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SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
This study is currently recruiting participants.
Verified by Institut National de la Santé Et de la Recherche Médicale, France, October 2007
Sponsors and Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
Institut des Maladies Rares
Information provided by: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT00140829
  Purpose

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.


Condition Phase
Cerebellar Ataxias
Spastic Paraplegias
Phase I

Genetics Home Reference related topics: Friedreich ataxia spastic paraplegia type 4 Troyer syndrome
MedlinePlus related topics: Genetic Counseling
U.S. FDA Resources
Study Type: Observational
Study Design: Prospective
Official Title: Clinical and Genetic Analysis of Autosomal Recessive Forms of Cerebellar Ataxias and Spastic Paraplegias

Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Estimated Enrollment: 6000
Study Start Date: July 2003
Estimated Study Completion Date: December 2007
  Eligibility

Ages Eligible for Study:   2 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Progressive ataxia or paraplegia

Exclusion Criteria:

  • Lack of signed informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00140829

Contacts
Contact: Alexandra Dürr, MD, PhD 0033142162182 durr@ccr.jussieu.fr

Locations
Algeria
CHU Mustapha Recruiting
Algiers, Algeria, 16000
Contact: Miriem Tazir, MD, PhD     0021321235640     meriemtazir@yahoo.com    
Principal Investigator: Miriem Tazir, MD, PhD            
Denmark
The Panum Institute Recruiting
Copenhagen, Denmark, 2200
Contact: Jorgen E Nielsen, MD, PhD     004535527816     jnielsen@imbg.ku.dk    
Principal Investigator: Jorgen E Nielsen, MD, PhD            
Sub-Investigator: Kristin Husby Scheuer, MD            
France
Pitié-Salpêtrière Hospital Recruiting
Paris, France, 75013
Contact: Alexandra Dürr, MD, PhD     0033142162182     durr@ccr.jussieu.fr    
Principal Investigator: Alexandra Dürr, MD, PhD            
Sub-Investigator: Alexis Brice, MD            
Sub-Investigator: Bertrand Fontaine, MD, PhD            
CHU d'Angers Recruiting
Angers, France, 49000
Contact: Christophe Verny, MD     003241354613     chverny@chu-angers.fr    
Principal Investigator: Christophe Verny, MD            
CHU Recruiting
Grenoble, France, 38000
Contact: Pierre Pollak, MD, PhD     0033476765791     pierre.pollak@ujf-grenoble.fr    
Hôpital Armand Trousseau Recruiting
Paris, France, 75012
Contact: Diana Rodriguez, MD         diana.rodriguez@trs.ap-hop-paris.fr    
Principal Investigator: Diana Rodriguez, MD            
Hôpital de la Timone Recruiting
Marseille, France, 13000
Contact: Jean-Philippe Azulay, MD, PhD     0033491386579     jean-philippe.azulay@mail.ap-hm.fr    
Principal Investigator: Jean-Philippe Azulay, MD, PhD            
Hôpital Carémeau Recruiting
Nîmes, France, 30000
Contact: Pierre Labauge, MD, PhD     0033466683263     labauge@hotmail.com    
Principal Investigator: Pierre Labauge, MD, PhD            
Hôpital Charles Nicolle Recruiting
Rouen, France, 76000
Contact: Didier Hannequin, MD, PhD     0033232888170     Didier.hannequin@chu-rouen.fr    
Principal Investigator: Didier Hannequin, MD, PhD            
Hôpitaux de Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63000
