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Correlation Between Oral Health and Systemic Inflammation (COHESION) (COHESION)

Primary Purpose

Inflammation, Periodontal Disease, Gingivitis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Plaque disclosing toothpaste
Non-plaque disclosing toothpaste
Sponsored by
Marshfield Clinic Research Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Inflammation focused on measuring Toothpaste, Inflammation, Periodontal Disease, hsCRP, Oral health, Oral hygiene

Eligibility Criteria

21 Years - 84 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Willing and able to provide written informed consent
  • Speak and understand English
  • Willing and able to comply with all procedures for the duration of the trial
  • ≥ 12 natural teeth
  • Baseline hs-CRP level ≥0.5 and ≤10.0 mg/L
  • No exposure to statins
  • Presence of dental provider assessed gingivitis or mild, moderate or severe periodontitis based on the American Academy of Periodontology (AAP) and presence of visible plaque/calculus

Exclusion Criteria:

  • Diagnosis or history of atherosclerosis, myocardial infarction, stroke, transient ischemic attack, peripheral vascular disease
  • History of inflammatory conditions such as rheumatoid arthritis, lupus or other chronic inflammatory condition; cancer
  • Exposure to statins
  • Consistent or prescribed use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS) or immunosuppressive drugs (defined as 10 or more doses in past 30 days)
  • Removable appliances only if gum inflammation is present where the appliance is seated
  • Dental prophylaxis [e.g., cleaning, scaling or root planning to mechanically remove plaque and calculus] within 30 days of randomization
  • Infection anywhere in the body 2 weeks prior to baseline visit (excluding presence of PD) or exposure to antibiotics or anti-viral agents during this time frame
  • Trauma to oral cavity within two weeks of baseline visit
  • Current tobacco use
  • Women who are pregnant or breast-feeding
  • Use of any investigational products within 30 days of randomization
  • History of allergies to dyes
  • Deemed not suitable for study participation based on the clinical judgment of the investigator

Sites / Locations

  • Marshfield Clinic-Marshfield Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Plaque disclosing toothpaste

Non-plaque disclosing toothpaste

Arm Description

Based on a randomization schema, a 30 day supply of the plaque disclosing toothpaste will be distributed to the participant. Participants will be instructed to brush two times a day for 30 days with the plaque disclosing toothpaste; avoiding the use of mouth rinses and floss. They will also be instructed to avoid any dental prophylaxis (e.g., cleaning, scaling or root planing to mechanically remove plaque and calculus) while on the trial and 30 days before they are enrolled.

Based on a randomization schema, a 30 day supply of the over-the-counter, non-plaque disclosing toothpaste will be distributed to the participant. Participants will be instructed to brush two times a day for 30 days with the plaque disclosing toothpaste; avoiding the use of mouth rinses and floss. They will also be instructed to avoid any dental prophylaxis (e.g., cleaning, scaling or root planing to mechanically remove plaque and calculus) while on the trial and 30 days before they are enrolled.

Outcomes

Primary Outcome Measures

Change in hsCRP levels with the use of the assigned toothpaste.
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.

Secondary Outcome Measures

Bleeding on Probing (BOP
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).
Periodontal Pocket Depth (PPD)
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.
Plaque Levels
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).
Overall oral health assessment and analytical plan
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.
Evaluate CD4/CD8 ratio for participants over the age of 45
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.

Full Information

First Posted
June 26, 2018
Last Updated
February 19, 2020
Sponsor
Marshfield Clinic Research Foundation
Collaborators
University of Wisconsin, Madison
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1. Study Identification

Unique Protocol Identification Number
NCT03641989
Brief Title
Correlation Between Oral Health and Systemic Inflammation (COHESION)
Acronym
COHESION
Official Title
Correlation Between Oral Health and Systemic Inflammation (COHESION)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
September 17, 2018 (Actual)
Primary Completion Date
December 30, 2019 (Actual)
Study Completion Date
December 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Marshfield Clinic Research Foundation
Collaborators
University of Wisconsin, Madison

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
COHESION is a randomized trial targeting reduction of systemic inflammation through an oral hygiene regimen incorporating a plaque-disclosing toothpaste and a control toothpaste.
Detailed Description
The present pilot trial will test the hypothesis that regular brushing with Plaque HD (interventional toothpaste) compared to conventional toothpaste (control) for 30 days in participants with confirmed mild to severe PD will significantly reduce hsCRP levels, a sensitive marker of inflammation and predictor of CVD. By completing the COHESION trial, we will collect important and relevant data to support application for investigator-initiated research funding from the US National Institutes of Health to directly test whether Plaque HD reduces CVD in larger, scaled multi-center randomized trial. Participants will be asked to participate in three visits. During Visit One, we will be reviewing their medical and dental information as well as performing an oral evaluation to determine their level of gingivitis or periodontal disease. If the participant remains eligible, their blood will be drawn to determine whether the baseline hsCRP level falls within the eligible range (≥0.5 to ≤10.0 mg/L). During Visit Two, if the participant remains eligible, they will be randomized and given a 30-day supply of the interventional or control toothpaste along with a study diary to track their progress. The participant will receive a follow-up call 15 days after Visit Two to track compliance with study activity and monitor for any adverse events. 30-days later, during Visit Three, the participants will undergo another oral evaluation in addition to a second blood draw to measure the hsCRP level after using their assigned toothpaste for 30 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation, Periodontal Disease, Gingivitis
Keywords
Toothpaste, Inflammation, Periodontal Disease, hsCRP, Oral health, Oral hygiene

