NAD+ and Exercise in FA

Korábbi kezelés

• Concurrent use of any medications, including statins, likely to increase risk of NR toxicity.
• Use of supraphysiologic steroids.
• Use of any investigational agent within 4 weeks of enrollment, except open-label extension phase.

Más betegség

• HgbA1c \> 8.5% and/or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue.
• Uncontrolled and persistent arrhythmias that are felt to be clinically significant.
• Any contraindication to MRI. Including:
  • Any intra-luminal implant, filter, stent or valve replacement
  • Any type of life assist device, pump, or prosthetic
  • Any vascular clip or clamp
  • Any surgically placed clips or clamps or bands on visceral organs
  • Any intracranial implants of any type other than dental fillings
  • Any non-removable piercings, jewelry, or medicinal patch
  • Any personal history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic examination.
  • Any personal history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation.
  • Inability to lie flat in the MRI scanner for 60-90 minutes.
  • participants who cannot complete the MRI will not be excluded from participation in the remainder of the study procedures if they meet those inclusion and exclusion criteria
• Any medical condition, in the opinion of the investigator that will interfere with the safe completion of the study.

Laborértékek

• Laboratory abnormalities that indicate clinically significant anemia or bleeding risk. (Hemoglobin \< 10 g/dL or Platelets \< 100K)
• Laboratory abnormalities that indicate clinically significant kidney disease using serum creatinine and Modification of Diet in Renal Disease (MDRD) equation. (Estimated Glomerular Filtration Rate (eGFR) \< 60 ml/min/1.73 m2)
• Laboratory abnormalities that indicate clinically significant liver disease. (Aspartate Aminotransferase (AST)/Serum Glutamic Oxaloacetic Transaminase (SGOT) 3.0 x Upper Limit of Normal and/or Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) 3.0 x Upper Limit of Normal)
• Known history of moderate or severe left ventricular systolic dysfunction (Left Ventricular Ejection Fraction (LVEF) \< 45%)

Egyéb

• Known sensitivity to NR.
• Standard contraindications to exercise testing.
• Inability to sit and pedal unassisted in a cycle ergometry chair, at a cadence of at least 55 rotations per minute (rpm) during unloaded warm up, in a cycle ergometry chair and complete a maximal Cardio Pulmonary Exercise Test (CPET)
• Inability to sit and pedal unassisted in a recumbent tricycle.
• Females: pregnant, lactating, or planning to become pregnant during their participation.
• Parents/guardians or participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

• Molecular diagnosis of Friedrich's Ataxia (FA).
• Males and Females, Age 10 to 40 years (inclusive).
• Girls, 11 years of age and older, must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
• Not currently meeting exercise guidelines as outlined by The Physical Activity Guidelines for Americans.
  • Children and Adolescents should do 60 minutes (1 hour) or more of moderate-to-vigorous physical activity daily.
  • As a part of their physical activity, children and adolescents should include muscle-strengthening physical activity on at least 3 days a week.
  • Adults should do at least 150 minutes (2 hours and 30 minutes) to 300 minutes (5 hours) a week of moderate-intensity, or 75 minutes (1 hour and 15 minutes) to 150 minutes (2 hours and 30 minutes) a week of vigorous-intensity aerobic physical activity.
  • Adults should also do muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on 2 or more days a week.
• Cardiac echocardiogram or cardiac MRI, performed within 1 year of enrollment, showing an LVEF \> 45%
• ECG, performed within 1 year of enrollment, without clinically significant arrhythmia.
• Weight \> 24 kg
• Parental/guardian permission (informed consent) and if appropriate, child assent.