SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

NCT05057806 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: HSC20210528H2021176
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Type2 Diabetes; Heart Failure With Preserved Ejection Fraction

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 (5)

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

  Baseline to 3 months

• Acetoacetate concentrations

  Baseline to 3 months

• Cardiopulmonary Function

  Baseline to 3 months

• 6 minute walk test

  Baseline to 3 months

• Patient-Reported Outcomes Measure Information System (PROMIS)

  Baseline to 3 months

Study Arms (2)

Empagliflozin Group

EXPERIMENTAL

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

Drug: Empagliflozin 25 MG

Placebo group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Empagliflozin 25 MG 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

Also known as: Placebo for Empagliflozin

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 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 23-38 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Doris Duke Charitable Foundation: collaborator
• Max and Minnie Tomerlin Voelcker Fund: collaborator

Study Sites (2)

Texas Diabetes Institute - University Health System

San Antonio, Texas, 78207, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Ketosis

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

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

Study Officials

• Carolina Solis-Herrera, MD

  University of Texas Health Science Center San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carolina Solis-Herrera, MD

CONTACT

210-567-4900; solisherrera@uthscsa.edu

Yuejuan Qin, PhD

CONTACT

210-358-7200; qiny@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: September 15, 2021
• First Posted: September 27, 2021
• Study Start: January 13, 2021
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

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

Locations

US (2)