Friedreich Ataxia(TRACK-FA)NCT04349514
A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
An observational study of Friedreich Ataxia, run by Monash University at 7 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 5 years and olderHealthy volunteers can take part
- Conditions the study is for
- Friedreich Ataxia
- What is being tested?
- Natural history
- How many people
- 300 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 10 Feb 2021to Oct 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United States3 sites
University of Florida
Gainesville, Florida, 32611
Center for Magnetic Resonance Research, University of Minnesota
Minneapolis, Minnesota, 55455
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Australia1 site
Monash Biomedical Imaging, Monash University
Clayton, Victoria, 3168
Brazil1 site
Lab of Neuroimaging and Dept of Neurology, University of Campinas (UNICAMP)
São Paulo, São Paulo
About this study
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.
Read the detailed description
Friedreich ataxia (FA) is a multi-system progressive disorder with the most prevalent and prominent symptoms relating to dysfunction in the central and peripheral nervous system, including, loss of balance and coordination, frequent falls, loss of ambulation, dysarthria, dysphagia and loss of vision and hearing. Other symptoms include cardiomyopathy, diabetes, scoliosis and fatigue. Age of onset can vary but most often presents during childhood, ages 5-15 years.
There is currently no cure and no disease-modifying treatment. Drug candidates to potentially treat FA are under development; however, there is a lack of well- characterized neuroimaging biomarkers for testing their efficacy in clinical trials, hampering this process. Establishing disease-specific neuroimaging biomarkers to track disease progression requires high-quality longitudinal data from large cohorts of patients, compared to controls. In rare diseases, such as FA, this can only be achieved through multi-site collaboration.
The aim of TRACK-FA is to develop an FA neuroimaging dataset from brain and spinal cord that is suitable for assessing the potential value of neuroimaging biomarkers and providing a basis for instituting them in clinical trials. The dataset will comprise a range of neuroimaging measures to assess changes in spinal cord and brain regions that have previously shown to be compromised in individuals with FA. In addition to neuroimaging measures, TRACK-FA will also include clinical, cognitive data and biospecimen data. The TRACK-FA dataset will provide a unique opportunity for academic researchers in collaboration with industry partners to access the images, subsidiary data, and associated clinical data for community research.
This multi-centre study is a collaborative effort across six academic institutions, together with industry partners and the Friedreich's Ataxia Research Alliance USA (FARA).
- Conditions
- Friedreich Ataxia
- Being tested
- Natural history
- Keywords
- Neuroimaging, Longitudinal, Biomarkers, Natural history
- Medical subject headings
- Friedreich Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Natural historyOther
Longitudinal observation of neuroimaging, clinical, and blood markers.
| Study group | Role | What they receive |
|---|---|---|
| Friedreich ataxia | Individuals with a diagnosis of Friedreich ataxia. Receives: Other: Natural history | |
| Control | Individuals without a diagnosis of Friedreich ataxia. Receives: Other: Natural history |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 24 months
Secondary outcomes (13)
Modified Friedreich Ataxia Rating Scale (mFARS) score
The modified Friedreich Ataxia Rating Scale (mFARS) is a neurological rating scale comprising four subscales (bulbar, upper limb coordination, lower limb coordination, and upright stability). The total score ranges from 0 to 93, with a higher score reflecting greater neurological severity. This assessment will be administered to participants with FA only.
Measured: Baseline to 24 months
Upright Stability (US) score
The Upright Stability (US) assessment is part of the neurological examination within the Modified Friedreich Ataxia Rating Scale (mFARS). This component comprises nine items: sitting position, stance with feet apart, stance with feet apart and eyes closed, stance with feet together, stance with feet together and eyes closed, tandem stance, stance with dominant foot, tandem walk, and gait. The score ranges from 0 to 9, with a higher score reflecting poorer upright stability (i.e., greater neurological severity). This assessment will be administered to participants with FA only.
Measured: Baseline to 24 months
Activities of Daily Living (ADL) score
Activities of Daily Living (ADL) is a component of the Friedreich Ataxia Rating Scale (FARS), a clinical rating scale developed for FA. The ADL score aims to quantify essential and routine aspects of self-care, often reported on by a family member or caregiver of a person with FA. The ADL comprises 9 items: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. The score ranges from 0 to 36, with a higher score reflecting greater difficulty completing activities of daily living independently. This assessment will be administered to participants with FA only.