Contact: Odile Boespflug-Tanguy, MD, PhD     0033473448657     Odile.BOESPFLUG@inserm.u-clermont1.fr    
Principal Investigator: Odile Boespflug-Tanguy, MD, PhD            
Italy
Dipartimento Di Scienze Neurologiche Recruiting
Napoli, Italy, 80131
Contact: Alessandro Filla, MD, PhD     00390817462476     afilla@unina.it    
Principal Investigator: Alessandro Filla, MD, PhD            
Molecular Medicine and Department of Neurosciences Recruiting
Roma, Italy, 00165
Contact: Enrico Bertini, MD, PhD     00390668592105     ebertini@tin.it    
Principal Investigator: Enrico Bertini, MD, PhD            
Lebanon
Université Saint-Joseph Recruiting
Beirut, Lebanon, 1107 2180
Contact: André Mégarbané, MD, PhD     009611614046     megarban@dm.net.lb    
Principal Investigator: André Mégarbané, MD, PhD            
Morocco
CHU de Rabat Recruiting
Rabat, Morocco
Contact: Ali Benomar, MD, PhD         ali.benomar@hotmail.com    
Principal Investigator: Ali Benomar, MD, PhD            
Portugal
Hospital San Sebastião Recruiting
Santa Maria de Feira, Portugal, 4520-211
Contact: Paula Coutinho, MD, PhD     00351256362847     pcoutinho@hospitalfeira.min-saude.pt    
Principal Investigator: Paula Coutinho, MD, PhD            
Saudi Arabia
King Khalid University Hospital Recruiting
Riyadh, Saudi Arabia, 11461
Contact: Mustapha AM Dalih, MD         mustapha@ksu.edu.sa    
Principal Investigator: Mustapha AM Salih, MD            
United Kingdom
The National Hospital Recruiting
London, United Kingdom, WC1N 3BG
Contact: Nicholas W Wood, MD, PhD     00442078373611     nwood@ion.ucl.ac.uk    
Principal Investigator: Nicholas W Wood, MD, PhD            
Royal Free and University College Medical School Recruiting
London, United Kingdom, NW3 2PF
Contact: Thomas T Warner, MD, PhD         TWarner@rfc.ucl.ac.uk    
Principal Investigator: Thomas T Warner, MD, PhD            
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Institut des Maladies Rares
Investigators
Principal Investigator: Alexandra Dürr, MD, PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: Alessandro Filla, MD, PhD Federico II University
Principal Investigator: André Mégarbané, MD Université Saint-Joseph
Principal Investigator: Ali Benomar, MD, PhD CHU de Rabat
Principal Investigator: Christophe Verny, MD CHU d'Angers
Principal Investigator: Didier Hannequin, MD, PhD Hôpitaux de Rouen
Principal Investigator: Diana Rodriguez, MD Assistance Publique - Hôpitaux de Paris
Principal Investigator: Enrico Bertini, MD Università de Roma
Principal Investigator: François Tison, MD, PhD Hôpitaux de Bordeaux
Principal Investigator: Jorgen E Nielsen, MD, PhD The Panum Institute
Principal Investigator: Mustapha Salih, MD College of Medicine and KKUH
Principal Investigator: Miriem Tazir, MD, PhD Université d'Alger
Principal Investigator: Nicholas W Wood, MD, PhD Institute of Neurology
Principal Investigator: Odile Boespflug-Tanguy, MD, PhD Hôpitaux de Clermont-Ferrand
Principal Investigator: Jean-Philippe Azulay, MD, PhD Assistance Publique - Hôpitaux de Marseille
Principal Investigator: Paula Coutinho, MD, PhD University of Porto
Principal Investigator: Pierre Labauge, MD, PhD Hôpitaux de Nîmes
Principal Investigator: Pierre Pollak, MD, PhD Hôpitaux de Grenoble
Principal Investigator: Thomas T Warner, MD, PhD University College, London
  More Information

