The Effect of Nicotinamide Riboside on Skeletal Muscle Function in Heart Failure Subjects
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Nicotinamide Riboside
Intervention description: Nicotinamide Riboside (NR) will be started at 500 mg daily (250 mg BID) be increased at two weekly intervals by 250 mg/dose (BID) (500 mg/day) to a final dose of 1000mg PO BID (2000 mg/day).
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Mitochondrial bioenergetic dysfunction; Mitochondrial oxidative phosphorylation in skeletal muscles; Hyperacetylation of mitochondrial bioenergetic enzymes; NAD+ dependent sirtuin enzymes; NAD+/NADH ratio

Summary:

      Background:

      People are living longer and are more likely to survive a heart attack if they have one.
      Longer life expectancy is good but it also means more people get chronic heart failure over
      time. This is a condition in which the heart doesn't pump blood as well as it should.
      Treatment of chronic heart failure has not improved much in a few decades. Researchers want
      to see if giving a dietary supplement to people with heart failure can help their heart
      function. The supplement is nicotinamide riboside (NR).

      Objective:

      To study how NR affects skeletal muscle function in people with heart failure.

      Eligibility:

      Adults ages 18-70 with clinically stable systolic heart failure

      Design:

      Participants will be screened with a medical history and physical exam. They will answer
      demographic questions and review their current medical treatments. They will have blood and
      urine tests. They will have an echocardiogram. This uses sound waves to test heart function.

      Participants will have 8 study visits over 16 weeks. At these visits, they will have some of
      the following:

      Repeat of screening tests

      Skin sample taken

      Skeletal muscle exercise Nuclear magnetic resonance (NMR) spectroscopy. Muscles will be
      measured while participants do foot exercises.

      Cardiopulmonary exercise testing. Participants may ride a stationary bike or walk on a
      treadmill. A facemask will analyze their breath. Heart and blood pressure measurements will
      be taken.

      Participants will take the supplement in pill form each day for 12 weeks. Pill bottles will
      be checked at study visits.

      Participants should not significantly change their activity levels during the study.
    

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