SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

NCT ID: NCT05057806

Last Updated: 2025-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-13

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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The study team will examine 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 quantitate 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) Cardiopulmonary functional capacity.

(iii) Improvements in Patient-Reported Outcomes (PRO). The Patient-Reported Outcomes Measure Information System (PROMIS) Item Bank v2.0 - Physical Function - Short Form 20a 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.

Conditions

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Type2 Diabetes Heart Failure With Preserved Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A randomized (2:1) placebo controlled double blind study
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators
Participants and investigators will be blinded to the randomization.

Study Groups

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Empagliflozin Group

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

Group Type EXPERIMENTAL

Empagliflozin 25 MG

Intervention Type DRUG

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

Placebo group

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Empagliflozin 25 MG

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Jardiance Placebo for Empagliflozin

Eligibility Criteria

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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 23-38 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Doris Duke Charitable Foundation

OTHER

Sponsor Role collaborator

Max and Minnie Tomerlin Voelcker Fund

UNKNOWN

Sponsor Role collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carolina Solis-Herrera, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health Science Center San Antonio

Locations

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Texas Diabetes Institute - University Health System

San Antonio, Texas, United States

Site Status RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Carolina Solis-Herrera, MD

Role: CONTACT

210-567-4900

Yuejuan Qin, PhD

Role: CONTACT

210-358-7200

Facility Contacts

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Yuejuan Qin, PhD

Role: primary

210-358-7200

Sivaram Neppala, MD

Role: backup

210-358-7200

Carolina Solis-Herrera, MD

Role: primary

210-567-4800

Yuejuan Qin, PhD

Role: backup

210-358-7200

Other Identifiers

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2021176

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HSC20210528H

Identifier Type: -

Identifier Source: org_study_id

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