Related Info  This link exits the ClinicalTrials.gov site

Publications of Results:
Moreira MC, Klur S, Watanabe M, Nemeth AH, Le Ber I, Moniz JC, Tranchant C, Aubourg P, Tazir M, Schols L, Pandolfo M, Schulz JB, Pouget J, Calvas P, Shizuka-Ikeda M, Shoji M, Tanaka M, Izatt L, Shaw CE, M'Zahem A, Dunne E, Bomont P, Benhassine T, Bouslam N, Stevanin G, Brice A, Guimaraes J, Mendonca P, Barbot C, Coutinho P, Sequeiros J, Durr A, Warter JM, Koenig M. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet. 2004 Mar;36(3):225-7. Epub 2004 Feb 8.
Le Ber I, Bouslam N, Rivaud-Pechoux S, Guimaraes J, Benomar A, Chamayou C, Goizet C, Moreira MC, Klur S, Yahyaoui M, Agid Y, Koenig M, Stevanin G, Brice A, Durr A. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain. 2004 Apr;127(Pt 4):759-67. Epub 2004 Jan 21.
Le Ber I, Moreira MC, Rivaud-Pechoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Said G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Durr A. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003 Dec;126(Pt 12):2761-72. Epub 2003 Sep 23.
Le Ber I, Camuzat A, Castelnovo G, Azulay JP, Genton P, Gastaut JL, Broglin D, Labauge P, Brice A, Durr A. Prevalence of dentatorubral-pallidoluysian atrophy in a large series of white patients with cerebellar ataxia. Arch Neurol. 2003 Aug;60(8):1097-9.
Bouslam N, Benomar A, Azzedine H, Bouhouche A, Namekawa M, Klebe S, Charon C, Durr A, Ruberg M, Brice A, Yahyaoui M, Stevanin G. Mapping of a new form of pure autosomal recessive spastic paraplegia (SPG28). Ann Neurol. 2005 Apr;57(4):567-71.
Durr A, Camuzat A, Colin E, Tallaksen C, Hannequin D, Coutinho P, Fontaine B, Rossi A, Gil R, Rousselle C, Ruberg M, Stevanin G, Brice A. Atlastin1 mutations are frequent in young-onset autosomal dominant spastic paraplegia. Arch Neurol. 2004 Dec;61(12):1867-72.
Stevanin G, Durr A, Dussert C, Penet C, Brice A. Mutations in the FGF14 gene are not a major cause of spinocerebellar ataxia in Caucasians. Neurology. 2004 Sep 14;63(5):936. No abstract available.
Stevanin G, Hahn V, Lohmann E, Bouslam N, Gouttard M, Soumphonphakdy C, Welter ML, Ollagnon-Roman E, Lemainque A, Ruberg M, Brice A, Durr A. Mutation in the catalytic domain of protein kinase C gamma and extension of the phenotype associated with spinocerebellar ataxia type 14. Arch Neurol. 2004 Aug;61(8):1242-8.
Stevanin G, Bouslam N, Thobois S, Azzedine H, Ravaux L, Boland A, Schalling M, Broussolle E, Durr A, Brice A. Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. Ann Neurol. 2004 Jan;55(1):97-104.
Tallaksen CM, Guichart-Gomez E, Verpillat P, Hahn-Barma V, Ruberg M, Fontaine B, Brice A, Dubois B, Durr A. Subtle cognitive impairment but no dementia in patients with spastin mutations. Arch Neurol. 2003 Aug;60(8):1113-8.
Fernet M, Gribaa M, Salih MA, Seidahmed MZ, Hall J, Koenig M. Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder. Hum Mol Genet. 2005 Jan 15;14(2):307-18. Epub 2004 Dec 1.
Stevanin G, Durr A, Benammar N, Brice A. Spinocerebellar ataxia with mental retardation (SCA13). Cerebellum. 2005;4(1):43-6. Review.
Stevanin G, Broussolle E, Streichenberger N, Kopp N, Brice A, Durr A. Spinocerebellar ataxia with sensory neuropathy (SCA25). Cerebellum. 2005;4(1):58-61.
Klebe S, Durr A, Rentschler A, Hahn-Barma V, Abele M, Bouslam N, Schols L, Jedynak P, Forlani S, Denis E, Dussert C, Agid Y, Bauer P, Globas C, Wullner U, Brice A, Riess O, Stevanin G. New mutations in protein kinase Cgamma associated with spinocerebellar ataxia type 14. Ann Neurol. 2005 Nov;58(5):720-9.
Latouche M, Fragner P, Martin E, El Hachimi KH, Zander C, Sittler A, Ruberg M, Brice A, Stevanin G. Polyglutamine and polyalanine expansions in ataxin7 result in different types of aggregation and levels of toxicity. Mol Cell Neurosci. 2005 Nov 29; [Epub ahead of print]
Namekawa M, Ribai P, Nelson I, Forlani S, Fellmann F, Goizet C, Depienne C, Stevanin G, Ruberg M, Durr A, Brice A. SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. Neurology. 2006 Jan 10;66(1):112-4.
van de Warrenburg BP, Hendriks H, Durr A, van Zuijlen MC, Stevanin G, Camuzat A, Sinke RJ, Brice A, Kremer BP. Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort. Ann Neurol. 2005 Apr;57(4):505-12.
Biancalana V, Toft M, Le Ber I, Tison F, Scherrer E, Thibodeau S, Mandel JL, Brice A, Farrer MJ, Durr A. FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. Arch Neurol. 2005 Jun;62(6):962-6.
Elleuch N, Depienne C, Benomar A, Hernandez AM, Ferrer X, Fontaine B, Grid D, Tallaksen CM, Zemmouri R, Stevanin G, Durr A, Brice A. Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia. Neurology. 2006 Mar 14;66(5):654-9.
