Cardiac Output and Fatigue in Friedreich's Ataxia

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorScott Barbuto

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Genetically confirmed FRDA

Ability to safely ride a stationary bicycle (mFARS sitting posture sub-score <2)

Disqualifiers

Beck depression score >19, a score that precludes ability to exercise.30,31

Montreal Cognitive Assessment (MoCA) score <23/30.32

Disorders that interfere with ability to perform endurance exercise (e.g., stroke, respiratory problems, traumatic brain injury, or neuromuscular disease).

Regular participation in vigorous endurance exercise (defined as >2 days/week for at least the past 4 months at max HR>65%).

Trial design

Design model

Parallel

Treatments tested in this trial

  • Aerobic Exercise

    Behavioral

    Both groups will receive aerobic training. The difference will be whether individuals are on or off omaveloxolone.

  • Omeveloxolone

    Drug

    Standard of care treatment for Friedreich's Ataxia

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Home Aerobic Training on OmaveloxoloneExperimental treatment 2 interventions
Group B: Home Aerobic Training off OmaveloxoloneActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Adverse events (Primary outcome for Aim 1)

Adverse events are defined as exercise-related discomforts (muscle and joint pain), minor injuries (strains, sprains), and non-injurious falls. Serious adverse events are defined as hospitalization, surgery, death, or permanent disability. We will compare adverse and serious adverse events for both groups.

Time frame
0, 3, 6 months
2

Maximal Oxygen Consumption (primary outcome measure for Aim 2)

Maximal oxygen consumption (VO2max) will be determined by a breath-by-breath measurement of VO2 with a Vmax Encore Metabolic System, while participants perform a progressive ramped exercise test using an electronic-braked lower body cycle ergometer (CareFusion Corp, San Diego, CA). The minimal clinically important difference (MCID) has been determined to be between 1.0-2.0 mL/kg/min.

Time frame
0, 3-, 6-months
3

Fatigue Severity scale (primary outcome measure for Aim 3)

A commonly used measure to assess fatigue in a variety of populations. A score change of 3.5 to 4.5 points is considered clinically meaningful.

Time frame
0, 3-, and 6-months

Secondary outcomes

1

6-Minute Walk Test

A functional measure of exercise capacity, we will measure the maximum distance a participant can walk in 6 minutes over a 25-meter linear course. The MCID has been determined to be between 14.0 and 30.5 meters. Fatigability will be assessed comparing the distance traveled during the last minute compared to the first minute. This difference will be divided by distance walked in the first minute and expressed as a percentage.

Time frame
0, 3-, and 6-months
2

Fatigue Impact Scale

This scale assesses the perceived impact of fatigue on physical, cognitive, and psychosocial functioning during the participant's past four weeks. An MCID of 3.9 to 8.1 has been determined for other movement disorders such as Parkinson's Disease and Multiple Sclerosis.

Time frame
0, 3-, 6-months
3

Cardiac Output

PhysioFlow is a non-invasive device that allows you to determine cardiac output through impedence cardiography. It is FDA approved to determine cardiac output. Cardiac output will be determined both at rest and at maximal exertion during CPET testing.

Time frame
0, 3-, and 6-months
4

Timed Up and Go

To monitor balance and gait, TUG will be performed three times using the standard protocol, and the results will be averaged. Participants will be instructed to perform this test using the typical assistive device they use to walk outside if applicable. This test has been shown to be a reliable measure of balance in individuals with ataxia.

Time frame
0, 3-, and 6-months

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Scott Barbuto

Lead sponsor

Columbia University

Sponsor institution

Biogen

Collaborator

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