Impact of Treating Severe Periodontitis on Inflammatory Activity of Atheromatous Plaques in Patients With Acute Myocardial Infarction (AMI)

Acute Myocardial Infarction Clinical Trial

— PAROCARD  

Official title:

Impact of Treating Severe Periodontitis on Inflammatory Activity of Atheromatous Plaques in Patients With Acute Myocardial Infarction (AMI)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04046237
• Other study ID #: P 171104
• Status: Recruiting
• Phase: N/A
• Start date: August 2, 2019
• Est. completion date: December 2024

Study information

• Verified date: March 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Philippe Gabriel STEG
• Phone: 01 40 25 80 80
• Email: gabriel.steg[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicenter randomized clinical trial with two arms in patients hospitalized for an AMI nested in the Frenchie registry. Periodontal therapy is performed by periodontists in the intervention group versus treatment by dental surgeons as part of their usual practice in the control group.

For the intervention group, periodontal management will be carried out for a maximum of 6 months after randomisation, prolonged by a follow-up of 6 months including a maintenance visit at M9.

All patients will have an FDG-PET at M0 and M12 for evaluation of inflammation on carotid atherosclerotic plaques.

Description:

Eligible adults 30 to 70 years old hospitalized for an MI, (cf inclusion and non-inclusion criteria), will be asked to participate in the study. (screening)

At M0 :

• patients will be examined by a periodontist for assessing the severity of periodontitis (standard oral examination including a periodontal screening test).

• Patients with severe periodontitis will then receive: Complete periodontal examination of all teeth (6 sites per tooth) including pocket depth measurement, measurement of gingival recession, plaque index, gingival bleeding index, and a gingival fluid sample. Patients will then be informed of their periodontal status and therapeutic options. At this point, the patient may decide not to follow the treatment and will not be randomized.

• Patients who agree to continue the study will have a venous blood sample and a PET-FDG examination. Patients in whom the acquisition of FDG-PET is impossible will not be randomized.

At the end of these examinations, if all the conditions are met, the randomization will be carried out :

• Intervention group: Periodontal treatment, for a maximum of 6 months. At the end of the periodontal treatment, a follow-up of at least 6 months, including a maintenance visit to M9, will be performed.

• Control group: patients will be referred to their treating dentist for usual care.

At M12 : All patients (intervention group and control group) will have the same tests as M0

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: December 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients hospitalized for an acute myocardial infarction and included in the Frenchie registry

• Score = 5 on the screening questionnaire for periodontitis

• Six teeth at least (excluding wisdom teeth)

• Consent signature

• Affiliation to a French medical insurance (Sécurité Sociale)

Exclusion Criteria:

• Patients with diseases,other than cardiovascular and diabetes, known to change the periodontal state such as AIDS, rheumatoid arthritis, Chediak-Higashi syndrome, Papillon-Lefèvre

• Systemic antibiotic therapy> 48 hours in the 3 months prior to inclusion

• Acute heart failure

• Uncontrolled ventricular rhythm disorders

• Impossibility for the patient to attend follow-up visits

• Impossibility to maintain the extended position for 20 minutes

• Immunosuppressive therapy> 1 month in the 6 months prior to inclusion

• Pregnancy, breastfeeding

• Known hypersensitivity to chlorhexidine, povidone, 18-fluoro-deoxyglucose

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Atherosclerosis
• Carotid Artery Diseases
• Carotid Atherosclerosis
• Infarction
• Myocardial Infarction
• Periodontitis
• Plaque, Atherosclerotic
• Severe Periodontitis

Intervention

Other:
• Periodontal treatment
Periodontal treatment can last up to 6 months depending on the periodontal state, followed by a follow-up period of at least 6 months including a visit to M9. Briefly, the intervention group includes initial therapy in 48 hours maximum which includes information on oral hygiene techniques (verbal + brochure), scaling and surfacing of dental roots with antiseptic irrigation and non-tooth extraction. retainable. This initial therapy is followed by a resumption of periodontal clinical measures after 6 weeks. Depending on the degree of improvement of the measurements, the treatment is either completed, or continues with further scaling-surfacing and / or performing one or more periodontal surgeries. Periodontal monitoring period often called "maintenance" includes repeated sessions of simple scaling whose rate does not exceed 4 per year.

Locations

Country	Name	City	State
France	Hôpital Bichat, AP-HP	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	National Research Agency, France

Country where clinical trial is conducted

France, 

References & Publications (23)

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Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, Taylor GW, Page RC, Beck JD, Genco RJ. Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015 May;86(5):611-22. doi: 10.1902/jop.2015.140520. Epub 2015 Feb 17. — View Citation

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Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res. 2014 Nov;93(11):1045-53. doi: 10.1177/0022034514552491. Epub 2014 Sep 26. Review. — View Citation

LaMonte MJ, Genco RJ, Hovey KM, Wallace RB, Freudenheim JL, Michaud DS, Mai X, Tinker LF, Salazar CR, Andrews CA, Li W, Eaton CB, Martin LW, Wactawski-Wende J. History of Periodontitis Diagnosis and Edentulism as Predictors of Cardiovascular Disease, Stroke, and Mortality in Postmenopausal Women. J Am Heart Assoc. 2017 Mar 29;6(4). pii: e004518. doi: 10.1161/JAHA.116.004518. — View Citation

