Ketones, SGLT2, HFrEF

NCT06229678 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: STUDY00000012R01DK107680
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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

Heart Failure With Reduced Ejection Fraction; Type2diabetes

Keywords

ketones; cardiovascular benefit

Outcome Measures

Primary Outcomes (5)

• Change in Phosphocreatine

  A measure of phosphocreatine change from baseline to study end

  Baseline to 3 months

• Change in Adenosine Triphosphate (ATP)

  A measure of ATP change from baseline to study end

  Baseline to 3 months

• Change in Inorganic Phosphate

  A measure of inorganic phosphate change from baseline to study end

  Baseline to 3 months

• Change in Phosphodiester

  A measure of phosphodiester change from baseline to study end

  Baseline to 3 months

• ATPmax production

  Exercise induced ATPmax production change

  Baseline to 3 months

Secondary Outcomes (6)

• Plasma Beta-hydroxybutyrate (β-OH-B)

  baseline to 3 months

• Acetoacetate concentrations

  baseline to 3 months

• 6-min walking test

  baseline to 3 months

• Patient-Reported Outcomes Measure Information System

  baseline to 3 months

• plasma ketone concentration on myocardial function

  Baseline to 3months + 8 days

Study Arms (2)

Empagliflozin Group

EXPERIMENTAL

Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months

Drug: Empagliflozin 25 MG Oral Tablet; Drug: Acipimox 250 Mg Oral Capsule

Placebo group

PLACEBO COMPARATOR

Subjects will be randomized to receive the empagliflozin placebo for 3 months

Drug: Placebo; Drug: Acipimox 250 Mg Oral Capsule

Interventions

Empagliflozin 25 MG Oral Tablet DRUG

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

Also known as: jardiance

Empagliflozin Group

Placebo DRUG

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

Placebo group

Acipimox 250 Mg Oral Capsule DRUG

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

Empagliflozin Group; Placebo group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Texas Diabetes Institute - University Health System

San Antonio, Texas, 78207, United States

RECRUITING

MeSH Terms

Conditions

Ketosis

Interventions

empagliflozin; Tablets; acipimox

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Ralph DeFronzo, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ralph DeFronzo, MD

CONTACT

210-567-6691; defronzo@uthscsa.edu

Sivaram Neppala, MD

CONTACT

210-358-7200; neppalas@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants, and investigators will be blinded to the randomization
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized (2:1) placebo controlled double blind study

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 29, 2024
• Study Start: January 25, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (1)