Back to resultsErtugliflozin: Cardioprotective Effects on Epicardial Fat
Primary Purpose
Cardiovascular Diseases, Atherosclerosis, Type 2 Diabetes
Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ertugliflozin
Glipizide
Sponsored by
About this trial
This is an interventional basic science trial for Cardiovascular Diseases focused on measuring Epicardial Adipose Tissue, SGLT2 Inhibitor
Eligibility Criteria
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
Sites / Locations
- Stanford University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ertugliflozin
Glipizide
Arm Description
Ertugliflozin, also known as Steglatro, will be administered once daily for 5 days at a dose of 15mg orally.
Glipizide will be randomized to either 2.5mg or 5mg oral dose once daily for 5 days.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT04167761
First Posted
November 15, 2019
Last Updated
August 10, 2023
Sponsor
Stanford University
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT04167761
Brief Title
Ertugliflozin: Cardioprotective Effects on Epicardial Fat
Official Title
Ertugliflozin: Cardioprotective Effects on Epicardial Fat
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
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
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Atherosclerosis, Type 2 Diabetes, Insulin Resistance
Keywords
Epicardial Adipose Tissue, SGLT2 Inhibitor
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
unblinded randomized trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ertugliflozin
Arm Type
Experimental
Arm Description
Ertugliflozin, also known as Steglatro, will be administered once daily for 5 days at a dose of 15mg orally.
Arm Title
Glipizide
Arm Type
Active Comparator
Arm Description
Glipizide will be randomized to either 2.5mg or 5mg oral dose once daily for 5 days.
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin
Other Intervention Name(s)
SGLT2 inhibitor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Glipizide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of isoproterenol-stimulated lipolysis to measure metabolic flexibility in epicardial adipose tissue samples.
Description
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 Frame
Time to collect tissue collected during surgery (up to 15 minutes)
Secondary Outcome Measure Information:
Title
Average insulin mediated glucose uptake (IMGU) to measure insulin sensitivity in epicardial adipose tissue samples.
Description
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 Frame
Time to collect tissue collected during surgery (up to 15 minutes)
Title
Characterization of the inflammatory cytokine expression profile in epicardial adipose tissue samples.
Description
Analysis will be performed using Luminex to measure levels of inflammatory cytokines on the human adipocyte panel.
Time Frame
Time to collect tissue collected during surgery (up to 15 minutes)
Title
Distribution of adipose cell size in epicardial tissue.
Description
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 Frame
Time to collect tissue collected during surgery (up to 15 minutes)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tracey McLaughlin, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Ertugliflozin: Cardioprotective Effects on Epicardial Fat
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