Liraglutide Effects on Epicardial Fat Inflammatory Genes
| Status: | Recruiting |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Diabetes |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 11/21/2018 |
| Start Date: | September 1, 2018 |
| End Date: | June 30, 2020 |
Effects of Liraglutide on Epicardial Fat Pro-Inflammatory Genes in Type 2 Diabetes and Coronary Artery Disease
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. Inclusion criteria
for body fat markers will rule out the confounding effect of different body fast distribution
at baseline. Interim fructosamine test will insure glycemic equipoise between study arms.
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 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-α) and Interleukin 6 (IL-6), and GLP-1R.
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. Inclusion criteria
for body fat markers will rule out the confounding effect of different body fast distribution
at baseline. Interim fructosamine test will insure glycemic equipoise between study arms.
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 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-α) and Interleukin 6 (IL-6), and GLP-1R.
Inclusion Criteria:
- 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)
We found this trial at
1
site
Miami, Florida 33124
(305) 284-2211
Principal Investigator: Gianluca Iacobellis, MD PhD
Phone: 305-243-3636
University of Miami A private research university with more than 15,000 students from around the...
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