Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Other |
Serum neurofilament light chain (NfL) level |
Neurofilament light chain (NfL) is a peripherally-accessible blood biomarker of neuroaxonal destruction in various neurodegenerative diseases. It has been shown for several such diseases that blood NfL might serve as a progression biomarker as well as a treatment response biomarker. Blood samples will be collected at each of the three study visits, stored locally, and shipped to a central location for analysis of NfL levels. |
Baseline to 24 months |
|
Other |
Frataxin protein level |
Levels of frataxin protein in lymphocyte and serum will be measured. Frataxin is produced at reduced levels in FA as a consequence of the guanine-adenine-adenine (GAA) repeat expansion in the frataxin gene (FXN) on chromosome 9. Blood samples will be collected at each of the three study visits, stored locally, and shipped to a central location for analysis of frataxin levels. |
Baseline to 24 months |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
|
Primary |
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 |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|
Secondary |
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. |
Baseline to 24 months |
|