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SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

Primary Purpose

Type2 Diabetes, Heart Failure With Preserved Ejection Fraction

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Empagliflozin 25 MG

Placebo

About this trial

This is an interventional basic science trial for Type2 Diabetes focused on measuring Ketones, Cardiovascular benefit

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
Stable body weight (±4 pounds) over the last 3 months

Exclusion Criteria:

Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone
Resting heart rate >120 bpm
Systolic BP>180mmHg and/or diastolic BP >100mmHg
Resting percentage of blood oxygen saturation (SpO2) < 85%
Physical disability preventing safe performance of the exercise protocol.

Sites / Locations

Texas Diabetes Institute - University Health SystemRecruiting
University of Texas Health Science Center at San AntonioRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Empagliflozin Group

Placebo group

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in Phosphocreatine

A measure of phosphocreatine change from baseline to study end

Change in Adenosine Triphosphate (ATP)

A measure of ATP change from baseline to study end

Change in Inorganic Phosphate

A measure of inorganic phosphate change from baseline to study end

Change in Phosphodiester

A measure of phosphodiester change from baseline to study end

ATPmax production

Exercise induced ATPmax production change

Secondary Outcome Measures

Plasma Beta-hydroxybutyrate (β-OH-B)

Change in β-OH-B

Acetoacetate concentrations

Change in acetoacetate concentrations

Cardiopulmonary Function

Change in cardiopulmonary functional capacity using oxygen uptake (VO2)

6 minute walk test

Change in the distance that can be covered in a 6 minute walk test

Patient-Reported Outcomes Measure Information System (PROMIS)

Change in Physical function will be assessed by the PROMIS Item band v2.0 -Physical Function -Short Form 20a to evaluate patient-reported outcomes of physical function and well being.

Full Information

NCT ID

NCT05057806

First Posted

September 15, 2021

Last Updated

August 29, 2023

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

Doris Duke Charitable Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT05057806

Brief Title

SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

Official Title

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 13, 2021 (Actual)

Primary Completion Date

November 30, 2026 (Anticipated)

Study Completion Date

March 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

Doris Duke Charitable Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type2 Diabetes, Heart Failure With Preserved Ejection Fraction

Keywords

Ketones, Cardiovascular benefit

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

ParticipantInvestigator

Masking Description

Participants and investigators will be blinded to the randomization.

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Empagliflozin Group

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Empagliflozin 25 MG

Other Intervention Name(s)

Jardiance

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo for Empagliflozin

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Phosphocreatine

Description

A measure of phosphocreatine change from baseline to study end

Time Frame

Baseline to 3 months

Title

Change in Adenosine Triphosphate (ATP)

Description

A measure of ATP change from baseline to study end

Time Frame

Baseline to 3 months

Title

Change in Inorganic Phosphate

Description

A measure of inorganic phosphate change from baseline to study end

Time Frame

Baseline to 3 months

Title

Change in Phosphodiester

Description

A measure of phosphodiester change from baseline to study end

Time Frame

Baseline to 3 months

Title

ATPmax production

Description

Exercise induced ATPmax production change

Time Frame

Baseline to 3 months

Secondary Outcome Measure Information:

Title

Plasma Beta-hydroxybutyrate (β-OH-B)

Description

Change in β-OH-B

Time Frame

Baseline to 3 months

Title

Acetoacetate concentrations

Description

Change in acetoacetate concentrations

Time Frame

Baseline to 3 months

Title

Cardiopulmonary Function

Description

Change in cardiopulmonary functional capacity using oxygen uptake (VO2)

Time Frame

Baseline to 3 months

Title

6 minute walk test

Description

Change in the distance that can be covered in a 6 minute walk test

Time Frame

Baseline to 3 months

Title

Patient-Reported Outcomes Measure Information System (PROMIS)

Description

Change in Physical function will be assessed by the PROMIS Item band v2.0 -Physical Function -Short Form 20a to evaluate patient-reported outcomes of physical function and well being.

Time Frame

Baseline to 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 Stable body weight (±4 pounds) over the last 3 months Exclusion Criteria: Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone Resting heart rate >120 bpm Systolic BP>180mmHg and/or diastolic BP >100mmHg Resting percentage of blood oxygen saturation (SpO2) < 85% Physical disability preventing safe performance of the exercise protocol.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Carolina Solis-Herrera, MD

Phone

210-567-4900

solisherrera@uthscsa.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Yuejuan Qin, PhD

Phone

210-358-7200

qiny@uthscsa.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carolina Solis-Herrera, MD

Organizational Affiliation

University of Texas Health Science Center San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

Texas Diabetes Institute - University Health System

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78207

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yuejuan Qin, PhD

Phone

210-358-7200

Qiny@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Sivaram Neppala, MD

Phone

210-358-7200

neppalas@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Ralph DeFronzo, MD

First Name & Middle Initial & Last Name & Degree

Carolina Solis-Herrera, MD

Facility Name

University of Texas Health Science Center at San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Carolina Solis-Herrera, MD

Phone

210-567-4800

solisherrera@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Yuejuan Qin, PhD

Phone

210-358-7200

qiny@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Ralph DeFronzo, MD

First Name & Middle Initial & Last Name & Degree

Carolina Solis-Herrera, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The PI will actively participate in journal clubs and symposia and present abstracts at national meetings, as well as submitting manuscripts to top peer-reviewed journals.

Learn more about this trial

SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

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