This study will test whether pharmacologic agents that increase perfusion \[Potassium Nitrate (KNO3)\], with and without additional supplements that may improve mitochondrial function \[Propionyl-L-Carnitine (PLC) and Nicotinamide Riboside (NR)\], improve submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).
This study will test whether Potassium Nitrate (KNO3), with and without Propionyl-L-Carnitine (PLC) and Nicotinamide Riboside (NR), improves submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF). Additionally, the study will test whether the response to supplemental oxygen during a standardized MRI assessment of skeletal muscle oxidative capacity can identify HFpEF individuals who preferentially will benefit from either KNO3 alone or the combination of pharmacologic agents (KNO3 + PLC + NR)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
53
Potassium Nitrate is the active intervention that may increase blood flow to exercising muscle
Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside will be used as a combination intervention to both increase blood flow (KNO3) and mitochondrial function (PLC + NR)
Active control
University of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGSubmaximal Exercise Endurance
Time to exhaustion while exercising at 75% of peak workload
Time frame: week 6
Skeletal muscle oxidative capacity
MRI assessment of skeletal muscle oxidative phosphorylation capacity
Time frame: week 6
Vasodilatory Reserve
Percent change in systemic vascular resistance at baseline vs exhaustion
Time frame: week 6
Kansas City Cardiomyopathy Questionnaire Overall Summary Score
Assess the impact of our interventions on quality of life
Time frame: week 6
VO2 Kinetics
Assess the impact of our interventions on the kinetics of oxygen consumption (VO2 kinetics) during exercise and recovery "On" and "Off" kinetics will be modeled during the submaximal exercise transient
Time frame: week 6
Peak VO2
maximal rate of oxygen consumption determined during the last 30s of exercise.
Time frame: week 6
Steps per day
we will use actigraphy to document the average number of steps taken per day during the final week of each interventional period. Assess the impact of our interventions on ambulatory physical activity
Time frame: week 6
Skeletal muscle perfusion
MRI assessment of skeletal muscle oxidative phosphorylation capacity
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Time frame: week 6