Cardiac Output and Fatigue in Friedreich's Ataxia

NCT07444333 | Not Yet Recruiting DMC

• 2 other identifiers: AAAV7687US-SKY-12378
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Friedreich's Ataxia

Keywords

Friedreich's ataxia; Aerobic exercise; Omaveloxolone; Fatigue; Cardiac Output

Outcome Measures

Primary Outcomes (3)

• 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.

  0, 3, 6 months

• 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.

  0, 3-, 6-months

• 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.

  0, 3-, and 6-months

Secondary Outcomes (7)

• 6-Minute Walk Test

  0, 3-, and 6-months

• Fatigue Impact Scale

  0, 3-, 6-months

• Cardiac Output

  0, 3-, and 6-months

• Timed Up and Go

  0, 3-, and 6-months

• Gait Speed

  0, 3-, 6-months

Study Arms (2)

Home Aerobic Training on Omaveloxolone

EXPERIMENTAL

Participants will be given a recumbent exercise bike (Marcy ME-709 Adjustable Recumbent Exercise Bike, Pomona, CA) for home use. They will be instructed to exercise five times a week. The regimen will include 5-minute warm up, 30 minutes of exercise at target heart rate, and 5 minutes of cool down.

Behavioral: Aerobic Exercise; Drug: Omeveloxolone

Home Aerobic Training off Omaveloxolone

ACTIVE COMPARATOR

Participants will be given a recumbent exercise bike (Marcy ME-709 Adjustable Recumbent Exercise Bike, Pomona, CA) for home use. They will be instructed to exercise five times a week. The regimen will include 5-minute warm up, 30 minutes of exercise at target heart rate, and 5 minutes of cool down.

Behavioral: Aerobic Exercise

Interventions

Aerobic Exercise BEHAVIORAL

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

Home Aerobic Training off Omaveloxolone; Home Aerobic Training on Omaveloxolone

Omeveloxolone DRUG

Standard of care treatment for Friedreich's Ataxia

Home Aerobic Training on Omaveloxolone

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Genetically confirmed FRDA
• Ability to safely ride a stationary bicycle (mFARS sitting posture sub-score \<2)

You may not qualify if:

• 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%).
• Evidence of serious arrhythmias or ischemic heart disease.

Sponsors & Collaborators

• Scott Barbuto: lead
• Biogen: collaborator

MeSH Terms

Conditions

Friedreich Ataxia; Fatigue

Interventions

Exercise

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Scott Barbuto, MD PhD

CONTACT

12123054818; sb3779@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor at Columbia University Medical Center

Model Details: This is a clinical trial examining to impact of aerobic training plus omaveloxolone in FRDA. Thirty individuals with FRDA will be recruited; 20 individuals will be on omaveloxolone treatment whereas the other ten individuals will not. Individuals will undergo baseline assessment including cardiopulmonary exercise testing (CPET), mFARS, gait speed, Timed Up and Go (TUG), Fatigue Severity Scale (FSS), Fatigue Impact Scale (FIS), and 6-minute Walk Test (6MWT). Individuals will then perform 3-months of home aerobic training. Repeat assessments will be conducted at 3- and 6-months.

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: March 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: It will be avaiable after study completion around 12/14/2027
• Access Criteria: They will have access to the study protocol and de-identifed data. It will be deposited in an NIH database.