Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias
- Conditions
- Spastic Ataxia
- Registration Number
- NCT04297891
- Lead Sponsor
- Dr. Rebecca Schule
- Brief Summary
The aim of this study is to determine the clinical spectrum and natural progression of Spastic Ataxias (SPAX) and related disorders in a prospective multicenter natural history study, identify digital, imaging and molecular biomarkers that can assist in diagnosis and therapy development and study the genetic etiology and molecular mechanisms of these diseases.
- Detailed Description
The investigators will perform a registry-based standardized prospective Natural History Study (NHS) in SPAX and related disorders. Participants will be seen annually. At study visits a standardized clinical examination will be performed including application of clinical rating scales (selection of rating scales may vary depending on the individual phenotype and specific genotype); data will be entered into a clinical database (HSP Registry; https://www.hsp-registry.net and ARCA Registry; www.ARCA-registry.org). At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy.
Optionally, additional examinations may be performed including imaging, quantitative movement analysis, neuropsychological examinations, analysis of patient or observer reported outcomes and OMICS analysis to characterize molecular biomarkers.
In participants without a genetic diagnosis, next generation sequencing may be performed.
Thus this study will establish a model of disease progression and mechanistic evolution in SPAX, which will allow to track and understand selective as well as overlapping dysfunction of the cerebellum and corticospinal tract. In a transatlantic natural history study we will longitudinally validate clinician- and patient-reported, digital and molecular outcomes. In addition, we will improve on existing and develop new outcome parameters that show superior sensitivity to change. These include a novel clinical SPAX composite score, a smartphone mHealth toolbox combining remote assessment of daily living by wearable sensors with app-based patient-entered outcomes (SPAX.app), and multimodal MRI radiomics with an innovative machine learning approach for multisite MRI analysis, including in particular the infratentorial space. Longitudinal validation of targeted fluid biomarker candidates will aslo be an important part.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
- ARSACS cohort: genetic diagnosis of ARSACS and clinically manifest disease
- SPG7 cohort: genetic diagnosis of SPG7 and clinically manifest disease
- Unrelated healthy controls: no signs or history of neurological or psychiatric disease
AND
- written informed consent provided
AND
- Participants are willing and able to comply with study procedures
- Missing informed consent
- For controls: evidence of a neurodegenerative disease or movement disorders; inability to give informed consent
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up 24 months Severity of the ataxia component of the disease 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 al items, yielding a total score between 0 and 38. Hereby, higher SARA scores indicate more severe disease.
Change of Spastic Paraplegia Rating Scale (SPRS) from baseline to 2-year follow-up 24 months Severity of the spasticity component of the disease will be assessed by application of the Spastic Paraplegia Rating Scale. The total score is calculated as the sum of al items, yielding a total score between 0 and 52. Hereby, higher SPRS scores indicate more severe disease.
- Secondary Outcome Measures
Name Time Method Change of Disease severity index - Autosomal recessive spastic ataxia of Charlevoix-Saguenay(DSI-ARSACS) from baseline to 2-year follow-up 24 months The DSI-ARSACS is a clinical rating scale consisting of 8 items reflecting the 3 main components of the disease (pyramidal, cerebellar, and neuropath systems) specifically developed to measure disease progression in ARSACs. The DSI-ARSACS total score can range from 0 to 38. Hereby, higher DSI-ARSACS scores indicate more severe disease.
Trial Locations
- Locations (9)
Montreal Neurological Institute of McGill University, Department of Neurology and Neurosurgery and Human Genetics
🇨🇦Montreal,, Quebec, Canada
Université de Sherbrooke
🇨🇦Saguenay, Quebec, Canada
Département d'information médicale (DIM); Département de Biostatistique, Santn 3emé Publique et Information Médicale (BIOSPIM)- Bâtiment Mazarie étage; Hôpitaux Universitaires Pitié Salpêtrière
🇫🇷Paris, France
Center for Neurology & Hertie-Institute for Clinical Brain Research, Dept. for Neurodegenerative Diseases
🇩🇪Tübingen, Baden-Württemberg, Germany
University Hospital Essen (AöR)
🇩🇪Essen, Germany
IRCCS Fondazione Stella Maris
🇮🇹Pisa, Italy
Radboud University Medical Center; Department of Neurology & Donders Institute for Brain, Cognition, and Behaviour
🇳🇱Nijmegen, Netherlands
Koç Univ. Hospital, KUTTAMNDAL
🇹🇷Istanbul, Turkey
Department of Clinical Neurosciences, University of Cambridge; John Van Geest Cambridge Centre for Brain Repair
🇬🇧Cambridge, United Kingdom
Montreal Neurological Institute of McGill University, Department of Neurology and Neurosurgery and Human Genetics🇨🇦Montreal,, Quebec, CanadaBernard Brais, MD, PhDPrincipal Investigator