Cardiac Output and Fatigue in Friedreich's Ataxia

AIM 1: Acceptability and Feasibility of Home Aerobic Exercise. Individuals with other types of ataxia have been able to train at the above levels safely. We hypothesize that there will be no serious adverse events related to aerobic training, and there will be an acceptable number of minor adverse events. We further hypothesize that drop-out from the trial will be less than 25%.

AIM 2: Impact of Omaveloxolone on VO2max. Omaveloxolone works by activating and preventing the degradation of Nuclear factor-like 2 (Nrf2), which helps prevent oxidative damage within the mitochondria of individuals with FRDA. Improved mitochondrial function should significantly enhance VO2max by increasing ATP production and improving the rate of oxygen consumption. Thus, we hypothesize that individuals on omaveloxolone will have a significantly larger increase in VO2max after the aerobic training when compared to individuals who are not on omaveloxolone.

AIM 3: Impact of Aerobic Training + Omaveloxolone on Fatigue. Omaveloxolone has been shown to cause a transient (12-week) increase in fatigue. Aerobic training, on the other hand, is known to improve fatigue in individuals with other hereditary ataxias. For this aim, the primary outcome measure will be the Fatigue Severity Scale (FSS) with secondary measures of Fatigue Impact Scale (FIS) and 6-minute walk test (6MWT). We hypothesize improved fatigue with the incorporation of aerobic training and that individuals in the omaveloxolone group will have less fatigue than those not on omaveloxolone.