Periodontal and Cardiovascular Diseases Project

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether basic periodontal therapy aim to reduce subgingival levels of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, has an impact on the vascular function of patients suffering from established cardiovascular disease.

Detailed Description
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Design: randomized clinical trial, parallel design, double blinded. Sample: 120 patients from the Cardiology Department of Hospital Severo Ochoa (Leganés, Madrid) suffering from established cardiovascular disease and generalized moderate/severe periodontitis. Sixty patients will be randomized to test group (scaling and root planing + systemic antimicrobials), and the other 60 subjects will be included in the control group, consisting on delayed periodontal treatment (supragingival prophylaxis + placebo). Study visits: Visit 1: screening Visit 2: baseline data collection (medical history, clinical variables, gingival crevicular fluid (GCF) samples, vascular function) Visit 3: panoramic x-ray, blood samples, randomization and first treatment session. Visit 4: second treatment session. Visit 5: 24 hours inflammatory biomarkers assessment. Visit 6: 7 days inflammatory biomarkers assessment. Visit 7: 1 month follow up (clinical variables) Visit 8: 3 months follow up (clinical variables, vascular function) and supportive periodontal therapy. Visit 9: 6 months follow up (clinical variables, GCF samples, inflammatory biomarkers, vascular function) and supportive periodontal therapy.

Official Title
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Impact of Basic Periodontal Therapy in the Levels of Porphyromonas Gingivalis and Aggregatibacter Actinomycetemcomitans Subgingival and Its Association With Vascular Function

Conditions
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Periodontitis, Cardiovascular Diseases

Intervention / Treatment
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* Procedure: Scaling and root planing
* Procedure: Supragingival prophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) patients with established cardiovascular disease (unstable angina or stroke in the previous 3 to 12 months, and left ventricular ejection fraction ≥50%); (2) diagnosis of moderate to severe generalized periodontitis (PD>5mm and marginal bone loss >30% on at least 50% of the teeth, according to Tonetti et al. 2007); (3) presence of at least 3 teeth per quadrant. Exclusion Criteria: (1) periodontal treatment in the previous year; (2) antibiotic intake in the previous 3 months; (3) smokers of ≥10 cigarettes per day; (4) pregnancy or breast feeding; (5) diabetes mellitus types I or II, with glycosylated hemoglobin values >7; (6) necrotizing periodontal diseases; (7) HIV infection; (8) chronic intake of NSAID
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: Scaling and root planing<br>Two sessions of scaling and root planing under local anesthesia and oral antiseptics (clorhexidine 0.12% rinse), | Procedure: Scaling and root planing<br>* Two sessions of scaling and root planing under local anesthesia and clorhexidine rinse twice/day, 15 days<br>* Other names: Clorhexidine rinse (0.12%) (Perio-Aid, Dentaid, Spain);|
| Placebo Comparator: Supragingival prophylaxis<br>Two sessions of supragingival prophylaxis under local anesthesia and an oral rinse with no antiseptic properties. | Procedure: Supragingival prophylaxis<br>* Two sessions of scaling and root planing under local anesthesia and sodium fluoride rinse, twice/day, 15 days<br>* Other names: Sodium fluoride rinse (Fluor-Aid, Dentaid, Spain);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow mediated dilation of the brachial artery | Endothelium-dependent vasodilatation of the brachial artery assessed by means of ultrasound imaging with the use of a 7-MHz linear probe and vessel diameter measurements. Dilatation was quantified as the change in percentage form a baseline measurement and a second measurement taken after 5 minutes of flow ischemia induced with a sphygmomanometer cuff placed on the forearm. | Day 0 (Baseline), Day 90, Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid artery atherosclerosis | Intima-media thickness of the carotid artery assessed by means of ultrasound imaging with the use of a 7-MHz linear probe and an automated imaging software. | Day 0 (Baseline), Day 90, Day 180 | 
| Periodontal pocket probing depth | Distance from the gingival margin to the base of the periodontal pocket, measured in 6 sites per tooth with a periodontal probe UNC-15. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Gingival recession | Distance from the gingival margin to the cementum-enamel junction, measured in 6 sites per tooth with a periodontal probe UNC-15. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Plaque index | Presence or absence of dental plaque around teeth, measured in 6 sites per tooth with a periodontal probe of the University of North Caroline (UNC)-15. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Bleeding on probing index | Presence or absence of bleeding 30 seconds after probing, measured in 6 sites per tooth with a periodontal probe UNC-15. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Suppuration on probing index | Presence or absence of gingival suppuration 30 seconds after probing, measured in 6 sites per tooth with a periodontal probe UNC-15. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Dental mobility | Presence of dental mobility, recorded according to Miller´s classification: 0: absence of mobility; 1: horizontal mobility <1mm; 2: horizontal mobility >1mm; 3: horizontal and vertical mobility. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Furcation lesions | Presence of periodontal attachment loss in the furcation area of multi-rooted teeth, recorded according to Lindhe´s classification: I: the probe penetrates less than one third of the horizontal dimension of the tooth; II: the probe penetrates more than one third of the horizontal dimension of the tooth; III: the probe penetrates through and through the tooth. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Number of present teeth | Number of teeth present in mouth. | Day 0 (baseline), Day 30, Day 90, Day 180 | 
| Radiographic bone loss | Percentage of bone loss around teeth measured in an orthopantomography (<30%, 30-50%, >50%). | Day 0 (baseline) | 
| Bacteria in gingival crevicular fluid | Total counts (CFU/ml) and percentage of the flora of anaerobic bacteria present in gingival crevicular fluid. Samples will be processed by means of culture and quantitative polymerase chain reaction | Day 0 (baseline), Day 180 | 
| Bacteria in blood samples | Total counts (CFU/ml) and percentage of the flora of anaerobic bacteria present in blood samples before and 10 minutes after the intervention. Samples will be processed by means of culture and quantitative polymerase chain reaction | Day 1 (pre and post-therapy) | 
| Inflammatory biomarkers in serum samples | Levels of inflammatory biomarkers (interleukin 6, C reactive protein, e-selectin) and coagulation factors (d-dimer, prothrombin, fibrinogen, Von Willebrand factor) in serum, assessed by means of Luminex technique (Bio-Plex Pro-Assays kit). | Day 1, Day 3, Day 10, Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Periodontitis, Cardiovascular diseases, Bacteremia, Scaling and root planing, Flow-mediated dilation, carotid intima-media thickness, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans