Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00159198
• Other study ID #: CRC01107
• Secondary ID: P011023
• Status: Terminated
• Phase: Phase 1
• First received: September 7, 2005
• Last updated: September 5, 2008
• Start date: September 2002
• Est. completion date: June 2007

Study information

• Verified date: September 2008
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

Amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD) is a rare clinical entity, in which both disorders are variably associated in the same patient or within the family. This adult-onset disorder, which is rapidly fatal, occurs in some families with autosomal dominant (AD) transmission and age-dependant penetrance. Two studies have provided evidence for linkage of this condition to chromosomes 15 (in a single family) and 9 (in five families). However, none of these loci have been yet confirmed. Through a national network of 10 centres with specialists for FTD and/or ALS, we have identified 35 probands with ALS-FTD, including 13 with a family history consistent with AD inheritance.

Mutations in the SOD1 and tau genes, respectively responsible for autosomal dominant forms of ALS and FTD, will be excluded by direct sequencing. We will then extend the pedigree of the 13 autosomal dominant families to all consenting first, second and eventually third degree relatives, using well defined criteria for FTD and ALS. The same strategy will be applied to newly identified families during the course of the project (at least, seven families with AD inheritance expected). Linkage studies will be performed in the 20 families using markers from the two candidate regions on chromosomes 9 and 15. Then, refinement of the candidate region will be obtained by analyzing the linked families with a high density of microsatellite markers. This should lead to the refinement of the candidate regions, allowing to search for mutations in candidate genes. Genes located within the critical regions will be prioritized for their analysis by sequencing, according to their expression in the nervous system and to their function.

Once the responsible gene(s) will be identified, it will then possible to define its spectrum of mutations and to establish genotype/phenotype correlations. Alternatively, if none of the candidate regions is confirmed, a genome wide search will be performed, allowing to identify one or more loci for ALS-FTD. The same strategy would then be applied to identify the corresponding gene(s). This project should contribute for identifying the molecular basis of this devastating disorder with practical consequences for genetic counselling in ALS-FTD families, and with the perspective of elucidating the pathophysiology of this disorder.

Description:

The objective of this study without direct individual benefit is to confirm the linkage with one or another region of the two identified regions (chromosomes 9 and 15) or to identify a new implicated chromosomal region, and then to reduce the linkage interval in order to identify the responsible gene(s) and characterize the mutations with the study of at least 9 families with FTD and ALS.

Other known NCT identifiers

• NCT00140777

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 400
• Est. completion date: June 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• ALS with FTD, "pure" FTD but with knowledge of relatives with ALS-FTD or "pure" ALS, "pure" ALS but with knowledge of relatives with ALS-FTD or "pure" FTD (not carriers of a mutation in the tau and SOD1 genes), relatives signing the informed consent

Exclusion Criteria:

• Minors, persons refusing to sign the informed consent

Study Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Aphasia, Primary Progressive
• Dementia
• Frontotemporal Dementia
• Motor Neuron Disease
• Pick Disease of the Brain
• Sclerosis

Locations

Country	Name	City	State
France	CHU de la Côte de Nacre	Caen
France	Centre Hospitalier Universitaire de Lille	Lille
France	Hôpital La Timone	Marseille
France	Hôpital Sainte-Marguerite	Marseille
France	Hôpital Guillaume et René Laënnec	Nantes
France	Hôpital de l'Archet	Nice
France	Hôpital Pitié-Salpêtrière	Paris
France	Hôpital Pitié-Salpêtrière - Centre du Langage-Neuropsychologie	Paris
France	Hôpital Pitié-Salpêtrière - Fédération de Neurologie	Paris
France	Hôpital Pontchaillou	Rennes
France	Hôpital Charles Nicolle	Rouen
France	Centre Hospitalier	Saint-Brieuc
France	Hôpital Bellevue	Saint-Etienne
France	Hôpital Civil	Strasbourg
France	Hôpital Purpan	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Guedj E, Le Ber I, Lacomblez L, Dubois B, Verpillat P, Didic M, Salachas F, Vera P, Hannequin D, Lotterie JA, Puel M, Decousus M, Thomas-Antérion C, Magne C, Vercelletto M, Bernard AM, Golfier V, Pasquier J, Michel BF, Namer I, Sellal F, Bochet J, Volteau — View Citation

Le Ber I, Camuzat A, Hannequin D, Pasquier F, Guedj E, Rovelet-Lecrux A, Hahn-Barma V, van der Zee J, Clot F, Bakchine S, Puel M, Ghanim M, Lacomblez L, Mikol J, Deramecourt V, Lejeune P, de la Sayette V, Belliard S, Vercelletto M, Meyrignac C, Van Broeck — View Citation

Le Ber I, Guedj E, Gabelle A, Verpillat P, Volteau M, Thomas-Anterion C, Decousus M, Hannequin D, Véra P, Lacomblez L, Camuzat A, Didic M, Puel M, Lotterie JA, Golfier V, Bernard AM, Vercelletto M, Magne C, Sellal F, Namer I, Michel BF, Pasquier J, Salach — View Citation

Le Ber I, van der Zee J, Hannequin D, Gijselinck I, Campion D, Puel M, Laquerrière A, De Pooter T, Camuzat A, Van den Broeck M, Dubois B, Sellal F, Lacomblez L, Vercelletto M, Thomas-Antérion C, Michel BF, Golfier V, Didic M, Salachas F, Duyckaerts C, Cru — View Citation

van der Zee J, Le Ber I, Maurer-Stroh S, Engelborghs S, Gijselinck I, Camuzat A, Brouwers N, Vandenberghe R, Sleegers K, Hannequin D, Dermaut B, Schymkowitz J, Campion D, Santens P, Martin JJ, Lacomblez L, De Pooter T, Peeters K, Mattheijssens M, Vercelle — View Citation

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