Measured: Baseline to 24 months
Scale for the Assessment and Rating of Ataxia (SARA) score
The SARA is a semi-quantitative assessment of ataxia, measuring ataxia of upper limb, lower limb, gait, balance and speech. It has eight items: gait, stance, sitting, speech disturbance, finger chase, nose-finger test, fast alternating hand movement, and heel-shin slide. The total score ranges from 0 (no ataxia) to 40 (severe ataxia). This assessment will be administered to participants with FA only.
Measured: Baseline to 24 months
9 Hole Peg Test times
The 9 Hole Peg Test (9HPT) examines finger dexterity and involves placing and removing nine pegs in a pegboard in the quickest possible time. Two consecutive trials of the dominant hand, followed immediately by two consecutive trials of the non-dominant hand, are undertaken. The average time taken to complete the task, for each of the dominant and non-dominant hand, is calculated. The 9HPT has high intra- and inter-rater reliability and is the most commonly used measure of upper limb function in FA. This assessment will be administered to participants with FA only.
Measured: Baseline to 24 months
Speech analysis scores
A battery of speech evaluations will be administered and recorded on a laptop for analysis, using Redenlab software. This will include: reading of a phonetically-balanced passage, sustained vowel sound, listing days of the week, repeating syllables, and a monologue task. This will form a measure of dysarthria. Redenlab is a US-Australian speech-testing company, https://redenlab.com. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Low-Contrast Sloan Letter Chart (LCSLC) test score
Contrast letter acuity for vision will be assessed using back-lit Low-Contrast Sloan Letter Charts (LCSLCs). Participants will sit at an eye distance of 2 metres from the chart. Binocular vision will be assessed using participants' normal corrective lenses where relevant. Participants are required to read each letter on the chart. Three charts will be presented, with three different visual contrast levels: 100% (equivalent to high-contrast visual acuity), 2.5%, and 1.25%. The maximum total score across the three charts (number of letters read correctly) is 240. Scores for each individual chart will also be recorded. This assessment will be administered to participants with FA only.
Measured: Baseline to 24 months
Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale score
The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) Scale is a 10-item screening measure assessing attention and concentration, executive functioning, memory, language, visuospatial functioning, abstract thinking, and neuropsychiatric features. Each item has an associated raw score and pass/fail evaluation. The total raw score (maximum 120) and the total number of "failed" items (maximum 10) will be recorded. This scale is to be administered to participants who are aged 18 years and over. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Hayling Sentence Completion Test (HSCT) scores
The Hayling Sentence Completion Test (HSCT) is an orally-administered test measuring response initiation and response suppression. In the first section, participants are asked to complete a series of incomplete sentences with a sensible word. In the second section, participants are asked to supply an unrelated word to complete each sentence. Scaled scores for total response latency in each section, a scaled score for errors in the second section, and an overall scale score are calculated. This test is to be administered to participants who are aged 18 years and over. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Hospital Anxiety and Depression Scale (HADS) scores
The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-assessment scale designed to screen for states of depression and anxiety and measure the severity of these states. It contains a 7-item subscale for each of Anxiety (HADS-A) and Depression (HADS-D). Possible scores for each of the HADS-Anxiety and HADS-Depression scales range from 0 to 21. Higher scores indicate more severe anxiety and depression. This scale is be administered to participants who are aged 18 year and over. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Junior Hayling Sentence Completion Test (Junior HSCT) scores
The Junior Hayling Sentence Completion Test (Junior HSCT) is an orally-administered measure of response initiation and response suppression in children. To be administered to participants who are aged at least 8 years but less than 18 years. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Paediatric Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale score
The Paediatric Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale is an assessment of the executive, visual-spatial and linguistic components of cognitive control and affect in children. Currently under development. To be incorporated as a secondary outcome measure if available at the time of study commencement. To be administered to participants who are aged at least 8 years but less than 18 years. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Revised Children's Anxiety and Depression scale (RCADS) scores
The Revised Child Anxiety and Depression Scale (RCADS) is a 47-item, self-report questionnaire six subscales: separation anxiety disorder, social phobia, generalized anxiety disorder, panic disorder, obsessive compulsive disorder, and major depressive disorder. It also yields a Total Anxiety Scale and a Total Internalizing Scale. A higher score indicates a higher level of the given disorder/syndrome. This scale is to be administered to participants who are aged at least 8 years but less than 18 years. This assessment will be administered to participants with FA and controls.
Measured: Baseline to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start10 Feb 2021
- Primary completionOct 2025 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Friedreich AtaxiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monash University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota, RWTH Aachen University, University of Campinas, Brazil, Children's Hospital of Philadelphia, University of Florida, Friedreich's Ataxia Research Alliance, McGill University
- Responsible party
- Principal investigator, Nellie Georgiou-Karistianis, Monash University
- Investigators
- Nellie Georgiou-Karistianis, PhD, Principal investigator, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04349514
- Sponsor's protocol ID
- TRACK-FA
- Acronym
- (TRACK-FA)
- Status last verified
- Oct 2024
- First submitted
- 1 Apr 2020
- Last updated
- 27 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40767617Georgiou-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.
