Ertugliflozin: Cardioprotective Effects on Epicardial Fat

Sponsor
Stanford University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04167761
Collaborator
Merck Sharp & Dohme LLC (Industry)
36
1
2
25
1.4

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
Early Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
unblinded randomized trialunblinded randomized trial
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Ertugliflozin: Cardioprotective Effects on Epicardial Fat
Actual Study Start Date :
Jul 1, 2020
Anticipated Primary Completion Date :
Jul 31, 2022
Anticipated Study Completion Date :
Jul 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ertugliflozin

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

    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.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    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.
    Responsible Party:
    Tracey McLaughlin, Professor of Medicine, Stanford University
    ClinicalTrials.gov Identifier:
    NCT04167761
    Other Study ID Numbers:
    • 52647
    First Posted:
    Nov 19, 2019
    Last Update Posted:
    Dec 23, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Tracey McLaughlin, Professor of Medicine, Stanford University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 23, 2021