Recruiting
Early Phase 1

SGLT2 Inhibitor

Sponsor:

The University of Texas Health Science Center at San Antonio

Code:

NCT06229678

Conditions

Type2diabetes

Heart Failure With Reduced Ejection Fraction

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Empagliflozin 25 MG Oral Tablet

Placebo

Acipimox 250 Mg Oral Capsule

Study Details

Brief 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

Conditions

Type2diabetes

Heart Failure With Reduced Ejection Fraction

Study ID

NCT06229678

Start date

Jan 25, 2024

Status verified date

Feb, 2026

Completion date

Mar 1, 2027

Anticipated

Primary completion date

Nov 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

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 23-44 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 Criteria:

  • 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.

Study Design

Enrollment

71 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

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

Interventions

Empagliflozin 25 MG Oral Tablet

Empagliflozin 25MG will be administered orally once per day for 3 months

Placebo

The placebo will be administered orally once per day for 3 months

Acipimox 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

Primary outcome measure

  • Change in Phosphocreatine [ Time Frame: Baseline to 3 months ]
  • Change in Adenosine Triphosphate (ATP) [ Time Frame: Baseline to 3 months ]
  • Change in Inorganic Phosphate [ Time Frame: Baseline to 3 months ]
  • Change in Phosphodiester [ Time Frame: Baseline to 3 months ]
  • ATPmax production [ Time Frame: Baseline to 3 months ]

Central Contacts and Locations

Central contacts

Ralph DeFronzo, MD

210-567-6691defronzo@uthscsa.edu

Sivaram Neppala, MD

210-358-7200neppalas@uthscsa.edu

Locations

Texas Diabetes Institute - University Health System

Recruiting

San Antonio, Texas, United States, 78207

Contacts

Sivaram Neppala, MD

210-358-7200neppalas@uthscsa.edu

Jemema Rajan, MD

210-358-7200rajanj@uthscsa.edu

Principal Investigator:

Ralph DeFronzo, MD

More Information

Sponsor

The University of Texas Health Science Center at San Antonio

Last update posted

Feb 5, 2026

Last verified

Feb, 2026

Keywords

  • ketones
  • cardiovascular benefit

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by The University of Texas Health Science Center at San Antonio on 2026-02-05.