Liraglutide Effects on Epicardial Fat Inflammatory Genes

  • STATUS
    Recruiting
  • End date
    Jun 30, 2022
  • participants needed
    40
  • sponsor
    University of Miami
Updated on 8 March 2021
bypass graft
heart surgery
arterial disease

Summary

Epicardial adipose tissue (EAT) is the visceral fat of the heart. EAT could locally affect the coronary arteries through local secretion of pro-inflammatory cytokines. EAT plays a role in the development of the coronary artery disease (CAD). EAT is a highly enriched with genes involved in inflammation. Given its rapid metabolism and simple measurability, as first developed by Iacobellis, EAT serves as target for medications targeting the fat. Glucagon-like peptide-1 agonists (GLP-1A) are anti-diabetic medications with recently suggested cardio-protective properties. Liraglutide, a GLP-1A, has recently shown to reduce the cardiovascular risk. Iacobellis'group found that EAT thickness decreased by an unprecedented 36% after 12 weeks of treatment with liraglutide. Remarkably, Iacobellis'group found for the first time that human EAT express GLP-1 Receptor (GLP-1R). GLP-1A effects may be therefore visceral fat specific and target EAT. Based on these preliminary data, we hypothesize that treatment with liraglutide will significantly and rapidly reduce EAT inflammation. Decreased EAT inflammation can reduce the burden of the coronary plaques. We will test our hypothesis in a 12-week randomized, double-blind, placebo-controlled, interventional study in 40 patients with type 2 diabetes mellitus (T2DM), and CAD, with an acceptable glycemic control on their current diabetes regimen who require elective coronary artery bypass graft (CABG) regardless of their participation in the study. A minimum time frame of 4-week treatment will be considered to detect significant changes in the study endpoints. Inclusion criteria for body fat markers will rule out the confounding effect of different body fast distribution at baseline. Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide or to remain on current treatment/ placebo prior to cardiac surgery. CAD subjects not allocated to liraglutide will be started on a supervised low calorie diet (LCD) to achieve approximately 5% of weight loss after from a minimum of 4 weeks up to 12 weeks to avoid the confounding effect of weight loss on the study outcomes. EAT samples will be collected during cardiac surgery and processed for analysis of mRNA and protein expression of EAT inflammatory genes such as Tumor Necrosis Factor-alpha (TNF-) and Interleukin 6 (IL-6), and GLP-1R.

Details
Condition Coronary Artery Disease, Coronary heart disease, Type2 Diabetes, Cardiac Ischemia, Myocardial Ischemia
Treatment Liraglutide Pen Injector [Victoza], matching liraglutide-placebo pre-filled pens
Clinical Study IdentifierNCT03260881
SponsorUniversity of Miami
Last Modified on8 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Coronary heart disease or Coronary Artery Disease or Type2 Diabetes?
Do you have any of these conditions: Myocardial Ischemia or Cardiac Ischemia or Type2 Diabetes or Coronary heart disease or Coronary Artery Disease?
Do you have any of these conditions: Cardiac Ischemia or Coronary heart disease or Coronary Artery Disease or Myocardial Ischemia or Type2 Diabetes?
Do you have any of these conditions: Coronary Artery Disease or Cardiac Ischemia or Myocardial Ischemia or Coronary heart disease or Type2 Diabetes?
Do you have any of these conditions: Coronary Artery Disease or Type2 Diabetes or Cardiac Ischemia or Coronary heart disease or Myocardial Ischemia?
Do you have any of these conditions: Coronary heart disease or Myocardial Ischemia or Coronary Artery Disease or Cardiac Ischemia or Type2 Diabetes?
T2DM as defined by American Diabetes Association (ADA) criteria
Adult patients with T2DM who are indicated to receive liraglutide, not as first-line therapy, in addition to diet and exercise to improve glycemic control
Hemoglobin A1c (HbA1c) 9%
Age 18 years old
Body mass index (BMI) 27 Kg/m2 and/or waist circumference 102 cm (40 inches) in men and 88 cm (35 inches) in women, respectively
Clinically and angiographically stable CAD who requires CABG as part of the standard medical care, as CAD does not represent a contraindication for using liraglutide. The stability of the CAD further warranties that study patients will not be exposed to higher risk by using liraglutide

Exclusion Criteria

Patients with a personal or family history of medullary thyroid carcinoma or patients with Multiple Endocrine Neoplasia syndrome type 2
Patients with a prior serious hypersensitivity reaction to liraglutide
Other contra-indications to liraglutide in accordance with risks and safety information included in the latest updated prescribing information
Type 1 diabetes, as defined by ADA criteria
Current use of other GLP-1A, dipeptidyl peptidase 4 (DPP4) or Sodium Glucose transporters 2 (SGLT2) inhibitors, thiazolidinediones (TZDs), pramlintide and fixed prandial insulin
Patients with unstable CAD, assessed by the Cardiology team and defined as new onset angina, rest angina, rapidly increasing or crescendo angina
History of diabetic ketoacidosis, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy; acute or chronic infective diseases, cancer or chemotherapy, history of pulmonary, renal or liver diseases, and drug abuse
Patients with chronic and acute inflammatory conditions such as sepsis, rheumatoid arthritis, ectopic dermatitis, asthma, ulcerative colitis
Current use of systemic corticosteroids in the 3 months prior this study
Pregnant or breast-feeding women
Females of childbearing potential who are not using adequate contraceptive methods (as required by local law or practice)
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