Heart Failure With Preserved Ejection Fraction, Type2 Diabetes
Conditions
Keywords
Ketones, Cardiovascular benefit
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.
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.
Interventions
DRUGEmpagliflozin 25 MG
Empagliflozin 25MG will be administered orally once per day for 3 months
DRUGPlacebo
The placebo will be administered orally once per day for 3 months
Sponsors
The University of Texas Health Science Center at San Antonio
Doris Duke Charitable Foundation
Max and Minnie Tomerlin Voelcker Fund
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigators will be blinded to the randomization.
Intervention model description
A randomized (2:1) placebo controlled double blind study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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 and Diabetes * Stable body weight (±4 pounds) over the last 3 months * Does not suffer from severe claustrophobia * No contraindication for MRI (metal plates, screws, shrapnel, pins, or cardiac pacemaker)
Exclusion criteria
* Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone * Pregnancy, lactation or plans to become pregnant * Allergy/sensitivity to study drugs or their ingredients * Cancer * Current drug or alcohol use or dependence * Inability or unwillingness of individual or legal guardian/representative to give written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Phosphocreatine | Baseline to 3 months | A measure of phosphocreatine change from baseline to study end |
| Change in Adenosine Triphosphate (ATP) | Baseline to 3 months | A measure of ATP change from baseline to study end |
| Change in Inorganic Phosphate | Baseline to 3 months | A measure of inorganic phosphate change from baseline to study end |
| Change in Phosphodiester | Baseline to 3 months | A measure of phosphodiester change from baseline to study end |
| ATPmax production | Baseline to 3 months | Exercise induced ATPmax production change |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Beta-hydroxybutyrate (β-OH-B) | Baseline to 3 months | Change in β-OH-B |
| Acetoacetate concentrations | Baseline to 3 months | Change in acetoacetate concentrations |
| Cardiopulmonary Function | Baseline to 3 months | Change in cardiopulmonary functional capacity using oxygen uptake (VO2) |
| 6 minute walk test | Baseline to 3 months | Change in the distance that can be covered in a 6 minute walk test |
| 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. |
Countries
United States
Contacts
CONTACTCarolina Solis-Herrera, MD
CONTACTFrancisca M Acosta, PhD
PRINCIPAL_INVESTIGATORCarolina Solis-Herrera, MD
The University of Texas Health Science Center at San Antonio
Outcome results
None listed