Epicardial Fat and Clinical Outcomes After Coronary Artery Bypass Grafting in Diabetics vs. Non Diabetics

NCT03360981 | Completed Phase 4

• 1 other identifier: 28.11.2017.1
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular disease (CVD) is a group of diseases including both the heart and blood vessels, thereby including coronary heart disease (CHD). To date, diabetics have a higher incidence and prevalence of multivessels CHD. Treatments in multivessels CHD in diabetics include full medical anti ischemic therapy, and revascularization therapy (Percutaneous coronary intervention (PCI) and/or Coronary artery bypass grafting (CABG)). Randomized trials comparing multivessel PCI to CABG have consistently demonstrated the superiority of CABG in reducing mortality, myocardial infarctions and need for repeat revascularizations. After the CABG treatment, diabetics vs. non-diabetics evidenced a worse prognosis, and an increased mortality. Numerous molecular, epigenetics (as microRNAs), and other metabolic risk factors may condition the worse prognosis in diabetics vs. non diabetics after CABG. In this context, an increased epicardial fat tissue thickness may be independently associated with the prevalence of diabetes, and diabetics have an higher epicardial fat tissue thickness, volumetry, and enhanced metabolism. Therefore, after CABG, lifestyle and medical improvements may lead to the reduction of epicardial fat thickness, extension, and metabolism in both non-diabetics, and diabetics, ameliorating the prognosis. At moment, epicardial tissue function in diabetics is not well investigated in literature, and no data has been reported about new hypoglycemic drugs, and its pleiotropic effects on diabetics after CABG. Indeed, our study hypothesis was that, epicardial fat tissue dimension, and metabolic activity may be related to a different expression of inflammatory, oxidative, and apoptotics molecules, and epigenetic effectors in diabetics vs. non-diabetics. Secondary, these effectors, and epicardial tissue dimension and activity, may be controlled, after CABG, by incretin treatment in diabetics. Therefore, incretin therapy may be associated to the reduction in epicardial fat tissue thickness, and extension, with down regulation of different inflammatory, oxidative and apoptotics molecules, and epigenetic effectors involved in epicardial fat metabolism. Moreover, in this study authors will evaluate in diabetics vs. non diabetics, and in diabetic incretin-users vs. never.-incretin-users, all cause mortality, cardiac mortality, and Major adverse cardiac events (MACE) after CABG in diabetics vs. non diabetics, and diabetic incretin-users (6 months of incretin therapy) vs. diabetic never-incretin-users. Authors will correlate these clinical endpoints to the study of the epicardial fat anatomy and metabolism before and after CABG, and to circulating inflammatory and pro-apoptotic markers, epigenetic effectors, and stem cells in diabetics vs. non diabetics, and diabetic incretin-users (6 months of incretin therapy) vs. diabetic never-incretin-users.

Conditions

Diabetes; Coronary Artery Disease

Outcome Measures

Primary Outcomes (3)

• All cause mortality

  Authors will evaluate all cause of mortality in in diabetics vs. non diabetics, and in diabetics incretin-users vs. never-incretin-users by hospital discharge schedules, deaths registry, and during follow up visits.

  12 months

• cardiac mortality

  Authors will evaluate cardiac mortality in in diabetics vs. non diabetics, and in diabetics incretin-users vs. never-incretin-users by hospital discharge schedules, deaths registry, and during follow up visits.

  12 months

• Major adverse cardiac events (MACE)

  Authors will evaluate MACE in in diabetics vs. non diabetics, and in diabetics incretin-users vs. never-incretin-users by hospital discharge schedules, hospitalization schedules, and during follow up visits.

  12 months

Secondary Outcomes (3)

• molecular markers (Sirtuin 1, 6, etc) to predict study endpoints

  12 months

• serum microRNAs and epicardial fat microRNAs,

  12 months

• stem cells isolated in epicardial fat.

  12 months

Study Arms (3)

diabetics incretin-users (arm 1)

ACTIVE COMPARATOR

epicardial tissue biopsy, and than treated by incretin therapy plus standard anti ischemic therapy.

Drug: Incretins

diabetics never-incretin-users (arm 2)

PLACEBO COMPARATOR

epicardial tissue biopsy, and than treated by standard hypoglycemic drug therapy plus standard anti ischemic therapy.

Drug: Incretins

non diabetics (arm 3)

NO INTERVENTION

non diabetics, treated by coronary artery bypass grafting (CABG), receiving epicardial tissue biopsy, and than treated by standard anti ischemic therapy.

Interventions

Incretins DRUG

after CABG, and epicardial tissue biopsy, patients will receive incretin therapy.

diabetics incretin-users (arm 1); diabetics never-incretin-users (arm 2)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients aged \>18, \<75, left ventricle ejection fraction (LVEF) \>50%, multivessel coronary disease detected by coronarography, indication to receive a CABG, stable CAD. All diabetics and non diabetics.

You may not qualify if:

• acute myocardial infarction, heart failure, neoplastic disease, chronic diseases that may affect the inflammatory profile both systemic and epicardial (cancer, chronic intestinal inflammation, hepatitis, AIDS); life expectancy \< 6 months, previous CABG and/or other open heart surgery intervention, acute coronary syndrome

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

Raffaele Marfella

Naples, Italy, 80128, Italy

Location

Related Publications (1)

• Sardu C, D'Onofrio N, Torella M, Portoghese M, Loreni F, Mureddu S, Signoriello G, Scisciola L, Barbieri M, Rizzo MR, Galdiero M, De Feo M, Balestrieri ML, Paolisso G, Marfella R. Pericoronary fat inflammation and Major Adverse Cardiac Events (MACE) in prediabetic patients with acute myocardial infarction: effects of metformin. Cardiovasc Diabetol. 2019 Sep 30;18(1):126. doi: 10.1186/s12933-019-0931-0.

  PMID: 31570103 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Coronary Artery Disease

Interventions

Incretins

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MSc, PhD

Model Details: arm 1 , diabetics treated by coronary artery bypass grafting (CABG), receiving epicardial tissue biopsy, and than treated by incretin therapy plus standard anti ischemic therapy.. arm 2, diabetics, treated by coronary artery bypass grafting (CABG), receiving epicardial tissue biopsy, and than treated by standard hypoglycemic drug therapy plus standard anti ischemic therapy. arm 3, non diabetics, treated by coronary artery bypass grafting (CABG), receiving epicardial tissue biopsy, and than treated by standard anti ischemic therapy.

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 4, 2017
• Study Start: September 20, 2017
• Primary Completion: November 20, 2017
• Study Completion: August 20, 2025
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

IT (1)