NAD+ and Exercise in FA (ExRx in FA)
Friedreich Ataxia 1
About this trial
This is an interventional other trial for Friedreich Ataxia 1
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Known sensitivity to NR.
- Concurrent use of any medications, including statins, likely to increase risk of NR toxicity.
- HgbA1c > 8.5% and/or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue.
- Use of supraphysiologic steroids.
- 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)
- Uncontrolled and persistent arrhythmias that are felt to be clinically significant.
- Known history of moderate or severe left ventricular systolic dysfunction (Left Ventricular Ejection Fraction (LVEF) < 45%)
- 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.
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
- Use of any investigational agent within 4 weeks of enrollment, except open-label extension phase.
- Females: pregnant, lactating, or planning to become pregnant during their participation.
- Any medical condition, in the opinion of the investigator that will interfere with the safe completion of the study.
- Parents/guardians or participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Sites / Locations
- Children's Hospital of PhiladelphiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Placebo Comparator
Experimental
Experimental
Nicotinamide Riboside (NR)
Placebo
Exercise Intervention and NR
Exercise Intervention and Placebo
Investigators will use Good Manufacturing Process (GMP)-grade 300 mg capsules of the dietary supplement nicotinamide riboside (ChromaDex, Irvine CA). Investigators dose based on body weight, and monitor for adverse effects (AEs). For individuals with weight > 72 kg: 900 mg po qd x 12 wks. For individuals with weight > 48 kg and ≤ 72 kg: 600 mg po qd x 12 wks. For individuals with weight 24 ≤ 48 kg: 300 mg po qd x 12 wks.
Matched placebo will contain the same excipients without the active supplement and is generally recognized as safe. The placebo will be covered in an identical capsule (NR will be covered in the same capsule). Doses of placebo will match the body weight schema for dosing of NR. Investigators dose based on body weight, and monitor for adverse effects (AEs). For individuals with weight > 72 kg: 900 mg po qd x 12 wks. For individuals with weight > 48 kg and ≤ 72 kg: 600 mg po qd x 12 wks. For individuals with weight 24 ≤ 48 kg: 300 mg po qd x 12 wks.
The exercise program consists of at-home training sessions: 3 aerobic sessions per week on the in-home bike trainer, and 2 resistance exercise sessions per week using resistance bands. All sessions will begin with stretching and brief aerobic warm-up exercise on the in-home bike trainer. On resistance training days, subjects will be given instructions to complete circuits of resistance exercises. Participants in this arm will receive both the Exercise Intervention and the NR.
The exercise program consists of at-home training sessions: 3 aerobic sessions per week on the in-home bike trainer, and 2 resistance exercise sessions per week using resistance bands. All sessions will begin with stretching and brief aerobic warm-up exercise on the in-home bike trainer. On resistance training days, subjects will be given instructions to complete circuits of resistance exercises. Participants in this arm will receive both the Exercise Intervention and the Placebo.