RecruitingEarly Phase 1NCT06229678

Ketones, SGLT2, HFrEF

Ketones, Muscle Metabolism, and SGLT2 Inhibitors

Sponsor

The University of Texas Health Science Center at San Antonio

Enrollment

71 participants

Start Date

Jan 25, 2024

Study Type

INTERVENTIONAL

Conditions

Heart Failure With Reduced Ejection Fraction Type2diabetes

Summary

The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria10

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 23-44 kg/m2
Glycated hemoglobin (HbA1c) 6.0-10.0%
Blood Pressure (BP) ≤ 145/85 mmHg
Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2
Only Type 2 diabetics treated with diet/exercise, metformin, sulfonylureas, metformin/sulfonylurea, Glucagon-like peptide-1 receptor agonist (GLP-1 RA), or insulin
Stable body weight (±4 pounds) over the previous 3 months prior to enrollment
Ability to understand study procedures and to comply with them for the entire length of the study.

Exclusion Criteria8

Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular heart disease, hypertrophic obstructive cardiomyopathy.
Significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose or addition of another heart failure medication)
Type 2 Diabetics treated with Dipeptidyl Peptidase-4 Inhibitor (DPP4i) or pioglitazone
Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will be performed before each MRI study to assess current status. For women of child-bearing age (WOCBA) willingness to use contraception, if applicable.
Allergy/sensitivity to study drugs or their ingredients.
Cancer.
Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

Interventions

DRUGEmpagliflozin 25 MG Oral Tablet

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

DRUGAcipimox 250 Mg Oral Capsule

subjects will be started on acipimox 250mg every 6 hours for 8 days while on continued empagliflozin/placebo therapy. This will be added at the end of 3 months after they finished baseline studies