Clinical trial NCT00136630: Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
Official title: Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spinocerebellar Ataxias
Spastic Paraplegias
Keywords: dominant spinocerebellar degenerations
new rate scales
natural history
molecular biology
candidate genes
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: Assistance Publique - Hôpitaux de Paris
First posted: 2005-08-29
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: French population

Brief 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.


Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: Hôpital Neurologique Pierre Wertheimer
city: Marseille
country: France
facility: Hôpital La Timone
city: Nîmes
country: France
facility: Hôpital Carémeau
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Toulouse
country: France
facility: Hôpital Purpan
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Alexandra Dürr, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpitaux Civils de Lyon
name: Broussolle Emmanuel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpitaux de Nîmes
name: Pierre Labauge, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpitaux de Bordeaux
name: Cyril Goizet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpitaux de Toulouse
name: Patrick Calvas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Marseille
name: Jean-Philippe Azulay, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpitaux de Rouen
name: Didier Hannequin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpitaux de Grenoble
name: Pierre Pollak, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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