Early and Longitudinal Assessment of Neurodegeneration in the Brain and Spinal Cord in Friedreich's Ataxia

Friedreich's ataxia is characterized by progressive alterations in the function of the cerebellum accompanied by an atrophy of the spinal cord. Although the genetic defect responsible for the disease has been identified more than 15 years ago, objective markers of the pathologic process (i.e., biomarkers) that would allow measuring the effects of potential therapies are still lacking. Moreover, it is still unclear how the malfunction of the cerebellum affects the rest of the brain, and understanding the connectivity and neurochemistry of the central nervous system might yield new insights in the understanding of the disease, in addition to providing potential markers.

To address these needs, the investigators aim at utilizing the capabilities of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS). Using techniques called Diffusion Imaging, resting-state functional MRI, and Proton Spectroscopy (1H MRS), the investigators propose to determine the differences in the connectivity and neurochemistry of the spinal cord and the brain between patients affected by Friedreich's ataxia and healthy controls. The investigators plan on imaging both patients and control subjects using a 3T magnet, a system that although not yet available in all medical facilities, is becoming standard in most hospitals and clinics. The first aim is to scan patients already scanned last year (12-month follow-up). The second aim is to scan patients at an early stage of the disease.

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia

• Study Type: Observational
• Enrollment (Actual): 85

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Friedreich's ataxia at the early stage of the disease (e.g. ambulatory and not wheelchair bound and no to early cardiomyopathy) Age- and gender-matched healthy volunteers

Description

Inclusion Criteria:

• Genetic diagnosis of Friedreich's ataxia for patient volunteers with GAA repeat expansion number
• Absence of neurological conditions for control volunteers
• Control volunteers will be age-, race-, and gender-matched to the patients

Exclusion Criteria:

• Claustrophobia
• Smoking
• Diabetes
• Pregnancy or lactation
• Weight over 300 lbs
• Presence of a pacemaker or any paramagnetic object in the body
• Severe scoliosis

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patient with FRDA; Patients affected by Friedreich's ataxia
Healthy controls; Healthy volunteers age- and gender-matched with no neurological disease identified.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in connectivity (apparent coefficient of diffusion, fractional anisotropy, radial and axial diffusivity), anatomy (cortical thickness, volumetry analysis) and biochemistry (metabolite concentrations) between patients and controls	The investigators will look at the differences between patients and controls. This is observational, not interventional. The fractional anisotropy (FA) is a scalar value. The apparent coefficient of diffusion, radial and axial diffusivity are measured in mm2/s. The metabolite concentrations in the brain are in the order of µg/ g wet tissue weight. Cortical thickness is measured in mm.	1 year

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Friedreich's Ataxia Research Alliance; Bob Allison Ataxia Research Center
• Investigators: Principal Investigator: Pierre-Gilles Henry, Ph.D., University of Minnesota; Principal Investigator: Christophe Lenglet, Ph.D, University of Minnesota

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): February 8, 2022
• Study Completion (Actual): February 8, 2022

Study Registration Dates

• First Submitted: January 14, 2013
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (Estimate): January 28, 2013

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: cerebellum; FRDA; ataxia; recessive; FA; Friedreich; neurodegenerative
• Additional Relevant MeSH Terms: Pathologic Processes; 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; Nerve Degeneration
• Other Study ID Numbers: 1210M22281