Ertugliflozin: Cardioprotective Effects on Epicardial Fat
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Ertugliflozin
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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:
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Active Comparator: Glipizide
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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.
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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patient at Stanford Cardiovascular Surgery clinic who is scheduled for cardiac bypass surgery
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history of Diabetes Mellitus Type 2 currently taking metformin or diet-controlled
Exclusion Criteria:
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allergy or intolerance to interventional medication
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currently taking any anti-diabetic medication other than metformin
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Stanford University | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Tracey McLaughlin, MD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 52647