Biomarkers in Friedreich's Ataxia

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.

Study Overview

• Status: Recruiting
• Conditions: 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 Type: Observational
• Enrollment (Estimated): 203

Contacts and Locations

• Study Contact: Name: Mackenzi Coker, M.S.CCC-SLP; Phone Number: 352-294-8754; Email: mcoker@peds.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Contact: Mackenzi Coker, MS, CCC-SLP; Phone Number: 352-273-8754; Email: mcoker@ufl.edu
      • Sub-Investigator: Sub Subramony, MD
      • Principal Investigator: Manuela Corti, PT, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 68 years (Child, Adult, Older Adult)
• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac MRI	Cardiac MRI will be used to characterize cardiac morphology and function.	Baseline and Follow-Up Visits
Echocardiogram	Echocardiogram will be used to characterize cardiac morphology and function.	Baseline and Follow-Up Visits
Friedreich's Ataxia Rating Scale (FARS)	FARS scores describe specific neurological impairments in FA.	Baseline and Follow-Up Visits
Metabolic exercise testing	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.	Baseline and Follow-Up Visits
Scale for the Assessment and Rating of Ataxia (SARA)	Clinical scale assessing impairment levels in cerebellar ataxia	Baseline and Follow-Up Visits
Muscle Biopsy	The muscle sample will be used to evaluate Frataxin quantification	Baseline
Skin Biopsy	Analyses to peripheral tissue used to find out how Friedreich's Ataxia develops.	Baseline
9-Hole-Peg Test	Assesses upper extremity function and motor coordination.	Baseline and Follow-Up Visits
Pulmonary Function Testing	Breathing tests to assess lung strength and function.	Baseline and Follow-Up Visits

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institutes of Health (NIH); National Center for Advancing Translational Sciences (NCATS); Children's Miracle Network
• Investigators: Principal Investigator: Manuela Corti, PT, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Estimated): June 3, 2030
• Study Completion (Estimated): June 3, 2030

Study Registration Dates

• First Submitted: July 7, 2015
• First Submitted That Met QC Criteria: July 9, 2015
• First Posted (Estimated): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: neuromuscular; ataxia
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia
• Other Study ID Numbers: IRB201500369-N; UL1TR000064 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No