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized to brush twice daily for 30 days with the plaque disclosing agent toothpaste or a reference, non-plaque disclosing toothpaste. Toothpastes are comparable based on equivalent content of the active ingredient: fluoride.
Masking
Participant
Masking Description
Participants will not be told which toothpaste they have been given.
Allocation
Randomized
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Plaque disclosing toothpaste
Arm Type
Active Comparator
Arm Description
Based on a randomization schema, a 30 day supply of the plaque disclosing toothpaste will be distributed to the participant. Participants will be instructed to brush two times a day for 30 days with the plaque disclosing toothpaste; avoiding the use of mouth rinses and floss. They will also be instructed to avoid any dental prophylaxis (e.g., cleaning, scaling or root planing to mechanically remove plaque and calculus) while on the trial and 30 days before they are enrolled.
Arm Title
Non-plaque disclosing toothpaste
Arm Type
Placebo Comparator
Arm Description
Based on a randomization schema, a 30 day supply of the over-the-counter, non-plaque disclosing toothpaste will be distributed to the participant. Participants will be instructed to brush two times a day for 30 days with the plaque disclosing toothpaste; avoiding the use of mouth rinses and floss. They will also be instructed to avoid any dental prophylaxis (e.g., cleaning, scaling or root planing to mechanically remove plaque and calculus) while on the trial and 30 days before they are enrolled.
Intervention Type
Other
Intervention Name(s)
Plaque disclosing toothpaste
Intervention Description
Plaque identifying toothpaste with a FDA-registered seed-extract dye (Annatto (Bixa Orellana)) and FD&C Blue No. 1.
Intervention Type
Other
Intervention Name(s)
Non-plaque disclosing toothpaste
Intervention Description
Toothpaste that does not contain the FDA-registered seed-extract dye (Annatto (Bixa Orellana)) and FD&C Blue No. 1.
Primary Outcome Measure Information:
Title
Change in hsCRP levels with the use of the assigned toothpaste.
Description
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.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Bleeding on Probing (BOP
Description
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).
Time Frame
30 days
Title
Periodontal Pocket Depth (PPD)
Description
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.
Time Frame
30 days
Title
Plaque Levels
Description
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).
Time Frame
30 days
Title
Overall oral health assessment and analytical plan
Description
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.
Time Frame
30 days
Title
Evaluate CD4/CD8 ratio for participants over the age of 45
Description
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.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
84 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Willing and able to provide written informed consent Speak and understand English Willing and able to comply with all procedures for the duration of the trial ≥ 12 natural teeth Baseline hs-CRP level ≥0.5 and ≤10.0 mg/L No exposure to statins Presence of dental provider assessed gingivitis or mild, moderate or severe periodontitis based on the American Academy of Periodontology (AAP) and presence of visible plaque/calculus Exclusion Criteria: Diagnosis or history of atherosclerosis, myocardial infarction, stroke, transient ischemic attack, peripheral vascular disease History of inflammatory conditions such as rheumatoid arthritis, lupus or other chronic inflammatory condition; cancer Exposure to statins Consistent or prescribed use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS) or immunosuppressive drugs (defined as 10 or more doses in past 30 days) Removable appliances only if gum inflammation is present where the appliance is seated Dental prophylaxis [e.g., cleaning, scaling or root planning to mechanically remove plaque and calculus] within 30 days of randomization Infection anywhere in the body 2 weeks prior to baseline visit (excluding presence of PD) or exposure to antibiotics or anti-viral agents during this time frame Trauma to oral cavity within two weeks of baseline visit Current tobacco use Women who are pregnant or breast-feeding Use of any investigational products within 30 days of randomization History of allergies to dyes Deemed not suitable for study participation based on the clinical judgment of the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Acharya, BDS, MS, PhD
Organizational Affiliation
Marshfield Clinic Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marshfield Clinic-Marshfield Center
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States

12. IPD Sharing Statement

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25688694
Citation
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Description
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https://www.salimetrics.com/saliva-collection-handbook/
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Correlation Between Oral Health and Systemic Inflammation (COHESION)

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