The Effect of Nicotinamide Riboside on Skeletal Muscle Function in Heart Failure Subjects
Heart Failure
About this trial
This is an interventional basic science trial for Heart Failure focused on measuring Mitochondrial bioenergetic dysfunction, Mitochondrial oxidative phosphorylation in skeletal muscles, Hyperacetylation of mitochondrial bioenergetic enzymes, NAD+ dependent sirtuin enzymes, NAD+/NADH ratio
Eligibility Criteria
- INCLUSION CRITERIA:
Men and women between the ages of 18 and 75 years with New York Heart Association (NYHA) Functional Classification Class II-III systolic heart failure ( Left Ventricular Ejection Fraction (LVEF) by standard echocardiography or radionuclide ventriculography of less than or equal to 45%) deemed to be non-ischemic or ischemic in origin.
Clinically stable (no cardiac procedures or hospitalizations for hospitalizations for cardiac causes, including HF, ischemia or arrhythmia) within the previous 3 months
Ability to undergo study procedures, including scheduled visits, blood draws, skeletal muscle exercise NMR spectroscopy and CPET testing
Willingness/ability to provide informed consent
Must be DEERS eligible to be enrolled in a research protocol at Walter Reed National Military Medical Center (WRNMMC).
EXCLUSION CRITERIA:
Heart failure with preserved ejection fraction (LVEF greater than 45%)
Change in heart failure medications due to deterioration of function with the exception of up- or down-titration of diuretic dose up to 100% of baseline dose.
Heart failure due to etiologies other than non-ischemic or ischemic. Examples of exclusionary heart failure etiologies include primary valvular disease, or infiltrative or inflammatory cardiomyopathies.
Cardiac surgery, percutaneous coronary intervention (PCI) or cardiac device implantation within the previous 3 months
Hospitalizations for cardiovascular causes, including heart failure, chest pain, stroke/TIA or arrhythmias within the previous 3 months
Inability to perform Study visits or procedures (e.g., physical inability to perform exercise testing)
Unwillingness/inability to provide informed consent
ALT greater than x3 upper limit of normal, hepatic insufficiency or active liver disease
Recent history of acute gout
Chronic renal insufficiency with creatinine greater than 2.5mg/dl
Pregnant (or likely to become pregnant) women
Significant co-morbidity likely to cause death in the 6 month follow-up period
Significant active history of substance abuse within the previous 5 years
Current participation in another drug study
History of intolerance to NR precursor compounds, including niacin or nicotinamide
MRI incompatible hardware including pacemakers or ICD s
Study adherence concerns
Individuals with diabetes type 1 and 2 who use insulin
Women of child-bearing potential unwilling to use contraception or unwilling to practice abstinence
Breastfeeding women unwilling to stop breastfeeding
Sites / Locations
- Walter Reed National Military Medical Center
- National Institutes of Health Clinical Center
Arms of the Study
Arm 1
Experimental
Nicotinamide Riboside in patients with stable heart failure
Nicotinamide Riboside (NR) will be started at 500 mg daily (250 mg BID) then increased at two weekly intervals by 250 mg/dose (BID) (500 mg/day) to a final dose of 1000 mg PO BID (2000 mg/day) in patients with stable, systolic heart failure.