Ertugliflozin: Cardioprotective Effects on Epicardial Fat

Early Phase 1

Completed

• Conditions: Cardiovascular Diseases; Atherosclerosis; Type 2 Diabetes; Insulin Resistance
• Interventions: Drug: Ertugliflozin

• Registration Number: NCT04167761
• Lead Sponsor: Stanford University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-15
• Study First Submitted QC: 2019-11-15
• Study First Posted: 2019-11-19
• Study Start: 2020-07-01
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-17
• Last Update Posted: 2024-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

• patient at Stanford Cardiovascular Surgery clinic who is scheduled for cardiac bypass surgery or vascular surgery
• history of Diabetes Mellitus Type 2 currently diet controlled, or on metformin or dpp4 inhibitors

Exclusion Criteria

• allergy or intolerance to interventional medication
• currently taking insulin, glp-1 inhibitors, or sulfonylureas

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ertugliflozin (treated tissue)	Ertugliflozin	Adipose tissue samples collected from participants were treated with Ertugliflozin at a concentration of 25 µM in vitro. Tissue samples were incubated with Ertugliflozin to evaluate its effects on lipolysis, inflammation, and gene expression in epicardial, pericardial, and subcutaneous adipose tissues

Primary Outcome Measures

Name	Time	Method
Rate of isoproterenol-stimulated lipolysis to measure metabolic flexibility in epicardial adipose tissue samples.	Time to collect tissue collected during surgery (up to 15 minutes)	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.

Secondary Outcome Measures

Name	Time	Method
Average insulin mediated glucose uptake (IMGU) to measure insulin sensitivity in epicardial adipose tissue samples.	Time to collect tissue collected during surgery (up to 15 minutes)	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.
Characterization of the inflammatory cytokine expression profile in epicardial adipose tissue samples.	Time to collect tissue collected during surgery (up to 15 minutes)	Analysis will be performed using Luminex to measure levels of inflammatory cytokines on the human adipocyte panel.
Distribution of adipose cell size in epicardial tissue.	Time to collect tissue collected during surgery (up to 15 minutes)	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.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States