Periodontal and Cardiovascular Diseases Project

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

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.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Periodontitis
• Intervention / Treatment: Procedure: Scaling and root planing; Procedure: Supragingival prophylaxis

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Faculty of dentistry, Complutense University Madrid
  • Madrid
    • Leganes, Madrid, Spain
      • Severo Ochoa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Scaling and root planing; Two sessions of scaling and root planing under local anesthesia and oral antiseptics (clorhexidine 0.12% rinse),	Procedure: Scaling and root planing; Two sessions of scaling and root planing under local anesthesia and clorhexidine rinse twice/day, 15 days; Other Names: Clorhexidine rinse (0.12%) (Perio-Aid, Dentaid, Spain)
Placebo Comparator: Supragingival prophylaxis; Two sessions of supragingival prophylaxis under local anesthesia and an oral rinse with no antiseptic properties.	Procedure: Supragingival prophylaxis; Two sessions of scaling and root planing under local anesthesia and sodium fluoride rinse, twice/day, 15 days; Other Names: Sodium fluoride rinse (Fluor-Aid, Dentaid, Spain)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Mariano Sanz, Professor, Faculty of Dentistry, Complutense University of Madrid; Principal Investigator: David Herrera, Professor, Faculty of Dentistry, Complutense University of Madrid; Study Director: Elena Figuero, Professor, Faculty of Dentistry, Complutense University of Madrid; Study Chair: María Molina, Doctor, Servicio de Cardiología, Hospital Universitario Severo Ochoa

Publications and helpful links

General Publications

• Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J. Treatment of periodontitis and endothelial function. N Engl J Med. 2007 Mar 1;356(9):911-20. doi: 10.1056/NEJMoa063186. Erratum In: N Engl J Med. 2018 Jun 13;:null.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2016
• Primary Completion (Actual): February 19, 2020
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: March 17, 2016
• First Submitted That Met QC Criteria: March 17, 2016
• First Posted (Estimated): March 23, 2016

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Bacteremia; Periodontitis; Cardiovascular diseases; Scaling and root planing; carotid intima-media thickness; Porphyromonas gingivalis; Flow-mediated dilation; Aggregatibacter actinomycetemcomitans
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Cardiovascular Diseases; Periodontitis; Physiological Effects of Drugs; Protective Agents; Cariostatic Agents; Fluorides; Sodium Fluoride
• Other Study ID Numbers: 14/120-E_BS; PI11/00542 (Other Grant/Funding Number: Instituto de Salud Carlos III)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED