Spinocerebellar Ataxia Type 27B
Conditions
Keywords
ataxia, SCA27B, FGF14, Natural History Study, Outcome Validation
Brief summary
This international, multi-center, multi-modal, and prospective observational cohort study aims to validate trial outcomes for capturing disease progression in Spinocerebellar Ataxia Type 27B (SCA27B), with combined multi-modal capture of clinical outcome assessments, digital-motor assessments, and molecular biomarkers.
Detailed description
The investigators will perform an international, multi-center, multi-modal, and registry-based standardized prospective Natural History Study (NHS) in Spinocerebellar Ataxia Type 27B (SCA27B), including the presymptomatic phase of the disease (i.e. presymptomatic subjects at risk for SCA27B). Participants will be assessed annually. Clinical data, including clinician-reported outcomes and patient-focused outcomes, will be entered into a clinical database customized to the requirements of this specific study (SCA27B Registry; www.ataxia-registries.org). Digital-motor outcomes comprise digital gait assessment by wearable sensors, and digital assessment of upper limb movements by Q-Motor. At all study visits, participants will be asked to donate biosamples; and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy. Based on this multimodal protocol, the study aims to determine the most sensitive, comprehensive, and reliable outcome measures for future therapeutic trials in SCA27B.
Interventions
None listed
Sponsors
University Hospital Tuebingen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* SCA27B: genetic diagnosis of ≥250 uninterrupted GAA repeat expansions in FGF14 * SCA27B risk subject: asymptomatic first-degree relative of SCA27B participant with known or unknown carrier status * Unrelated healthy controls: no signs or history of neurological or psychiatric disease AND * Written informed consent AND * Participants are willing and able to comply with study procedures
Exclusion criteria
* SCA27B: Missing informed consent * SCA27B risk subjects: Missing informed consent * Unrelated healthy controls: Missing informed consent, or concurrent neurological, orthopedic, or other diseases interfering with the motor assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Friedreich Ataxia Rating Scale - Neurological Examination Part E (upright stability) from baseline to 2-year follow-up | 24 months | Severity of ataxia in the gait and balance domain will be assessed by application of part E of the neurological examination of Friedreich Ataxia Rating Scale (FARS-E). The total score is calculated as the sum of 7 items, yielding a total score between 0 and 28. Hereby, higher FARS-E scores indicate more severe functional impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up | 24 months | Severity of ataxia will be assessed by application of the Scale for the Assessment and Rating of Ataxia (SARA). The total score is calculated as the sum of 8 items, yielding a total score between 0 and 40. Hereby, higher SARA scores indicate more severe disease. |
| Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) from baseline to 2-year follow-up | 24 months | Impairment in activities of daily living will be assessed by application of the Activities of Daily Living part of the Friedreich Ataxia Rating Scale (FARS-ADL). The total score is calculated as the sum of 9 items, yielding a total score between 0 and 36. Hereby, higher FARS-ADL scores indicate more severe functional impairment. |
| Patient Global Impression of Change (PGI-C) from baseline to 1-year and 2-year follow-up | 24 months | Patient-experienced longitudinal change of ataxia severity will be assessed by asking for the Patient Global Impression of Change (PGI-C) as patient-reported outcome and anchor for longitudinal validation of other outcomes. The PGI-C consists of 7 levels from 1 = very much worse, to 4 = no change, to 7 = very much improved. |
| Digital gait and balance assessment from baseline to 2-year follow-up | 24 months | Gait and balance will be assessed digitally with body-worn sensors (inertial measurement units), which record acceleration or rotational movements during specific gait and balance tasks. |
Countries
Czechia, Germany, Italy, Spain
Contacts
CONTACTMatthis Synofzik, Prof. Dr.
CONTACTAndreas Traschütz, Dr. Dr.
PRINCIPAL_INVESTIGATORMatthis Synofzik, Prof. Dr.
University Hospital Tübingen
PRINCIPAL_INVESTIGATORAndreas Traschütz, Dr. Dr.
University Hospital Tübingen
Outcome results
None listed