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
The study team will examine the 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 quantify 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) LV systolic and diastolic function using cardiac MRI in type 2 diabetic patients with Class II-III NYHA heart failure and reduced EF. (iii) To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function and myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin. (iv) Improvements in Patient-Reported Outcomes (PRO). Kansas City Cardiomyopathy Questionnaire ( KCCQ) scoring 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
71
Empagliflozin 25MG will be administered orally once per day for 3 months
The placebo will be administered orally once per day for 3 months
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
Texas Diabetes Institute - University Health System
San Antonio, Texas, United States
RECRUITINGChange in Phosphocreatine
A measure of phosphocreatine change from baseline to study end
Time frame: Baseline to 3 months
Change in Adenosine Triphosphate (ATP)
A measure of ATP change from baseline to study end
Time frame: Baseline to 3 months
Change in Inorganic Phosphate
A measure of inorganic phosphate change from baseline to study end
Time frame: Baseline to 3 months
Change in Phosphodiester
A measure of phosphodiester change from baseline to study end
Time frame: Baseline to 3 months
ATPmax production
Exercise induced ATPmax production change
Time frame: Baseline to 3 months
Plasma Beta-hydroxybutyrate (β-OH-B)
Change in β-OH-B with medication
Time frame: baseline to 3 months
Acetoacetate concentrations
Change in acetoacetate concentrations
Time frame: baseline to 3 months
6-min walking test
Change in the distance that can be covered in a 6 minute walk test
Time frame: baseline to 3 months
Patient-Reported Outcomes Measure Information System
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
By checking KCCQ (Kansas City Cardiomyopathy) scoring: Responses are categorized under 3 sub scales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three sub scale scores.
Time frame: baseline to 3 months
plasma ketone concentration on myocardial function
To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.
Time frame: Baseline to 3months + 8 days
plasma ketone concentration on myocardial blood flow
To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.
Time frame: Baseline to 3months + 8 days