Natural history: Longitudinal observation of neuroimaging, clinical, and blood markers.
Study summary
This is a natural history study prospectively investigating neuroimaging markers of disease progression in children and adults with Friedreich ataxia (FA). There will be three assessment periods (baseline, 12 and 24 months). The study will include approximately 200 individuals with FA and 100 matched controls recruited across the six international academic sites. Other assessments will include secondary clinical and cognitive markers, as well as exploratory blood markers.
Eligibility
Sex
ALL
Min age
5 Years
Max age
—
Healthy volunteers
Accepted
Inclusion Criteria:
* Age ≥ 5 years
* Written informed consent provided
* Individuals with FA must have a genetic confirmation of diagnosis and be biallelic for a GAA repeat length \> 55 in intron 1 of FXN and/or have a GAA repeat length \> 55 in intron 1 of FXN in one allele and another type of mutation that is inferred to cause loss of function in the second FXN allele
* Individuals with FA must have an age of disease onset ≤ 25 years
* Individuals with FA must have a disease duration ≤ 25 years
* Individuals with FA must have a Friedreich Ataxia Rating Scale (FARS) Functional staging score of ≤ 5 and total modified FARS (mFARS) score of ≤ 65 on enrolment
Exclusion Criteria:
* Age \< 5 years
* Unable to provide written informed consent
* Magnetic resonance contraindications (e.g. pacemaker or other metallic surgical implants)
* Presence of metallic dental braces
* Pregnancy (ascertained via a question or test as mandated at particular sites)
* Individuals with FA must not have acute or ongoing medical or other conditions that, after discussion between the Site Investigator and steering committee, is deemed to interfere with the conduct and assessments of the study
* Individuals with FA must not have another neurological condition apart from FA
* Individuals with FA must not have other neurologic conditions that, in the opinion of the Site Investigator, would interfere with the conduct and assessments of the study
* Controls must not have a diagnosed psychiatric or neurological condition
* Controls must not have acute or ongoing medical or other conditions that would interfere with the conduct and assessments of the study
* Controls must not be siblings of individuals with FA whose carrier status (i.e., confirmed carrier, confirmed non-carrier, or obligate carrier) is unknown.
Primary outcome measure(s)
Baseline dentate nuclei magnetic susceptibility — Baseline Magnetic susceptibility of the dentate nuclei will be measured using T2\*-weighted multiecho magnetic resonance imaging and quantitative susceptibility mapping processing. Baseline dentate nuclei susceptibility will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in dentate nuclei magnetic susceptibility — Baseline to 24 months Magnetic susceptibility of the dentate nuclei will be measured using T2\*-weighted multiecho magnetic resonance imaging and quantitative susceptibility mapping processing. The within-person slope of dentate nuclei susceptibility over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline dentate volume — Baseline Volume of the dentate nuclei will be measured using T2\*-weighted multiecho magnetic resonance imaging and quantitative susceptibility mapping processing. Baseline dentate nuclei volume will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in dentate volume — Baseline to 24 months Volume of the dentate nuclei will be measured using T2\*-weighted multiecho magnetic resonance imaging and quantitative susceptibility mapping processing. The within-person slope of dentate nuclei volume over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline total cerebellar volume — Baseline Total volume of the cerebellum will be measured using T1- and T2-weighted magnetic resonance imaging. Baseline total cerebellar volume will be compared between the Friedreich ataxia and control groups.
Slope of change in total cerebellar volume — Baseline to 24 months Total volume of the cerebellum will be measured using T1- and T2-weighted magnetic resonance imaging. The within-person slope of total cerebellar volume over the three study visits will be estimated and compared between the Friedreich ataxia and control groups.
Baseline superior cerebellar peduncle volume — Baseline Volume of the superior cerebellar peduncles will be measured using T1- and T2-weighted magnetic resonance imaging. Baseline superior cerebellar peduncle volume will be compared between the Friedreich ataxia and control groups.
Slope of change in superior cerebellar peduncle volume — Baseline to 24 months Volume of the superior cerebellar peduncles will be measured using T1- and T2-weighted magnetic resonance imaging. The within-person slope of superior cerebellar peduncle volume over the three study visits will be estimated and compared between the Friedreich ataxia and control groups.
