SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research Plan

Type2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05057806
• Other study ID #: HSC20210528H
• Secondary ID: 2021176
• Status: Recruiting
• Phase: Early Phase 1
• Start date: January 13, 2021
• Est. completion date: March 31, 2027

Study information

• Verified date: January 2024
• Source: The University of Texas Health Science Center at San Antonio
• Contact: Carolina Solis-Herrera, MD
• Phone: 210-567-4900
• Email: solisherrera[@]uthscsa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 31, 2027
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Type2 Diabetes

Intervention

Drug:
• Empagliflozin 25 MG
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

Locations

Country	Name	City	State
United States	Texas Diabetes Institute - University Health System	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	Doris Duke Charitable Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Phosphocreatine	A measure of phosphocreatine change from baseline to study end	Baseline to 3 months
Primary	Change in Adenosine Triphosphate (ATP)	A measure of ATP change from baseline to study end	Baseline to 3 months
Primary	Change in Inorganic Phosphate	A measure of inorganic phosphate change from baseline to study end	Baseline to 3 months
Primary	Change in Phosphodiester	A measure of phosphodiester change from baseline to study end	Baseline to 3 months
Primary	ATPmax production	Exercise induced ATPmax production change	Baseline to 3 months
Secondary	Plasma Beta-hydroxybutyrate (ß-OH-B)	Change in ß-OH-B	Baseline to 3 months
Secondary	Acetoacetate concentrations	Change in acetoacetate concentrations	Baseline to 3 months
Secondary	Cardiopulmonary Function	Change in cardiopulmonary functional capacity using oxygen uptake (VO2)	Baseline to 3 months
Secondary	6 minute walk test	Change in the distance that can be covered in a 6 minute walk test	Baseline to 3 months
Secondary	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.	Baseline to 3 months