Study Overview:

Research clinicians at the Children’s Hospital of Philadelphia are enrolling participants in a study to evaluate the effects of a dietary supplement combined with exercise. This is a randomized, placebo-controlled trial. The primary outcome measure is changes in aerobic capacity, which is the body’s ability to take in, transport and use oxygen during exercise. This study will be enrolling over 4 years, starting in 2020, with a target enrolment of 72 participants. Compensation is provided for study time.

Anyone considering participating in a clinical trial should discuss the matter with their physician. FARA does not endorse or recommend any particular studies.

Study Details:

Friedreich’s Ataxia (FA) is a progressive neurodegenerative disease affecting 1 in 50,000 individuals in the U.S. Currently, there is no approved treatment.

There is a critical knowledge gap regarding the best ways to intervene to increase aerobic capacity (VO2max on exercise testing) in FA. Exercise is the most potent known stimulus for increasing muscle mass and mitochondrial oxidative phosphorylation (OXPHOS) capacity, increasing VO2max, and increasing insulin sensitivity (Si), however, it has not been studied in FA. One adaptation seen in exercised muscles is an increase in muscle nicotinamide adenine dinucleotide (NAD+), a cofactor required for glycolytic and mitochondrial adenosine triphosphate (ATP) production. In skeletal- and cardiac muscle-specific frataxin (FXN) knock-out animals, NAD+ precursors rescued cardiac function to near-normal, additionally highlighting its translational potential in FA. Nicotinamide riboside (NR) is a NAD+ precursor currently available as a dietary supplement (Tru Niagen ®, ChromaDex, Irvine CA) that is expected to be safe and well-tolerated in adults and children. The central hypothesis is that exercise + NR will increase skeletal muscle mitochondrial OXPHOS and increase muscle mass to increase VO2max in FA. The investigators expect that exercise + NR will also increase Si in this cohort.

Participation is this study involves completion of two (2) in-person clinic visits, each lasting 2 days, over a 12-week period. During the study period, you will be asked to complete blood testing, exercise testing, administration of a dietary supplement, MRI scans, oral glucose tolerance testing (with a non-FDA approved stable isotope product) and optional muscle biopsies.

Key Inclusion Criteria:

  • Genetically-confirmed diagnosis of FA
  • Age 10-40 years old
  • Able to complete exercise testing
  • Not currently meeting exercise guidelines as outlined by The Physical Activity Guidelines for Americans.
  • Specific cardiac disease requirements (LVEF >45%, absence of clinically significant arrhythmia)

Key Exclusion Criteria:

  • Known sensitivity to NR
  • Use of medications known to increase NR toxicity (e.g., statins)
  • HgbA1c > 8.5% and/or diabetes mellitus requiring insulin or insulin secretagogue
  • Contraindication to MRI
  • Laboratory abnormalities indicative of significant kidney or liver disease
  • 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.
  • Use of an investigational drug within 4 weeks of enrollment, except open label extension phase

Additional inclusion and exclusion criteria may apply and will be evaluated by a study doctor.

Length of Study Commitment:

  • Twelve weeks

Participating Study Locations

Institution Name and LocationStudy Coordinator Contact InformationStatus

Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania

Kristin L. Wade, MLitt


Explore the FA Drug Development Pipeline

FARA believes that there are many different approaches to treating Friedreich’s ataxia, and that it will require a cocktail approach of two or more treatments to slow, stop, reverse, and cure FA. Learn more about the approach behind this potential treatment and explore the other approaches that are in the FA Drug Development pipeline.