Baseline superior cerebellar peduncle fractional anisotropy — Baseline Fractional anisotropy of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. Baseline superior cerebellar peduncle fractional anisotropy will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in superior cerebellar peduncle fractional anisotropy — Baseline to 24 months Fractional anisotropy of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of superior cerebellar peduncle fractional anisotropy over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline superior cerebellar peduncle mean diffusivity — Baseline Mean diffusivity of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. Baseline superior cerebellar peduncle mean diffusivity will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in superior cerebellar peduncle mean diffusivity — Baseline to 24 months Mean diffusivity of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of superior cerebellar peduncle mean diffusivity over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline superior cerebellar peduncle radial diffusivity — Baseline Radial diffusivity of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. Baseline superior cerebellar peduncle radial diffusivity will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in superior cerebellar peduncle radial diffusivity — Baseline to 24 months Radial diffusivity of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of superior cerebellar peduncle radial diffusivity over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline superior cerebellar peduncle axial diffusivity — Baseline Axial diffusivity of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. Baseline superior cerebellar peduncle axial diffusivity will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in superior cerebellar peduncle axial diffusivity — Baseline to 24 months Axial diffusivity of the superior cerebellar peduncles will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of superior cerebellar peduncle axial diffusivity over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline cervical spinal cord cross-sectional area — Baseline Cross-sectional area of the cervical portion of the spinal cord will be measured using T2-weighted magnetic resonance imaging. Baseline cervical spinal cord cross-sectional area will be compared between the Friedreich ataxia and control groups.
Slope of change in cervical spinal cord cross-sectional area — Baseline to 24 months Cross-sectional area of the cervical portion of the spinal cord will be measured using T2-weighted magnetic resonance imaging. The within-person slope of cervical spinal cord cross-sectional area over the three study visits will be estimated and compared between the Friedreich ataxia and control groups.
Baseline cervical spinal cord fractional anisotropy — Baseline Fractional anisotropy of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. Baseline cervical spinal cord fractional anisotropy will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in cervical spinal cord fractional anisotropy — Baseline to 24 months Fractional anisotropy of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of cervical spinal cord fractional anisotropy over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline cervical spinal cord mean diffusivity — Baseline Mean diffusivity of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. Baseline cervical spinal cord mean diffusivity will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in cervical spinal cord mean diffusivity — Baseline to 24 months Mean diffusivity of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of cervical spinal cord mean diffusivity over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline cervical spinal cord radial diffusivity — Baseline Radial diffusivity of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. Baseline cervical spinal cord radial diffusivity will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in cervical spinal cord radial diffusivity — Baseline to 24 months Radial diffusivity of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of cervical spinal cord radial diffusivity over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline cervical spinal cord axial diffusivity — Baseline Axial diffusivity of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. Baseline cervical spinal cord axial diffusivity will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of change in cervical spinal cord axial diffusivity — Baseline to 24 months Axial diffusivity of the cervical portion of the spinal cord will be measured using diffusion tensor magnetic resonance imaging. The within-person slope of cervical spinal cord axial diffusivity over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Baseline cervical spine tNAA/mIns ratio — Baseline The ratio of N-acetylaspartate (tNAA) and myo-inositol (mIns) within cervical spinal cord will be measured using sLASER magnetic resonance spectroscopy. The baseline tNAA/mIns ratio will be compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Slope of the cervical spine tNAA/mIns ratio — Baseline to 24 months The ratio of N-acetylaspartate (tNAA) and myo-inositol (mIns) within cervical spinal cord will be measured using sLASER magnetic resonance spectroscopy. The within-person slope of the tNAA/mIns ratio over the three study visits will be estimated and compared between the Friedreich ataxia and control groups. This measurement will be obtained for participants aged 11 years and over.
Trial sites (7)
Facility
City
Region
Status
University of Florida
Gainesville
Florida
Center for Magnetic Resonance Research, University of Minnesota
Minneapolis
Minnesota
Children's Hospital of Philadelphia
Philadelphia
Pennsylvania
Monash Biomedical Imaging, Monash University
Clayton
Victoria
Lab of Neuroimaging and Dept of Neurology, University of Campinas (UNICAMP)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.