Ignite Creation Date:
2026-03-26 @ 3:19 PM
Ignite Modification Date:
2026-03-31 @ 3:17 AM
Study NCT ID:
NCT07444333
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-02
First Post:
2025-11-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cardiac Output and Fatigue in Friedreich's Ataxia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005621', 'term': 'Friedreich Ataxia'}, {'id': 'D005221', 'term': 'Fatigue'}], 'ancestors': [{'id': 'D013132', 'term': 'Spinocerebellar Degenerations'}, {'id': 'D002526', 'term': 'Cerebellar Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D013118', 'term': 'Spinal Cord Diseases'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D028361', 'term': 'Mitochondrial Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015444', 'term': 'Exercise'}], 'ancestors': [{'id': 'D009043', 'term': 'Motor Activity'}, {'id': 'D009068', 'term': 'Movement'}, {'id': 'D009142', 'term': 'Musculoskeletal Physiological Phenomena'}, {'id': 'D055687', 'term': 'Musculoskeletal and Neural Physiological Phenomena'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2028-04-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-26', 'studyFirstSubmitDate': '2025-11-17', 'studyFirstSubmitQcDate': '2026-02-26', 'lastUpdatePostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-02-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Adverse events (Primary outcome for Aim 1)', 'timeFrame': '0, 3, 6 months', 'description': '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.'}, {'measure': 'Maximal Oxygen Consumption (primary outcome measure for Aim 2)', 'timeFrame': '0, 3-, 6-months', 'description': '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.'}, {'measure': 'Fatigue Severity scale (primary outcome measure for Aim 3)', 'timeFrame': '0, 3-, and 6-months', 'description': '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.'}], 'secondaryOutcomes': [{'measure': '6-Minute Walk Test', 'timeFrame': '0, 3-, and 6-months', 'description': '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.'}, {'measure': 'Fatigue Impact Scale', 'timeFrame': '0, 3-, 6-months', 'description': "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."}, {'measure': 'Cardiac Output', 'timeFrame': '0, 3-, and 6-months', 'description': '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.'}, {'measure': 'Timed Up and Go', 'timeFrame': '0, 3-, and 6-months', 'description': '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.'}, {'measure': 'Gait Speed', 'timeFrame': '0, 3-, 6-months', 'description': 'Gait Speed will be determined by asking participants to walk as fast as possible on a 10-meter runway three times, and the times will be averaged. The MCID has been determined to be between 0.1m/s to 0.2 m/s for various patient populations.'}, {'measure': 'mFARS', 'timeFrame': '0, 3-, 6-months', 'description': 'mFARS is a validated measure of ataxia symptoms in individuals with FRDA. Scores range from 0-93 points, with higher scores indicating more ataxia. Research has shown the mFARS has good internal consistency, interrater and test-retest reliability. The minimal clinically important difference is not clearly defined, however.'}, {'measure': 'Exercise Adherence', 'timeFrame': '0, 3-, 6-months', 'description': 'We will determine the average number of days per week exercised and duration of the exercise at target heart rate. The measure for achieving levels of exercise intensity is derived from the average heart rate during an exercise session expressed as a percentage of the maximal heart rate for the individual.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ["Friedreich's ataxia", 'Aerobic exercise', 'Omaveloxolone', 'Fatigue', 'Cardiac Output'], 'conditions': ["Friedreich's Ataxia"]}, 'descriptionModule': {'briefSummary': '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%.\n\nAIM 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.\n\nAIM 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.', 'detailedDescription': "In February 2023, omaveloxolone became the first Food and Drug Administration (FDA) approved medication for Friedreich's Ataxia (FRDA). In its pivotal study, named MOXIe, researchers found that omaveloxolone significantly improved neurological function compared to placebo. The primary outcome measure was the modified Friedreich's Ataxia Rating Scale (mFARS), the gold standard for measuring ataxia symptoms in clinical trials for FRDA. However, there are several limitations with the use of mFARS:\n\n1\\) It does not detect subtle disease progression over short time frames. For example, in MOXIe, differences between placebo and omaveloxolone were not detected until 48 weeks. 2) Some of the components of mFARS rely on clinical judgment, which can introduce variability between raters. 3) The minimal clinical important difference (MCID) for mFARS has not been clearly defined. 