- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03260881
Liraglutide Effects on Epicardial Fat Inflammatory Genes
March 14, 2024 updated by: Gianluca Iacobellis, University of Miami
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.
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-α) and Interleukin 6 (IL-6), and GLP-1R.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
40
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Gianluca Iacobellis, MD PhD
- Phone Number: 3052433636
- Email: giacobellis@med.miami.edu
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- Recruiting
- University of Miami
-
Contact:
- Gianluca Iacobellis, MD PhD
- Phone Number: 305-243-3636
- Email: giacobellis@med.miami.edu
-
Principal Investigator:
- Gianluca Iacobellis, MD PhD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: L-group
• L-group will be started on liraglutide.
Liraglutide will be started and administered for from a minimum of 4 weeks up to 12 weeks prior to CABG with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg).
The dose of 1.8 mg daily will be maintained until the end of the 12-week study.
Other and current diabetes treatment will be continued
|
Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide, (L-group) or to remain on current treatment or placebo (D-group).
|
Placebo Comparator: D-group
placebo will be administered in addition to current treatment prior to the CABG with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg).
D-group 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.
|
Study subjects will be randomized in two groups of 20 patients to receive additional liraglutide, (L-group) or to remain on current treatment or placebo (D-group).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EAT inflammation
Time Frame: from a minimum of 4 weeks up to 12 weeks
|
EAT inflammation as measured by mRNA and protein expression of Tumor Necrosis Factor (TNF)-Alpha and Interleukin (IL)-6 from blood sample.
|
from a minimum of 4 weeks up to 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EAT thickness
Time Frame: from a minimum of 4 weeks up to 12 weeks
|
EAT thickness as measured via ultrasound
|
from a minimum of 4 weeks up to 12 weeks
|
SAT inflammation
Time Frame: from a minimum of 4 weeks up to 12 weeks
|
Subcutaneous Adipose Tissue (SAT) inflammation as measured by mRNA and protein expression of Tumor Necrosis Factor (TNF)-Alpha and Interleukin (IL)-6 from blood sample
|
from a minimum of 4 weeks up to 12 weeks
|
EAT GLP-1R
Time Frame: from a minimum of 4 weeks up to 12 weeks
|
EAT Glucagon-like Peptide-1 Receptor (GLP-1R) mRNA and protein expression from blood sample
|
from a minimum of 4 weeks up to 12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Gianluca Iacobellis, MD PhD, University of Miami
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 1, 2018
Primary Completion (Estimated)
June 30, 2024
Study Completion (Estimated)
June 30, 2024
Study Registration Dates
First Submitted
August 22, 2017
First Submitted That Met QC Criteria
August 22, 2017
First Posted (Actual)
August 24, 2017
Study Record Updates
Last Update Posted (Actual)
March 15, 2024
Last Update Submitted That Met QC Criteria
March 14, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Coronary Artery Disease
- Myocardial Ischemia
- Coronary Disease
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Incretins
- Glucagon-Like Peptide-1 Receptor Agonists
- Liraglutide
Other Study ID Numbers
- 20170684
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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