PubMed 40119735Georgiou-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.
PubMed 36410013Hernandez 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.
PubMed 34713932
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
- ClinicalTrials.gov ID
- NCT04349514
- Acronym / sponsor ID
- (TRACK-FA) / TRACK-FA
- Conditions
- Friedreich Ataxia
- Keywords
- Neuroimaging, Longitudinal, Biomarkers, Natural history
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Monash UniversityUniversity, hospital or other
- Collaborators
- University of Minnesota, RWTH Aachen University, University of Campinas, Brazil, Children's Hospital of Philadelphia, University of Florida, Friedreich's Ataxia Research Alliance, McGill University
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 16 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Friedreich ataxia (FA) is a multi-system progressive disorder with the most prevalent and prominent symptoms relating to dysfunction in the central and peripheral nervous system, including, loss of balance and coordination, frequent falls, loss of ambulation, dysarthria, dysphagia and loss of vision and hearing. Other symptoms include cardiomyopathy, diabetes, scoliosis and fatigue. Age of onset can vary but most often presents during childhood, ages 5-15 years.
There is currently no cure and no disease-modifying treatment. Drug candidates to potentially treat FA are under development; however, there is a lack of well- characterized neuroimaging biomarkers for testing their efficacy in clinical trials, hampering this process. Establishing disease-specific neuroimaging biomarkers to track disease progression requires high-quality longitudinal data from large cohorts of patients, compared to controls. In rare diseases, such as FA, this can only be achieved through multi-site collaboration.
The aim of TRACK-FA is to develop an FA neuroimaging dataset from brain and spinal cord that is suitable for assessing the potential value of neuroimaging biomarkers and providing a basis for instituting them in clinical trials. The dataset will comprise a range of neuroimaging measures to assess changes in spinal cord and brain regions that have previously shown to be compromised in individuals with FA. In addition to neuroimaging measures, TRACK-FA will also include clinical, cognitive data and biospecimen data. The TRACK-FA dataset will provide a unique opportunity for academic researchers in collaboration with industry partners to access the images, subsidiary data, and associated clinical data for community research.
This multi-centre study is a collaborative effort across six academic institutions, together with industry partners and the Friedreich's Ataxia Research Alliance USA (FARA).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Friedreich ataxia | – | Other: Natural historyIndividuals with a diagnosis of Friedreich ataxia. |
| Control | – | Other: Natural historyIndividuals without a diagnosis of Friedreich ataxia. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Natural historyLongitudinal observation of neuroimaging, clinical, and blood markers. | Other | Control, Friedreich ataxia |
Primary outcome
Baseline dentate nuclei magnetic susceptibility
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
13 secondary outcomes
Modified Friedreich Ataxia Rating Scale (mFARS) score
Time frame: Baseline to 24 months
Upright Stability (US) score
Time frame: Baseline to 24 months
Activities of Daily Living (ADL) score
Time frame: Baseline to 24 months
Scale for the Assessment and Rating of Ataxia (SARA) score
Time frame: Baseline to 24 months
9 Hole Peg Test times
Time frame: Baseline to 24 months
Speech analysis scores
Time frame: Baseline to 24 months
Low-Contrast Sloan Letter Chart (LCSLC) test score
Time frame: Baseline to 24 months
Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale score
Time frame: Baseline to 24 months
Hayling Sentence Completion Test (HSCT) scores
Time frame: Baseline to 24 months
Hospital Anxiety and Depression Scale (HADS) scores
Time frame: Baseline to 24 months
Junior Hayling Sentence Completion Test (Junior HSCT) scores
Time frame: Baseline to 24 months
Paediatric Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale score
Time frame: Baseline to 24 months
Revised Children's Anxiety and Depression scale (RCADS) scores
Time frame: Baseline to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2024.
- Derived from this study: PubMed 40767617Shiraishi 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.
- Derived from this study: PubMed 40119735Georgiou-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.
- Derived from this study: PubMed 36410013Georgiou-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.
- Derived from this study: PubMed 34713932Hernandez 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nellie Georgiou-Karistianis, PhD principal investigator
Monash University
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Friedreich Ataxia, run by Monash University at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Australia, Brazil, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline dentate nuclei magnetic susceptibility (time frame: Baseline). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04349514, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2024.