NCT04349514

Brief 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.

Trial Health

62
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2021

Longer than P75 for all trials

Geographic Reach
5 countries

7 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 1, 2020

Completed
15 days until next milestone

First Posted

Study publicly available on registry

April 16, 2020

Completed
10 months until next milestone

Study Start

First participant enrolled

February 10, 2021

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2025

Completed
Last Updated

November 27, 2024

Status Verified

October 1, 2024

Enrollment Period

4.6 years

First QC Date

April 1, 2020

Last Update Submit

November 25, 2024

Conditions

Friedreich Ataxia

Keywords

NeuroimagingLongitudinalBiomarkersNatural history

Outcome Measures

Primary Outcomes (28)

  • Baseline dentate nuclei magnetic susceptibility

    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.

    Baseline

  • Slope of change in dentate nuclei magnetic susceptibility

    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 to 24 months

  • Baseline dentate volume

    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.

    Baseline

  • Slope of change in dentate volume

    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 to 24 months

  • Baseline total cerebellar volume

    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.

    Baseline

  • Slope of change in total cerebellar volume

    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 to 24 months

  • Baseline superior cerebellar peduncle volume

    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.

    Baseline

  • Slope of change in superior cerebellar peduncle volume

    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 to 24 months

  • Baseline superior cerebellar peduncle fractional anisotropy

    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.

    Baseline

  • Slope of change in superior cerebellar peduncle fractional anisotropy

    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 to 24 months

  • Baseline superior cerebellar peduncle mean diffusivity

    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.

    Baseline

  • Slope of change in superior cerebellar peduncle mean diffusivity

    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 to 24 months

  • Baseline superior cerebellar peduncle radial diffusivity

    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.

    Baseline

  • Slope of change in superior cerebellar peduncle radial diffusivity

    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 to 24 months

  • Baseline superior cerebellar peduncle axial diffusivity

    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.

    Baseline

  • Slope of change in superior cerebellar peduncle axial diffusivity

    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 to 24 months

  • Baseline cervical spinal cord cross-sectional area

    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.

    Baseline

  • Slope of change in cervical spinal cord cross-sectional area

    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 to 24 months

  • Baseline cervical spinal cord fractional anisotropy

    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.

    Baseline

  • Slope of change in cervical spinal cord fractional anisotropy

    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 to 24 months

  • Baseline cervical spinal cord mean diffusivity

    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.

    Baseline

  • Slope of change in cervical spinal cord mean diffusivity

    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 to 24 months

  • Baseline cervical spinal cord radial diffusivity

    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.

    Baseline

  • Slope of change in cervical spinal cord radial diffusivity

    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 to 24 months

  • Baseline cervical spinal cord axial diffusivity

    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.

    Baseline

  • Slope of change in cervical spinal cord axial diffusivity

    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 to 24 months

  • Baseline cervical spine tNAA/mIns ratio

    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.

    Baseline

  • Slope of the cervical spine tNAA/mIns ratio

    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.

    Baseline to 24 months

Secondary Outcomes (13)

  • Modified Friedreich Ataxia Rating Scale (mFARS) score

    Baseline to 24 months

  • Upright Stability (US) score

    Baseline to 24 months

  • Activities of Daily Living (ADL) score

    Baseline to 24 months

  • Scale for the Assessment and Rating of Ataxia (SARA) score

    Baseline to 24 months

  • 9 Hole Peg Test times

    Baseline to 24 months

  • +8 more secondary outcomes

Other Outcomes (2)

  • Serum neurofilament light chain (NfL) level

    Baseline to 24 months

  • Frataxin protein level

    Baseline to 24 months

Study Arms (2)

Friedreich ataxia

Individuals with a diagnosis of Friedreich ataxia.

Other: Natural history

Control

Individuals without a diagnosis of Friedreich ataxia.

Other: Natural history

Interventions

Natural historyOTHER

Longitudinal observation of neuroimaging, clinical, and blood markers.

ControlFriedreich ataxia

Eligibility Criteria

Age5 Years+
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The study population will consist of individuals aged 5 and above who either have a diagnosis of Friedreich ataxia (FA) or who do not (Controls). Controls will be healthy volunteers who are age- and gender-matched to the FA cohort.

