Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations

Spinocerebellar Ataxias Clinical Trial

Official title:

Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00136630
• Other study ID #: RBM01-59 _ AOM03059
• Status: Completed
• Start date: May 2005
• Est. completion date: May 2020

Study information

• Verified date: August 2021
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The autosomal dominant spinocerebellar degenerations are a highly heterogeneous, clinically and genetically, group of rare diseases and of severe evolution. So far, the responsible genes for less than 50% of the cases are known and because of their rarity, there are no phenotype-genotype correlations and well-defined disease history.

The aims of the project are to develop and validate quantitative tools of the cerebellar syndrome and of the spasticity, to establish links between the phenotype and the result of the molecular analysis, to identify new loci/genes responsible for these disorders, and to establish the natural history of the disease according to the genotype.

To this end, a prospective and multicentric study is proposed for recruiting and evaluating, clinically, a cohort of 225 patients; 150 of them are already followed-up in the centers involved. A DNA collection will be set up in order to search for the implication of new loci and genes. A clinico-genetic database will be set up combining data from successive clinical evaluations and those of genotyping.

This strategy will allow access to genetic counselling and molecular diagnosis (positive, presymptomatic or prenatal diagnoses), based on a rational strategy from phenotype-genotype correlations and the information concerning the relative frequency of the genes. The detailed description, with the help of new evaluation tools and of the follow-up of the natural history of the disease according to the genotype, constitutes a crucial step in the design of therapeutical trials in these orphan disorders. Furthermore, the regular follow-up by specialized centers will allow better care of the patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: May 2020
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Progressive ataxia or paraplegia,

• Familial history of the disease (patients),

• Over 18 years of age

• No presentation of neurological or osteoarticular disorders

Exclusion Criteria:

• Refusal to participate in the protocol,

• An unknown familial history,

• Presenting with an interrecurrent disorder making the evaluation of the disease (stroke, dementia) impossible

Related Conditions & MeSH terms

• Paraplegia
• Spastic Paraplegias
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Locations

Country	Name	City	State
France	Hôpital Pellegrin	Bordeaux
France	CHU de Grenoble	Grenoble
France	Hôpital Neurologique Pierre Wertheimer	Lyon
France	Hôpital La Timone	Marseille
France	Hôpital Carémeau	Nîmes
France	Hôpital Pitié-Salpêtrière	Paris
France	Hôpital Charles Nicolle	Rouen
France	Hôpital Purpan	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (11)

Depienne C, Fedirko E, Faucheux JM, Forlani S, Bricka B, Goizet C, Lesourd S, Stevanin G, Ruberg M, Durr A, Brice A. A de novo SPAST mutation leading to somatic mosaicism is associated with a later age at onset in HSP. Neurogenetics. 2007 Aug;8(3):231-3. — View Citation

Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribaï P, Feki I, Tallaksen C, Nguyen K, Stankoff B, Ruberg M, Stevanin G, Durr A, Brice A. Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. J Med Genet. 2007 Apr;44(4):281-4. Epub — View Citation

Depienne C, Tallaksen C, Lephay JY, Bricka B, Poea-Guyon S, Fontaine B, Labauge P, Brice A, Durr A. Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases. J Med Genet. 2006 Mar; — View Citation

du Montcel ST, Charles P, Ribai P, Goizet C, Le Bayon A, Labauge P, Guyant-Maréchal L, Forlani S, Jauffret C, Vandenberghe N, N'guyen K, Le Ber I, Devos D, Vincitorio CM, Manto MU, Tison F, Hannequin D, Ruberg M, Brice A, Durr A. Composite cerebellar func — View Citation

Goizet C, Boukhris A, Mundwiller E, Tallaksen C, Forlani S, Toutain A, Carriere N, Paquis V, Depienne C, Durr A, Stevanin G, Brice A. Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. Hum Mutat. 2009 Feb;30(2):E3 — View Citation

Hanein S, Dürr A, Ribai P, Forlani S, Leutenegger AL, Nelson I, Babron MC, Elleuch N, Depienne C, Charon C, Brice A, Stevanin G. A novel locus for autosomal dominant "uncomplicated" hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3. Hum Genet. — View Citation

Klebe S, Durr A, Rentschler A, Hahn-Barma V, Abele M, Bouslam N, Schöls L, Jedynak P, Forlani S, Denis E, Dussert C, Agid Y, Bauer P, Globas C, Wüllner U, Brice A, Riess O, Stevanin G. New mutations in protein kinase Cgamma associated with spinocerebellar — View Citation

Ribaï P, Depienne C, Fedirko E, Jothy AC, Viveweger C, Hahn-Barma V, Brice A, Durr A. Mental deficiency in three families with SPG4 spastic paraplegia. Eur J Hum Genet. 2008 Jan;16(1):97-104. Epub 2007 Oct 24. — View Citation

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. — View Citation

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 spinocer — View Citation

Waters MF, Minassian NA, Stevanin G, Figueroa KP, Bannister JP, Nolte D, Mock AF, Evidente VG, Fee DB, Müller U, Dürr A, Brice A, Papazian DM, Pulst SM. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervou — View Citation

* Note: There are 11 references in all — Click here to view all references

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