4) The scale lacks sensitivity to detect changes in individuals with minimal symptoms or advanced disease. Given these limitations, development of additional outcome measures for clinical trials to determine the impact of drugs like omaveloxolone is desirable.In this study, we propose using maximal oxygen consumption (VO2max) as a future primary outcome measure for FRDA clinical trials. VO2max offers several advantages as an outcome measure: 1) It is a direct physiological measure of aerobic capacity, reducing subjectivity compared to clinical scales like mFARS. 2) It can detect subtle changes in aerobic function making it useful for monitoring intervention effects over time. 3) It has a defined MCID, and higher VO2max is associated with better health outcomes making it a clinically meaningful endpoint. 4) It is non-invasive and reproducible.\n\nTo examine the utility of VO2max as a primary outcome measure, we will recruit 30 individuals with FRDA in this pilot study. Twenty individuals will be on omaveloxolone treatment whereas the other 10 individuals will not. Individuals will undergo baseline cardiopulmonary exercise testing (CPET) to determine VO2max. Secondary measures will include cardiac output. All participants will be given a recumbent bicycle for home use. Participants will be expected to cycle 30-minutes per session, 5x per week at 65-75% maximum heart rate (moderate intensity) for 3-months. To track training, individuals will be given a Fitbit Charge 6, and an exercise physiologist will call every two weeks to adjust training as needed. To determine benefits of training with omaveloxolone, repeat assessments will occur at 3- and 6-months.\n\nAIM 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%.\n\nAIM 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.\n\nAIM 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.\n\nClinical Significance: This pilot study will provide the foundation for the use of VO2max as an outcome measure in future FRDA trials. It will also examine the synergistic effect of omaveloxolone and aerobic training which may show greater improvement than either intervention alone, including improvements in fatigue."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Genetically confirmed FRDA\n2. Ability to safely ride a stationary bicycle (mFARS sitting posture sub-score \\<2)\n\nExclusion Criteria:\n\n1. Beck depression score \\>19, a score that precludes ability to exercise.30,31\n2. Montreal Cognitive Assessment (MoCA) score \\<23/30.32\n3. Disorders that interfere with ability to perform endurance exercise (e.g., stroke, respiratory problems, traumatic brain injury, or neuromuscular disease).\n4. Regular participation in vigorous endurance exercise (defined as \\>2 days/week for at least the past 4 months at max HR\\>65%).\n5. Evidence of serious arrhythmias or ischemic heart disease.'}, 'identificationModule': {'nctId': 'NCT07444333', 'briefTitle': "Cardiac Output and Fatigue in Friedreich's Ataxia", 'organization': {'class': 'OTHER', 'fullName': 'Columbia University'}, 'officialTitle': "Cardiac Output and Fatigue in Friedreich's Ataxia", 'orgStudyIdInfo': {'id': 'AAAV7687'}, 'secondaryIdInfos': [{'id': 'US-SKY-12378', 'type': 'OTHER_GRANT', 'domain': 'Biogen'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Home Aerobic Training on Omaveloxolone', 'description': '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.', 'interventionNames': ['Behavioral: Aerobic Exercise', 'Drug: Omeveloxolone']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Home Aerobic Training off Omaveloxolone', 'description': '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.', 'interventionNames': ['Behavioral: Aerobic Exercise']}], 'interventions': [{'name': 'Aerobic Exercise', 'type': 'BEHAVIORAL', 'description': 'Both groups will receive aerobic training. The difference will be whether individuals are on or off omaveloxolone.', 'armGroupLabels': ['Home Aerobic Training off Omaveloxolone', 'Home Aerobic Training on Omaveloxolone']}, {'name': 'Omeveloxolone', 'type': 'DRUG', 'description': "Standard of care treatment for Friedreich's Ataxia", 'armGroupLabels': ['Home Aerobic Training on Omaveloxolone']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Scott Barbuto, MD PhD', 'role': 'CONTACT', 'email': 'sb3779@cumc.columbia.edu', 'phone': '12123054818'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP'], 'timeFrame': 'It will be avaiable after study completion around 12/14/2027', 'ipdSharing': 'YES', 'description': 'Data will be made available upon request', 'accessCriteria': 'They will have access to the study protocol and de-identifed data. It will be deposited in an NIH database.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Scott Barbuto', 'class': 'OTHER'}, 'collaborators': [{'name': 'Biogen', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor at Columbia University Medical Center', 'investigatorFullName': 'Scott Barbuto', 'investigatorAffiliation': 'Columbia University'}}}}