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

University of Florida

Gainesville, Florida, 32611, United States

Location

Center for Magnetic Resonance Research, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Monash Biomedical Imaging, Monash University

Clayton, Victoria, 3168, Australia

Location

Lab of Neuroimaging and Dept of Neurology, University of Campinas (UNICAMP)

São Paulo, São Paulo, Brazil

Location

McGill University

Montreal, Quebec, H3A 2B4, Canada

Location

Department of Neurology, RWTH Aachen University

Aachen, Germany

Location

Related Publications (4)

  • Shiraishi DH, Saha S, Adanyeguh IM, Cocozza S, Corben LA, Deistung A, Delatycki MB, Dogan I, Gaetz W, Georgiou-Karistianis N, Graf S, Grisoli M, Henry PG, Jarola GM, Joers JM, Langkammer C, Lenglet C, Li J, Lobo CC, Lock EF, Lynch DR, Mareci TH, Martinez ARM, Monti S, Nigri A, Pandolfo M, Reetz K, Roberts TP, Romanzetti S, Rudko DA, Scaravilli A, Schulz JB, Subramony SH, Timmann D, Franca MC, Harding IH, Rezende TJR; TRACK-FA Neuroimaging Consortium. Automated Deep Learning-based Segmentation of the Dentate Nucleus Using Quantitative Susceptibility Mapping MRI. Radiol Artif Intell. 2025 Nov;7(6):e240478. doi: 10.1148/ryai.240478.

    PMID: 40767617DERIVED

  • Georgiou-Karistianis N, Corben LA, Lock EF, Bujalka H, Adanyeguh I, Corti M, Deelchand DK, Delatycki MB, Dogan I, Farmer J, Franca MC Jr, Gabay AS, Gaetz W, Harding IH, Joers J, Lax MA, Li J, Lynch DR, Mareci TH, Martinez ARM, Pandolfo M, Papoutsi M, Parker RG, Reetz K, Rezende TJR, Roberts TP, Romanzetti S, Rudko DA, Saha S, Schulz JB, Subramony SH, Supramaniam VG, Lenglet C, Henry PG. Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study. Ann Neurol. 2025 Aug;98(2):386-397. doi: 10.1002/ana.27237. Epub 2025 Mar 22.

    PMID: 40119735DERIVED

  • Georgiou-Karistianis N, Corben LA, Reetz K, Adanyeguh IM, Corti M, Deelchand DK, Delatycki MB, Dogan I, Evans R, Farmer J, Franca MC, Gaetz W, Harding IH, Harris KS, Hersch S, Joules R, Joers JJ, Krishnan ML, Lax M, Lock EF, Lynch D, Mareci T, Muthuhetti Gamage S, Pandolfo M, Papoutsi M, Rezende TJR, Roberts TPL, Rosenberg JT, Romanzetti S, Schulz JB, Schilling T, Schwarz AJ, Subramony S, Yao B, Zicha S, Lenglet C, Henry PG. A natural history study to track brain and spinal cord changes in individuals with Friedreich's ataxia: TRACK-FA study protocol. PLoS One. 2022 Nov 21;17(11):e0269649. doi: 10.1371/journal.pone.0269649. eCollection 2022.

    PMID: 36410013DERIVED

  • Hernandez ALCC, Rezende TJR, Martinez ARM, de Brito MR, Franca MC Jr. Tract-Specific Spinal Cord Diffusion Tensor Imaging in Friedreich's Ataxia. Mov Disord. 2022 Feb;37(2):354-364. doi: 10.1002/mds.28841. Epub 2021 Oct 29.

    PMID: 34713932DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

A blood sample (approximately 18-20ml) will be collected from each participant at the first assessment by a trained phlebotomist or clinician and processed immediately by research staff.

MeSH Terms

Conditions

Friedreich Ataxia

Condition Hierarchy (Ancestors)

Spinocerebellar DegenerationsCerebellar DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesSpinal Cord DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMitochondrial DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Nellie Georgiou-Karistianis, PhD

    Monash University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor Nellie Georgiou-Karistianis

Study Record Dates

First Submitted

April 1, 2020

First Posted

April 16, 2020

Study Start

February 10, 2021

Primary Completion

October 1, 2025

Study Completion

October 1, 2025

Last Updated

November 27, 2024

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will share

It is recognised that this project will generate data that is of interest to the FA academic and bio-pharmaceutical, drug development community. All such data (de-identified) will be made available to third parties at the completion of the study after request, with approval from the TRACK-FA Steering Committee. Each site will be required to ensure that participants are consented in such a way that allows the sharing of de-identified data with the community in this manner.

Time Frame
Data will become available after the conclusion of the TRACK-FA study. The study will be 5 years in duration and each academic site may have a slightly different start and end date.
Access Criteria
Data access will be granted on a case-by-case basis after the study has been completed. The requesting party will be required to submit a formal request to the TRACK-FA Steering Committee outlining how the data is to be used and for what purpose.
More information

Locations

CA(1)US(3)AU(1)DE(1)BR(1)