Namekawa M, Nelson I, Ribai P, Durr A, Denis E, Stevanin G, Ruberg M, Brice A. A founder effect and mutational hot spots may contribute to the most frequent mutations in the SPG3A gene. Neurogenetics. 2006 May;7(2):131-2. Epub 2006 Apr 13. No abstract available.
Lossos A, Stevanin G, Meiner V, Argov Z, Bouslam N, Newman JP, Gomori JM, Klebe S, Lerer I, Elleuch N, Silverstein S, Durr A, Abramsky O, Ben-Nariah Z, Brice A. Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity. Arch Neurol. 2006 May;63(5):756-60.
Klebe S, Azzedine H, Durr A, Bastien P, Bouslam N, Elleuch N, Forlani S, Charon C, Koenig M, Melki J, Brice A, Stevanin G. Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3. Brain. 2006 Jan 24; [Epub ahead of print]
Ribai P, Stevanin G, Bouslam N, Pontier B, Nelson I, Fontaine B, Dussert C, Charon C, Durr A, Brice A. A new phenotype linked to SPG27 and refinement of the critical region on chromosome. J Neurol. 2006 Jun;253(6):714-719. Epub 2006 Mar 6.
Le Ber I, Clot F, Vercueil L, Camuzat A, Viemont M, Benamar N, De Liege P, Ouvrard-Hernandez AM, Pollak P, Stevanin G, Brice A, Durr A. Predominant dystonia with marked cerebellar atrophy: a rare phenotype in familial dystonia. Neurology. 2006 Nov 28;67(10):1769-73.
Stevanin G, Montagna G, Azzedine H, Valente EM, Durr A, Scarano V, Bouslam N, Cassandrini D, Denora PS, Criscuolo C, Belarbi S, Orlacchio A, Jonveaux P, Silvestri G, Hernandez AM, De Michele G, Tazir M, Mariotti C, Brockmann K, Malandrini A, van der Knapp MS, Neri M, Tonekaboni H, Melone MA, Tessa A, Dotti MT, Tosetti M, Pauri F, Federico A, Casali C, Cruz VT, Loureiro JL, Zara F, Forlani S, Bertini E, Coutinho P, Filla A, Brice A, Santorelli FM. Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity. Neurogenetics. 2006 May 13; [Epub ahead of print]
Klebe S, Lacour A, Durr A, Stojkovic T, Depienne C, Forlani S, Poea-Guyon S, Vuillaume I, Sablonniere B, Vermersch P, Brice A, Stevanin G. NIPA1 (SPG6) mutations are a rare cause of autosomal dominant spastic paraplegia in Europe. Neurogenetics. 2007 Apr;8(2):155-7. Epub 2007 Jan 5. No abstract available.
Bouslam N, Bouhouche A, Benomar A, Hanein S, Klebe S, Azzedine H, Di Giandomenico S, Boland-Auge A, Santorelli FM, Durr A, Brice A, Yahyaoui M, Stevanin G. A novel locus for autosomal recessive spastic ataxia on chromosome 17p. Hum Genet. 2007 May;121(3-4):413-20. Epub 2007 Feb 2.
Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS, Martin E, Ouvrard-Hernandez AM, Tessa A, Bouslam N, Lossos A, Charles P, Loureiro JL, Elleuch N, Confavreux C, Cruz VT, Ruberg M, Leguern E, Grid D, Tazir M, Fontaine B, Filla A, Bertini E, Durr A, Brice A. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. 2007 Mar;39(3):366-72. Epub 2007 Feb 18.
Latouche M, Lasbleiz C, Martin E, Monnier V, Debeir T, Mouatt-Prigent A, Muriel MP, Morel L, Ruberg M, Brice A, Stevanin G, Tricoire H. A conditional pan-neuronal Drosophila model of spinocerebellar ataxia 7 with a reversible adult phenotype suitable for identifying modifier genes. J Neurosci. 2007 Mar 7;27(10):2483-92.
Klebe S, Durr A, Bouslam N, Grid D, Paternotte C, Depienne C, Hanein S, Bouhouche A, Elleuch N, Azzedine H, Poea-Guyon S, Forlani S, Denis E, Charon C, Hazan J, Brice A, Stevanin G. Spastic paraplegia 5: Locus refinement, candidate gene analysis and clinical description. Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 5;144(7):854-61.
Stevanin G, Paternotte C, Coutinho P, Klebe S, Elleuch N, Loureiro JL, Denis E, Cruz VT, Durr A, Prud'homme JF, Weissenbach J, Brice A, Hazan J. A new locus for autosomal recessive spastic paraplegia (SPG32) on chromosome 14q12-q21. Neurology. 2007 May 22;68(21):1837-40.

Study ID Numbers: A02191DS
Study First Received: August 25, 2005
Last Updated: October 16, 2007
ClinicalTrials.gov Identifier: NCT00140829  
Health Authority: France: Ministry of Health

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Cerebellar ataxias
Spastic paraplegias
Mutations spectrum
Linkage studies
Genetic counselling

Study placed in the following topic categories:
Paraplegia
Central Nervous System Diseases
Brain Diseases
Dyskinesias
Paralysis
Cerebellar Ataxia
Signs and Symptoms
Muscle Spasticity
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Ataxia
Neurologic Manifestations
Cerebellar Diseases
Cerebellar ataxia

Additional relevant MeSH terms:
Neuromuscular Manifestations
Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009