) and at post trial Visit Three after the 30 day tooth brushing intervention. The outcome measure will be the difference in the number of teeth exhibiting BOP pre and post the 30 day trial. This variable has no units and is a dichotomous nominal variable (i.e yes/no) evaluated on a per-tooth basis across total number of evaluable teeth present in the participant's mouth. (Scoring: 1=BOP present; 0=BOP absent).

PPD per tooth at 6 sites per tooth as a measure of periodontal health at baseline pre and post use of the assigned toothpaste will be assessed to determine presence and extent of PD. A dental professional will perform a periodontal assessment, pre (Visit one) and post (Visit three) the 30 day tooth brushing intervention applying Periodontology (AAP) 1999 Classification Criteria with 2015 updates to classify extent of PD as a continuous variable. PPD measurement, measured in mm, will be carried out pre and post clinical trial participation using a periodontal probe.

Each evaluable tooth will be examined by a dental professional for presence of supra-gingival biofilm deposited by oral pathogens using a periodontal probe at the pre baseline visit (Visit One) and post (Visit Three) visit following the 30 day tooth brushing intervention. Number of teeth with a change in visible plaque deposits post-trial compared to pre-trial levels will be determined. This variable has no units and will be evaluated as a dichotomous nominal variable (i.e., yes/no) on a per-tooth basis across total number of evaluable teeth. (Scoring: 1=visible plaque present; 0= no visible plaque).

Analytical plan for secondary outcomes: Significance of any differences in oral health characteristics at baseline (pre) and post intervention will be tested by t-tests for continuous and chi-square tests for discrete variables. For parameter estimation, means and mean ratios will calculated for each treatment group at each time point along with standard deviations. The purpose of collection of overall oral health assessment is to inform on the relative health of the participants mouth at time zero to support conduct of a sub-analysis to determine whether the magnitude of change in hsCRP correlated with relative health of the mouth determined during the pre-trial oral health assessment.

CD4/CD8 ratios will be measured in the subset of subjects who meet eligibility based on hsCRP measures but whose CD4/CD8 ratio is less than 1.2 following analysis of blood collected in visit 1. Subjects whose CD4/CD8 ratio fell below 1.2 in visit 1 will have reassessment of CD4/CD8 ratio done on blood collected in visit 3. The magnitude of change in CD4/CD8 pre and post-trial will be evaluated tested by t-test analysis for this continuous variable.