SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan
- Conditions
- Type2 DiabetesHeart Failure With Preserved Ejection Fraction
- Interventions
- Drug: Placebo
- Registration Number
- NCT05057806
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo group Placebo Subjects will be randomized to receive the empagliflozin placebo for 3 months Empagliflozin Group Empagliflozin 25 MG Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months
- Primary Outcome Measures
Name Time Method Change in Phosphocreatine Baseline to 3 months A measure of phosphocreatine change from baseline to study end
ATPmax production Baseline to 3 months Exercise induced ATPmax production change
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
- Secondary Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (2)
Texas Diabetes Institute - University Health System
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States