Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

This study has been terminated.
(Completed)
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00159198
First received: September 7, 2005
Last updated: September 5, 2008
Last verified: September 2008
  Purpose

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 Phase
Frontotemporal Dementia
Amyotrophic Lateral Sclerosis
Phase 1

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Biospecimen Retention:   Samples With DNA

Whole blood


Enrollment: 400
Study Start Date: September 2002
Study Completion Date: June 2007
Groups/Cohorts
1
Patients with frontotemporal dementia and amyotrophic lateral sclerosis
2
Relatives (first and second degree) of patients presenting an association of frontotemporal dementia with 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00159198

Locations
France
CHU de la Côte de Nacre
Caen, France, 14000
Centre Hospitalier Universitaire de Lille
Lille, France, 59000
Hôpital Sainte-Marguerite
Marseille, France, 13009
Hôpital La Timone
Marseille, France, 13005
Hôpital Guillaume et René Laënnec
Nantes, France, 44000
Hôpital de l'Archet
Nice, France, 06000
Hôpital Pitié-Salpêtrière
Paris, France, 75013
Hôpital Pitié-Salpêtrière - Centre du Langage-Neuropsychologie
Paris, France, 75013
Hôpital Pitié-Salpêtrière - Fédération de Neurologie
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
Investigators
Principal Investigator: Alexis Brice, MD Assistance Publique - Hôpitaux de Paris, University Paris 6
  More Information

Additional Information:
Publications:

Responsible Party: Isabelle BRINDEL, Department Clinical Research of Developpement
ClinicalTrials.gov Identifier: NCT00159198     History of Changes
Obsolete Identifiers: NCT00140777
Other Study ID Numbers: CRC01107, P011023
Study First Received: September 7, 2005
Last Updated: September 5, 2008
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Amyotrophic lateral sclerosis
Frontotemporal dementia
Mutations spectrum
Linkage studies
Genetic epidemiology

Additional relevant MeSH terms:
Frontotemporal Dementia
Pick Disease of the Brain
Amyotrophic Lateral Sclerosis
Aphasia, Primary Progressive
Dementia
Motor Neuron Disease
Sclerosis
Aphasia
Brain Diseases
Central Nervous System Diseases
Communication Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Frontotemporal Lobar Degeneration
Language Disorders
Mental Disorders
Metabolic Diseases
Nervous System Diseases
Neurobehavioral Manifestations
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Signs and Symptoms
Speech Disorders
Spinal Cord Diseases
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on October 22, 2014