We perform a prospective multisite rater-trained prospective 2-year natural history study with the clinical rating scales Scale for the Assessment and rating of Ataxia (SARA) and Spastic Paraplegia Rating Scale (SPRS), both established and validated by members of this consortium, as primary outcomes.
A new SPAX composite scale – which might best capture the combined cerebellar and CST dysfunction – will be generated post hoc by combining the SPRS and SARA items that yield the highest performance in capturing disease progression.
Clinician reported outcomes (ClinRO) are complemented by PRO, digital performance measures, and molecular biomarkers, thus covering the key spectrum outcome assessments proposed by the International Rare Diseases Research Consortium (IRDiRC).
Patients with clinically manifest genetically confirmed ARSACS or SPG7 from age 6 years onwards as well as healthy controls are assessed three times over a two-year period at annual intervals.
In addition, long term collaborators (e.g. TreatHSP consortium, European Pediatric Neurology Society (EPNS)), adhering to the same rigorous quality standards defined in PROSPAX, contribute patients and controls.
Following a stringent path to trial-readiness, outcome parameters were chosen based on their suitability to be applied in a multicentric setting and for repeated application.
Outcomes that are longitudinally evaluated in addition to and cross-validated with the clinical SARA and SPRS scales include:
- ARSACS DSI, a clinical rating scale developed by Cynthia Gagnon (Saguenay)
- Patient-reported outcomes: PROMIS toolbox & in parallel development of a SPAX-specific scale by a patient-partner approach
- Digital performance outcomes: Sensor-based quantitative assessment of motor deficits by Q-motor (collaboration with Ralf Reilmann) and of gait and stance by mobile body-worn APDM Opal sensors. As a patho-anatomical digital outcome, optical coherence tomography (OCT) that has been demonstrated to show changes in retinal nerve fibre thickness specific to ARSACS and SPG7 are applied
- Brain imaging outcome parameters: map the brain microstructures underlying SPG7 and ARSACS disease progression for SPAX trials by automated MRI volumetry
- Molecular biomarkers: NfL will be quantified longitudinally in serum as a marker of axonal degeneration