Lockhart PB, Bolger AF, Papapanou PN, Osinbowale O, Trevisan M, Levison ME, Taubert KA, Newburger JW, Gornik HL, Gewitz MH, Wilson WR, Smith SC Jr, Baddour LM; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation. 2012 May 22;125(20):2520-44. doi: 10.1161/CIR.0b013e31825719f3. Epub 2012 Apr 18. — View Citation

Meuric V, Le Gall-David S, Boyer E, Acuña-Amador L, Martin B, Fong SB, Barloy-Hubler F, Bonnaure-Mallet M. Signature of Microbial Dysbiosis in Periodontitis. Appl Environ Microbiol. 2017 Jun 30;83(14). pii: e00462-17. doi: 10.1128/AEM.00462-17. Print 2017 Jul 15. — View Citation

Offenbacher S, Beck JD, Moss K, Mendoza L, Paquette DW, Barrow DA, Couper DJ, Stewart DD, Falkner KL, Graham SP, Grossi S, Gunsolley JC, Madden T, Maupome G, Trevisan M, Van Dyke TE, Genco RJ. Results from the Periodontitis and Vascular Events (PAVE) Study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease. J Periodontol. 2009 Feb;80(2):190-201. doi: 10.1902/jop.2009.080007 . — View Citation

Pessi T, Karhunen V, Karjalainen PP, Ylitalo A, Airaksinen JK, Niemi M, Pietila M, Lounatmaa K, Haapaniemi T, Lehtimäki T, Laaksonen R, Karhunen PJ, Mikkelsson J. Bacterial signatures in thrombus aspirates of patients with myocardial infarction. Circulation. 2013 Mar 19;127(11):1219-28, e1-6. doi: 10.1161/CIRCULATIONAHA.112.001254. Epub 2013 Feb 15. — View Citation

Piconi S, Trabattoni D, Luraghi C, Perilli E, Borelli M, Pacei M, Rizzardini G, Lattuada A, Bray DH, Catalano M, Sparaco A, Clerici M. Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness. FASEB J. 2009 Apr;23(4):1196-204. doi: 10.1096/fj.08-119578. Epub 2008 Dec 12. — View Citation

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Reyes L, Herrera D, Kozarov E, Roldán S, Progulske-Fox A. Periodontal bacterial invasion and infection: contribution to atherosclerotic pathology. J Clin Periodontol. 2013 Apr;40 Suppl 14:S30-50. doi: 10.1111/jcpe.12079. Review. — View Citation

Rudd JH, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, Fuster V, Fayad ZA. (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007 Aug 28;50(9):892-6. Epub 2007 Aug 13. — View Citation

Salminen A, Gursoy UK, Paju S, Hyvärinen K, Mäntylä P, Buhlin K, Könönen E, Nieminen MS, Sorsa T, Sinisalo J, Pussinen PJ. Salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis. J Clin Periodontol. 2014 May;41(5):442-50. doi: 10.1111/jcpe.12234. Epub 2014 Feb 17. — View Citation

Schmitt A, Carra MC, Boutouyrie P, Bouchard P. Periodontitis and arterial stiffness: a systematic review and meta-analysis. J Clin Periodontol. 2015 Nov;42(11):977-87. doi: 10.1111/jcpe.12467. Epub 2015 Nov 24. Review. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of treatment of severe periodontitis in patients with an AMI	The primary endpoint will be the absolute difference of the Most-Diseased Segment (MDS) -Target to Background Ratio (TBR) measured at the segment with the highest activity on carotid arteries between the initial PET scan and the PET scan performed at 12 months after randomization	12 months after randomization
Secondary	Effect of treatment of severe periodontitis in patients with an AMI	Relative difference of the most-diseased segment (MDS) Tissue to Background ratio (TBR) ((M12-M0)/M0) of the Most-Diseased Segment (MDS) -Target to Background Ratio (TBR) measured at the segment with the highest activity	12 months after randomization
Secondary	Impact of periodontitis treatment on the intensity of global inflammatory activity measured in the alveolar bone	Relative ((M12-M0)/M0) and absolute (M12-M0) differences of TBR in the alveolar bone	12 months after randomization
Secondary	Impact of periodontitis treatment on the intensity of global inflammatory activity measured in the thoracic aorta	Relative ((M12-M0)/M0) and absolute (M12-M0) differences of mean TBR in the thoracic aorta	12 months after randomization
Secondary	Dysbiosis	Changes in the dysbiosis index	12 months after randomization
Secondary	CD31 in plasma and gingival fluid	Changes in concentrations of soluble CD31 in plasma and the gingival fluid	12 months after randomization
Secondary	Inflammatory markers concentrations in the gingival fluid and in the plasma	Changes in the inflammatory markers including IL-1ß, IL-6, IL-8, TNFalpha, MMP8, MMP9 concentrations in the gingival fluid and in the plasma	12 months after randomization
Secondary	Evaluation of overall inflammation in vascular arteries	Correlation between soluble CD31 / cleaved CD31 ratio and TBR	At randomization
Secondary	Evaluation of TBR measurments according to glycemia values	Evaluation of TBR measurments according to glycemia values measured prior to FDG-PET	12 months after randomization