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Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00159198
Recruitment Status : Terminated (Completed)
First Posted : September 12, 2005
Last Update Posted : September 8, 2008
Information provided by:
Assistance Publique - Hôpitaux de Paris

Brief 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.

Condition or disease
Frontotemporal Dementia Amyotrophic Lateral Sclerosis

Detailed 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.

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Study Type : Observational
Actual Enrollment : 400 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Study Start Date : September 2002
Actual Study Completion Date : June 2007

Patients with frontotemporal dementia and amyotrophic lateral sclerosis
Relatives (first and second degree) of patients presenting an association of frontotemporal dementia with amyotrophic lateral sclerosis

Biospecimen Retention:   Samples With DNA
Whole blood

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients and relatives coming in outcome clinics. They are all volunteers and agree to give a blood sample and signing an informed consent explaining the study.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00159198

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CHU de la Côte de Nacre
Caen, France, 14000
Centre Hospitalier Universitaire de Lille
Lille, France, 59000
Hôpital La Timone
Marseille, France, 13005
Hôpital Sainte-Marguerite
Marseille, France, 13009
Hôpital Guillaume et René Laënnec
Nantes, France, 44000
Hôpital de l'Archet
Nice, France, 06000
Hôpital Pitié-Salpêtrière - Centre du Langage-Neuropsychologie
Paris, France, 75013
Hôpital Pitié-Salpêtrière - Fédération de Neurologie
Paris, France, 75013
Hôpital Pitié-Salpêtrière
Paris, France, 75013
Hôpital Pontchaillou
Rennes, France, 35000
Hôpital Charles Nicolle
Rouen, France, 76000
Centre Hospitalier
Saint-Brieuc, France, 22000
Hôpital Bellevue
Saint-Etienne, France, 42000
Hôpital Civil
Strasbourg, France, 67000
Hôpital Purpan
Toulouse, France, 31000
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Alexis Brice, MD Assistance Publique - Hôpitaux de Paris, University Paris 6
Additional Information:
Publications of Results:

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Responsible Party: Isabelle BRINDEL, Department Clinical Research of Developpement Identifier: NCT00159198    
Obsolete Identifiers: NCT00140777
Other Study ID Numbers: CRC01107
First Posted: September 12, 2005    Key Record Dates
Last Update Posted: September 8, 2008
Last Verified: September 2008
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Amyotrophic lateral sclerosis
Frontotemporal dementia
Mutations spectrum
Linkage studies
Genetic epidemiology
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Neuromuscular Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Frontotemporal Lobar Degeneration
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations