SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan
Purpose
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.
Conditions
- Type2 Diabetes
- Heart Failure With Preserved Ejection Fraction
Eligibility
- Eligible Ages
- Between 18 Years and 80 Years
- Eligible Genders
- 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.
Study Design
- Phase
- Early Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- A randomized (2:1) placebo controlled double blind study
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
- Masking Description
- Participants and investigators will be blinded to the randomization.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Empagliflozin Group |
Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months |
|
|
Placebo Comparator Placebo group |
Subjects will be randomized to receive the empagliflozin placebo for 3 months |
|
Recruiting Locations
San Antonio, Texas 78207
San Antonio, Texas 78229
More Details
- Status
- Recruiting
- Sponsor
- The University of Texas Health Science Center at San Antonio
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.