Clincosm LogoSign in Get a demo

SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

Sponsor
The University of Texas Health Science Center at San Antonio (Other)
Overall Status
Recruiting
CT.gov ID
NCT05057806
Collaborator
Doris Duke Charitable Foundation (Other)
30
Enrollment
2
Locations
2
Arms
48.6
Anticipated Duration (Months)
15
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study team will examine the effects of SGLT2i (and SGLT2i-induced increases in plasma ketone concentrations) on skeletal muscle and cardiac ketone uptake, skeletal muscle bioenergetics, cardiopulmonary exercise capacity, and patient-reported functional outcomes.

Condition or Disease Intervention/Treatment Phase
  • Drug: Empagliflozin 25 MG
  • Drug: Placebo
 Early Phase 1

Detailed Description

The study team will examine effects of elevated plasma ketones caused by 12-week treatment with an SGLT2i (empagliflozin) treatment in participants with T2DM and HF. The study team will focus on three possible mechanisms of action for these effects and test the following:

(i) Skeletal muscle bioenergetics. Using 31P-MRS, the team will quantitate phosphocreatine [PCr], ATP, inorganic phosphate, phosphodiester, and intracellular pH. With 1H-MRS, and will measure intramyocellular lipid content at rest and ATPmax production after exercise. The team will examine the relationships between phosphorous metabolite concentrations, intramyocellular lipid content, and ATP generation before and after 12 weeks of SGLT2 inhibition.

(ii) Cardiopulmonary functional capacity.

(iii) Improvements in Patient-Reported Outcomes (PRO). The Patient-Reported Outcomes Measure Information System (PROMIS) Item Bank v2.0 - Physical Function - Short Form 20a will be used to evaluate self-reported physical function and well-being. This tool is a well-developed and validated method to obtain patient self-reported parameters of health in adults.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A randomized (2:1) placebo controlled double blind studyA randomized (2:1) placebo controlled double blind study
Masking:
Double (Participant, Investigator)
Masking Description:
Participants and investigators will be blinded to the randomization.
Primary Purpose:
Basic Science
Official Title:
Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors, Ketones, and Cardiovascular Benefit Research Plan
Actual Study Start Date :
Jan 13, 2021
Anticipated Primary Completion Date :
Oct 1, 2024
Anticipated Study Completion Date :
Feb 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Empagliflozin Group

Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months

Drug: Empagliflozin 25 MG
Empagliflozin 25MG will be administered orally once per day for 3 months
Other Names:
  • Jardiance

    		•
    Placebo Comparator: Placebo group

    Subjects will be randomized to receive the empagliflozin placebo for 3 months

    Drug: Placebo
    The placebo will be administered orally once per day for 3 months
    Other Names:
  • Placebo for Empagliflozin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Phosphocreatine [Baseline to 3 months]

      A measure of phosphocreatine change from baseline to study end

    2. Change in Adenosine Triphosphate (ATP) [Baseline to 3 months]

      A measure of ATP change from baseline to study end

    3. Change in Inorganic Phosphate [Baseline to 3 months]

      A measure of inorganic phosphate change from baseline to study end

    4. Change in Phosphodiester [Baseline to 3 months]

      A measure of phosphodiester change from baseline to study end

    5. ATPmax production [Baseline to 3 months]

      Exercise induced ATPmax production change

    Secondary Outcome Measures

    1. Plasma Beta-hydroxybutyrate (β-OH-B) [Baseline to 3 months]

      Change in β-OH-B

    2. Acetoacetate concentrations [Baseline to 3 months]

      Change in acetoacetate concentrations

    3. Cardiopulmonary Function [Baseline to 3 months]

      Change in cardiopulmonary functional capacity using oxygen uptake (VO2)

    4. 6 minute walk test [Baseline to 3 months]

      Change in the distance that can be covered in a 6 minute walk test

    5. Patient-Reported Outcomes Measure Information System (PROMIS) [Baseline to 3 months]

      Change in Physical function will be assessed by the PROMIS Item band v2.0 -Physical Function -Short Form 20a to evaluate patient-reported outcomes of physical function and well being.

    Eligibility Criteria

    Criteria

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

    • Type 2 Diabetes Mellitus

    • Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (EF) <50%

    • Age 18-80 years

    • BMI 23-38 kg/m2

    • Glycated hemoglobin (HbA1c) 5.5-10%

    • Blood Pressure (BP) ≤ 145/85 mmHg

    • Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2

    • Stable dose of guideline-directed medications for heart failure

    • Stable body weight (±4 pounds) over the last 3 months

    Exclusion Criteria:

    • Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone

    • Resting heart rate >120 bpm

    • Systolic BP>180mmHg and/or diastolic BP >100mmHg

    • Resting percentage of blood oxygen saturation (SpO2) < 85%

    • Physical disability preventing safe performance of the exercise protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Texas Diabetes Institute - University Health System San Antonio Texas United States 78207
    2 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229

    Sponsors and Collaborators

    • The University of Texas Health Science Center at San Antonio
    • Doris Duke Charitable Foundation

    Investigators

    • Principal Investigator: Carolina Solis-Herrera, MD, University of Texas Health Science Center San Antonio

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT05057806
    Other Study ID Numbers:
    • HSC20210528H
    First Posted:
    Sep 27, 2021
    Last Update Posted:
    Jan 19, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by The University of Texas Health Science Center at San Antonio
    Ketones
    Cardiovascular benefit
    Additional relevant MeSH terms:
    Heart Failure
    Empagliflozin

    Study Results

    No Results Posted as of Jan 19, 2022