Periodontal Infection and Endothelial Dysfunction

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of periodontal therapy on endothelial function and other biomarkers of cardiovascular disease

Detailed Description
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Periodontitis is one of the most prevalent chronic diseases and a frequent cause of tooth loss. Accumulation of subgingival dental biofilm in susceptible individuals is associated with an inflammatory host response characterized by the production of Matrix Metalloproteinases, reduction in collagen synthesis, increase in cytokine gene expression, and apoptosis of gingival fibroblasts. Finally, inflammation leads to destruction of periodontal ligament, alveolar bone resorption, and chronic periodontitis. Periodontitis is associated with increased serum levels of inflammatory cytokines and acute phase reactants. Multiple case-control and cohort studies have suggested that periodontitis is an independent risk factor for cardiovascular events, diabetic end-organ damage, pregnancy complications and respiratory diseases. Recent interventional studies have found that periodontal therapy could increase endothelium-dependent brachial artery flow-mediated dilation. The purpose of this controlled clinical trial is to determine the effect of periodontal therapy on endothelial function in subjects with moderate to severe chronic periodontitis. Furthermore, the relationship between putative periodontal pathogens and endothelial function will be also evaluated.

Official Title
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Impact of Periodontal Therapy on Endothelial Function

Conditions
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Periodontitis

Intervention / Treatment
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* Procedure: One-Stage Full-Mouth Disinfection
* Procedure: Periodontal care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be 25 years of age or older Three or more periodontal pockets with a probing depth (PD) > 5mm Have at least 20 natural teeth Provide informed consent and willingness to cooperate with the study protocol Exclusion Criteria: History of antibiotic use in the previous three months Pregnant or lactating females Treatment with antihypertensive, antilipemic, antiarrhythmic, and other cardiovascular drugs Systemic diseases such as diabetes, HIV/AIDS, liver disease, chronic renal failure, tuberculosis, and autoimmune diseases Previous history of cardiovascular disease: Acute myocardial infarct, stable angina, unstable angina, heart failure, atrial fibrillation, atrioventricular block, peripheral vascular disease, cerebrovascular accident Patients who received periodontal treatment within the last 3 months Patients who require antibiotic prophylaxis before examination or treatment Patients with mental retardation and dementia

Ages Eligible for Study
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Minimum Age: 25 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: One-Stage Full-Mouth Disinfection<br>Scaling and root planing, four quadrants in one session Tongue brushing with a 1% chlorhexidine gel (1 minute) Mouth rinsing with a 0.2% chlorhexidine solution for (2 minutes) Subgingival chlorhexidine (1%) irrigation in all pockets Twice daily rinsing with clorhexidine (1 minute) during fourteen days after the periodontal intervention Basic oral hygiene instructions Dental extractions will be performed at the end of patient followup (only in cases of teeth that could not be saved) | Procedure: One-Stage Full-Mouth Disinfection<br>* Scaling and root planing, four quadrants in one session Tongue brushing with a 1% chlorhexidine gel (1 minute) Mouth rinsing with a 0.2% chlorhexidine solution for (2 minutes) Subgingival chlorhexidine (1%) irrigation in all pockets Twice daily rinsing with clorhexidine (1 minute) during fourteen days after the periodontal intervention Basic oral hygiene instructions Dental extractions will be performed at the end of patient followup (only in cases of teeth that could not be saved)<br>|
| Active Comparator: Periodontal care<br>Basic oral hygiene instructions Supragingival plaque removal | Procedure: Periodontal care<br>* Basic oral hygiene instructions Supragingival plaque removal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Flow-mediated Dilation | All the assessments of vascular function were performed in the morning, in a temperature controlled room, with participants required to fast for at least 8 hours. Flow-mediated, endothelium dependent vasodilatation of the brachial artery (FMD) was measured using the technique described by Celermajer et al. using the guidelines reported by Coretti et al. FMD was calculated as the percentage of change in the diameter of brachial artery measured 45-60 s after cuff release in relation to the baseline measure (FMD%). | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High-sensitivity C-Reactive Protein | The fasting plasma hs-CRP concentrations was evaluated using a quantitative solid-phase, chemiluminescent immunometric assay (Immulite 1000, Siemens). | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | 
| Total Cholesterol |  | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | 
| White Blood Cell Count |  | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | 
| Subgingival Microbiota | Polymerase chain reaction (PCR) was used for detection of the three red-complex periodontal pathogens in periodontal pockets: Porphyromonas gingivalis (Pg), Treponema denticola (Td) and Tannerella forsythia (Tf). | 12 weeks post-periodontal therapy | 
| LDL Cholesterol |  | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | 
| Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin) | Multiplexed immuno-cytometric assay for the simultaneous measurement of MMP-9, MPO, tPAI-1, E-Selectin, ICAM-1, and VCAM-1 in serum samples (Milliplex® MAP kit, Human Cardiovascular Disease Panel 1, Millipore®). Luminex® 200™ IS Total System and xPONENT software were used for data acquisition and analysis. | 12 weeks post periodontal therapy | 
| Intercellular Adhesion Molecule 1 (ICAM-1) |  | 12 weeks post periodontal therapy | 
| Vascular Cell Adhesion Molecule 1 (VCAM-1) |  | 12 weeks post periodontal therapy | 
| Myeloperoxidase (MPO) |  | 12 weeks post periodontal therapy | 
| Matrix Metalloproteinase-9 (MMP-9) |  | 12 weeks post periodontal therapy | 
| Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) |  | 12 weeks post periodontal therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Periodontitis, Oral health, Cardiovascular disease