SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias

Completed

• Conditions: Cerebellar Ataxias; Spastic Paraplegias

• Registration Number: NCT00140829
• Lead Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Brief Summary

Cerebellar ataxias (CA) and spastic paraplegias (SP) are genetically and clinically very heterogeneous. More than 40 loci are already known but the number of phenotypes is even greater suggesting further genetic heterogeneity. These progressive disorders are often severe and fatal, due to the absence of specific therapy. The SPATAX network combines the experience of European clinicians and scientists working on these groups of diseases. Over the past year, they have assembled the largest collection of families and achieved a number of tasks (initiation of a clinical and genetic database, distribution of DNA to participating laboratories, mapping of three new loci, and refinement of several loci). In addition to clinicians from Europe and Mediterranean countries, who play a major role in collecting families according to evaluation tools developed and validated by the SPATAX members, the group includes major European laboratories devoted to the elucidation of the molecular basis of these disorders. Each laboratory will centralize all families with a subtype of autosomal recessive (AR) CA (n=116) or SP (n=207) in order to efficiently map and identify the responsible gene(s). Genome-wide scans are already underway in 61 families. Given the expertise of the participants, the researchers expect to map and identify several genes during the course of this project. The spectrum of mutations and phenotype/genotype correlations will be analysed thanks to this unique series of patients with various phenotypes. The knowledge gained will be immediately applicable to patients in terms of improved positive diagnosis, follow-up and appropriate genetic counselling. In the long term, models for genetic entity will be developed in order to understand the pathophysiology and to identify new targets for treatment. The series of patients assembled and the precise knowledge of natural history will facilitate the implantation of therapeutic trials based on rational approaches.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-02-10
• Study First Submitted: 2005-08-25
• Study First Submitted QC: 2005-08-30
• Study First Posted: 2005-09-01
• Primary Completion: 2020-12
• Study Completion: 2020-12-30
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6000

Inclusion Criteria

• Progressive ataxia or paraplegia

Exclusion Criteria

• Lack of signed informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Characterize clinically the different forms of these diseases	Year 1 to Year 7	Validation of a new quantitative tool with more sensitive grading scale of cerebellar syndrome, spasticity and their consequences. In one single device, three tests were assessed for hand coordination ( " tapping test ", " peg board test" and " click test "), one test for dysarthria and a final test to quantify walking disorders due to spasticity (distance covered in 5 seconds).
Elucidate the molecular bases of these diseases	through study duration (through study duration (up to 14 years) )	To elucidate the molecular bases of these diseases (identify the loci/genes involved as well as those that modulate their expression) in order to enable the development of molecular diagnostics, the study of disease mechanisms, the identification of biomarkers and, subsequently, to propose new treatments.
Establish the natural history of spino-cerebellar degeneration	Year 1 to Year 7	Investigators intended to follow the clinical status of this cohort of patients for 7 years, by assessing the progression of the pathology each year with a neurological exam

Trial Locations

Locations (27)

CHU Mustapha; 🇩🇿 Algiers, Algeria

Dipartimento Di Scienze Neurologiche; 🇮🇹 Napoli, Italy

Molecular Medicine and Department of Neurosciences; 🇮🇹 Roma, Italy

Université Saint-Joseph; 🇱🇧 Beirut, Lebanon

CHU de Rabat; 🇲🇦 Rabat, Morocco

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands

Ullevål University Hospital; 🇳🇴 Oslo, Norway

University of Porto; 🇵🇹 Porto, Portugal

Hospital San Sebastião; 🇵🇹 Santa Maria Da Feira, Portugal

Université Libre de Bruxelles - Hôpital Erasme; 🇧🇪 Brussels, Belgium

The Panum Institute; 🇩🇰 Copenhagen, Denmark

CHU d'Angers; 🇫🇷 Angers, France

Hôpital Pellegrin; 🇫🇷 Bordeaux, France

Hôpitaux de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

CHU; 🇫🇷 Grenoble, France

Hôpital de la Timone; 🇫🇷 Marseille, France

Hôpital Carémeau; 🇫🇷 Nîmes, France

Hôpital Armand Trousseau; 🇫🇷 Paris, France

Pitié-Salpêtrière Hospital; 🇫🇷 Paris, France

Hôpital Charles Nicolle; 🇫🇷 Rouen, France

Hôpital Purpan; 🇫🇷 Toulouse, France

Hadassah-Hebrew University Hospital; 🇮🇱 Jerusalem, Israel

King Khalid University Hospital; 🇸🇦 Riyadh, Saudi Arabia

Clinical Centre of Serbia; 🇷🇸 Belgrade, Serbia

Hôpital Habib Bourguiba; 🇹🇳 Sfax, Tunisia

Royal Free and University College Medical School; 🇬🇧 London, United Kingdom

The National Hospital; 🇬🇧 London, United Kingdom