Biomarkers in Friedreich's Ataxia

• ClinicalTrials.gov Identifier: NCT02497534
• Recruitment Status: Recruiting
• First Posted: July 14, 2015
• Last Update Posted: April 26, 2022
• Sponsor: University of Florida
• Collaborators: Children's Miracle Network; National Institutes of Health (NIH)
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

The purpose of this project is to characterize measures of cardiac performance and neuromuscular physiology in FA patients using novel techniques, including echocardiography and magnetic resonance imaging (MRI), metabolic exercise testing, and neurophysiological outcomes.

Condition or disease
Friedreich's Ataxia

Detailed Description:

Friedreich's ataxia (FA) is an autosomal recessive disease caused by a mutation in the frataxin gene (FXN). Although rare, FA is the most common form of hereditary ataxia, affecting 1 in every 50,000 people in the United States. Currently, palliative therapies are the only treatment for FA patients. However, current gene therapy efforts in other neuromuscular diseases have positioned the investigator's research program to extend these discoveries and techniques to FA. As new therapies become available for clinical application, it is crucial to identify non-invasive outcomes measures of cardiac and neuromuscular performance with adequate sensitivity to detect the impact of treatments.

Study Design

• Study Type: Observational
• Estimated Enrollment: 203 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Biomarkers in Friedreich's Ataxia
• Study Start Date: September 2015
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2022

Groups and Cohorts

Group/Cohort
Affected with Friedreich's ataxia; Friedreich's ataxia patients aged 8 to 70 (inclusive). Assessments will include collection of genetic mutation reports, cardiac and exercise MRI, echocardiogram, the Friedreich's Ataxia Rating Scale (FARS), exercise testing with a recombinant bike and/or hand ergometer, pulmonary function testing, and gait analysis. Optional labs include a blood draw, skin biopsy, and/or muscle biopsy.
Healthy controls; Health controls aged 8 to 70 (inclusive). Assessments will include cardiac and exercise MRI, echocardiogram, the Friedreich's Ataxia Rating Scale (FARS), exercise testing, hand ergometer for exercise testing, pulmonary function testing, gait analysis, and an optional blood draw.
Carriers of Friedreich's ataxia; An obligate carrier aged 18 to 70 (inclusive) of the abnormal Friedreich's ataxia gene by being a parent of a child with Friedreich's ataxia. No assessments are to be conducted. Optional labs include a blood draw, skin biopsy, and/or muscle biopsy.

Outcome Measures

Primary Outcome Measures :

1. Cardiac MRI [ Time Frame: Baseline and Follow-Up Visits ]
   Cardiac MRI will be used to characterize cardiac morphology and function.
2. Echocardiogram [ Time Frame: Baseline and Follow-Up Visits ]
   Echocardiogram will be used to characterize cardiac morphology and function.
3. Friedreich's Ataxia Rating Scale (FARS) [ Time Frame: Baseline and Follow-Up Visits ]
   FARS scores describe specific neurological impairments in FA.
4. Metabolic exercise testing [ Time Frame: Baseline and Follow-Up Visits ]
   Metabolic exercise testing will be performed on either a recumbent bike or hand ergometer and will measure the maximal amount of exercise the subject is able to perform.
5. Scale for the Assessment and Rating of Ataxia (SARA) [ Time Frame: Baseline and Follow-Up Visits ]
   Clinical scale assessing impairment levels in cerebellar ataxia
6. Muscle Biopsy [ Time Frame: Baseline ]
   The muscle sample will be used to evaluate Frataxin quantification
7. Skin Biopsy [ Time Frame: Baseline ]
   Analyses to peripheral tissue used to find out how Friedreich's Ataxia develops.
8. 9-Hole-Peg Test [ Time Frame: Baseline and Follow-Up Visits ]
   Assesses upper extremity function and motor coordination.
9. Pulmonary Function Testing [ Time Frame: Baseline and Follow-Up Visits ]
   Breathing tests to assess lung strength and function.

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Subjects with Friedreich's ataxia, healthy control subjects, and carriers of Friedreich's ataxia

Criteria

Inclusion Criteria:

• Genetic diagnosis of Friedreich's ataxia by DNA sequencing, mutational analysis or protein assay OR be a healthy subject with no evidence of a neuromuscular disorder
• Between the ages of 8 and 70 (inclusive)
• Are able to tolerate metabolic exercise testing
• Are stable on cardiac medication regimen for 3 months prior to screening

Exclusion Criteria:

• Presence of unstable heart disease
• Receipt of cardiac transplant
• Any concurrent medical condition which, in the opinion of the investigators, would make the subject unsuitable for the study

Contacts and Locations

Contacts

Contact: Samantha Norman, MPH, BS; 352-273-8218; samantha.norman@peds.ufl.edu

Locations

United States, Florida

University of Florida; Recruiting

Gainesville, Florida, United States, 32610

Contact: Mackenzi Coker, MS, CCC-SLP 352-273-8754 mcoker@ufl.edu

Principal Investigator: Manuela Corti, PT, PhD

Sub-Investigator: Sub Subramony, MD

Sponsors and Collaborators

University of Florida

Children's Miracle Network

National Institutes of Health (NIH)

Investigators

• Principal Investigator: Manuela Corti, PT, PhD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02497534
• Other Study ID Numbers: IRB201500369-N; UL1TR000064 ( U.S. NIH Grant/Contract )
• First Posted: July 14, 2015
• Last Update Posted: April 26, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:

ataxia; neuromuscular

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases