Clinical trial NCT04349514: A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
Official title: A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Friedreich Ataxia
Keywords: Neuroimaging
Longitudinal
Biomarkers
Natural history
Lead sponsor: Monash University
Sponsor class: OTHER
Collaborators: name: University of Minnesota
name: RWTH Aachen University
name: University of Campinas, Brazil
name: Children's Hospital of Philadelphia
name: University of Florida
name: Friedreich's Ataxia Research Alliance
name: McGill University
First posted: 2020-04-16
Enrollment: 300
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_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.

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.

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).

Eligibility criteria: 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 outcomes:
measure: Baseline dentate nuclei magnetic susceptibility
timeFrame: Baseline
measure: Slope of change in dentate nuclei magnetic susceptibility
timeFrame: Baseline to 24 months
measure: Baseline dentate volume
timeFrame: Baseline
measure: Slope of change in dentate volume
timeFrame: Baseline to 24 months
measure: Baseline total cerebellar volume
timeFrame: Baseline
measure: Slope of change in total cerebellar volume
timeFrame: Baseline to 24 months
measure: Baseline superior cerebellar peduncle volume
timeFrame: Baseline
measure: Slope of change in superior cerebellar peduncle volume
timeFrame: Baseline to 24 months
measure: Baseline superior cerebellar peduncle fractional anisotropy
timeFrame: Baseline
measure: Slope of change in superior cerebellar peduncle fractional anisotropy
timeFrame: Baseline to 24 months
measure: Baseline superior cerebellar peduncle mean diffusivity
timeFrame: Baseline
measure: Slope of change in superior cerebellar peduncle mean diffusivity
timeFrame: Baseline to 24 months
measure: Baseline superior cerebellar peduncle radial diffusivity
timeFrame: Baseline
measure: Slope of change in superior cerebellar peduncle radial diffusivity
timeFrame: Baseline to 24 months
measure: Baseline superior cerebellar peduncle axial diffusivity
timeFrame: Baseline
measure: Slope of change in superior cerebellar peduncle axial diffusivity
timeFrame: Baseline to 24 months
measure: Baseline cervical spinal cord cross-sectional area
timeFrame: Baseline
measure: Slope of change in cervical spinal cord cross-sectional area
timeFrame: Baseline to 24 months
measure: Baseline cervical spinal cord fractional anisotropy
timeFrame: Baseline
measure: Slope of change in cervical spinal cord fractional anisotropy
timeFrame: Baseline to 24 months
measure: Baseline cervical spinal cord mean diffusivity
timeFrame: Baseline
measure: Slope of change in cervical spinal cord mean diffusivity
timeFrame: Baseline to 24 months
measure: Baseline cervical spinal cord radial diffusivity
timeFrame: Baseline
measure: Slope of change in cervical spinal cord radial diffusivity
timeFrame: Baseline to 24 months
measure: Baseline cervical spinal cord axial diffusivity
timeFrame: Baseline
measure: Slope of change in cervical spinal cord axial diffusivity
timeFrame: Baseline to 24 months
measure: Baseline cervical spine tNAA/mIns ratio
timeFrame: Baseline
measure: Slope of the cervical spine tNAA/mIns ratio
timeFrame: Baseline to 24 months
Secondary outcomes:
measure: Modified Friedreich Ataxia Rating Scale (mFARS) score
timeFrame: Baseline to 24 months
measure: Upright Stability (US) score
timeFrame: Baseline to 24 months
measure: Activities of Daily Living (ADL) score
timeFrame: Baseline to 24 months
measure: Scale for the Assessment and Rating of Ataxia (SARA) score
timeFrame: Baseline to 24 months
measure: 9 Hole Peg Test times
timeFrame: Baseline to 24 months
measure: Speech analysis scores
timeFrame: Baseline to 24 months
measure: Low-Contrast Sloan Letter Chart (LCSLC) test score
timeFrame: Baseline to 24 months
measure: Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale score
timeFrame: Baseline to 24 months
measure: Hayling Sentence Completion Test (HSCT) scores
timeFrame: Baseline to 24 months
measure: Hospital Anxiety and Depression Scale (HADS) scores
timeFrame: Baseline to 24 months
measure: Junior Hayling Sentence Completion Test (Junior HSCT) scores
timeFrame: Baseline to 24 months
measure: Paediatric Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) scale score
timeFrame: Baseline to 24 months
measure: Revised Children's Anxiety and Depression scale (RCADS) scores
timeFrame: Baseline to 24 months
Other outcomes:
measure: Serum neurofilament light chain (NfL) level
timeFrame: Baseline to 24 months
measure: Frataxin protein level
timeFrame: Baseline to 24 months
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Minneapolis
country: United States
facility: Center for Magnetic Resonance Research, University of Minnesota
state: Minnesota
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Clayton
country: Australia
facility: Monash Biomedical Imaging, Monash University
state: Victoria
city: São Paulo
country: Brazil
facility: Lab of Neuroimaging and Dept of Neurology, University of Campinas (UNICAMP)
city: Montréal
country: Canada
facility: McGill University
state: Quebec
city: Aachen
country: Germany
facility: Department of Neurology, RWTH Aachen University
Study officials:
affiliation: Monash University
name: Nellie Georgiou-Karistianis, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.