Ertugliflozin: Cardioprotective Effects on Epicardial Fat

The purpose of this study is to learn if Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) medications enhance beneficial properties of epicardial adipose tissue including metabolic flexibility, insulin sensitivity, decreased cell size and reduced inflammation.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Atherosclerosis; Insulin Resistance; Type 2 Diabetes
• Intervention / Treatment: Drug: Ertugliflozin; Drug: Glipizide

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Ekrem M Ayhan, BS; Phone Number: (908) 619-5381; Email: ayhane@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patient at Stanford Cardiovascular Surgery clinic who is scheduled for cardiac bypass surgery
• history of Diabetes Mellitus Type 2 currently taking metformin or diet-controlled

Exclusion Criteria:

• allergy or intolerance to interventional medication
• currently taking any anti-diabetic medication other than metformin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ertugliflozin; Ertugliflozin, also known as Steglatro, will be administered once daily for 5 days at a dose of 15mg orally.	Drug: Ertugliflozin; Consenting participants in the Ertugliflozen group will be supplied with 2-week course of medication prior to cardiac surgery. Participants will be educated on use and have blood glucose monitored during the medication course. The surgeon will then collect a small amount of fat near the heart during surgery.; Other Names: SGLT2 inhibitor
Active Comparator: Glipizide; Glipizide will be randomized to either 2.5mg or 5mg oral dose once daily for 5 days.	Drug: Glipizide; Consenting participants in the Glipizide group will be supplied with 2-week course of medication prior to cardiac surgery. Participants will be educated on use and have blood glucose monitored during the medication course. The surgeon will then collect a small amount of fat near the heart during surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of isoproterenol-stimulated lipolysis to measure metabolic flexibility in epicardial adipose tissue samples.	Analysis will be performed using Lipolysis Colorimetric Assay and measured by glycerol content on standard curve. Indirect effects of SGLT2i in vivo in epicardial adipose tissue will be compared to Glipizide by measuring rate of lipolysis, or breakdown of adipose in to free fatty acids.	Time to collect tissue collected during surgery (up to 15 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average insulin mediated glucose uptake (IMGU) to measure insulin sensitivity in epicardial adipose tissue samples.	Mature adipocytes will be isolated, cultured, and treated with 2-NBDG, a fluorescently-labeled deoxyglucose analog, as a probe for the detection of glucose uptake measured by excitation/emission of florescence in the mature cells.	Time to collect tissue collected during surgery (up to 15 minutes)
Characterization of the inflammatory cytokine expression profile in epicardial adipose tissue samples.	Analysis will be performed using Luminex to measure levels of inflammatory cytokines on the human adipocyte panel.	Time to collect tissue collected during surgery (up to 15 minutes)
Distribution of adipose cell size in epicardial tissue.	After tissue collection and osmium fixation, adipose cell size will be determined by Beckman Coulter Multisizer III, and described via a mathematical model to estimate peak diameter, fat storage capacity, size variability, and % small cells.	Time to collect tissue collected during surgery (up to 15 minutes)

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Tracey McLaughlin, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: SGLT2 Inhibitor; Epicardial Adipose Tissue
• Additional Relevant MeSH Terms: Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Hyperinsulinism; Cardiovascular Diseases; Insulin Resistance; Atherosclerosis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Glipizide; Ertugliflozin; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: 52647

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