Ketones, SGLT2, HFrEF

Last updated: May 16, 2025
Sponsor: The University of Texas Health Science Center at San Antonio
Overall Status: Suspended

Phase

1

Condition

Congestive Heart Failure

Chest Pain

Hyponatremia

Treatment

Placebo

Empagliflozin 25 MG Oral Tablet

Acipimox 250 Mg Oral Capsule

Clinical Study ID

NCT06229678
STUDY00000012
R01DK107680
  • Ages 18-70
  • All Genders

Study 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 Criteria

Inclusion

Inclusion Criteria:

  • Type 2 Diabetes Mellitus

  • Class II-III New York Heart Association (NYHA) heart failure and reduced ejectionfraction (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), orinsulin

  • 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 lengthof the study.

Exclusion

Exclusion Criteria:

  • Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictivepericarditis, severe valvular heart disease, hypertrophic obstructivecardiomyopathy.

  • Significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose or addition of another heart failuremedication)

  • Type 2 Diabetics treated with Dipeptidyl Peptidase-4 Inhibitor (DPP4i) orpioglitazone

  • Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will beperformed before each MRI study to assess current status. For women of child-bearingage (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 siteinvestigator, would interfere with adherence to study requirements.

  • Inability or unwillingness of individual or legal guardian/representative to givewritten informed consent.

Study Design

Total Participants: 71
Treatment Group(s): 3
Primary Treatment: Placebo
Phase: 1
Study Start date:
January 25, 2024
Estimated Completion Date:
March 01, 2027

Study Description

The study team will examine the 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 quantify 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) LV systolic and diastolic function using cardiac MRI in type 2 diabetic patients with Class II-III NYHA heart failure and reduced EF.

(iii) To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function and myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.

(iv) Improvements in Patient-Reported Outcomes (PRO). Kansas City Cardiomyopathy Questionnaire ( KCCQ) scoring 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.

Connect with a study center

  • Texas Diabetes Institute - University Health System

    San Antonio, Texas 78207
    United States

    Site Not Available

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