NCT00159198

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Sep 2002

Longer than P75 for all trials

Geographic Reach
1 country

15 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2002

Completed
3 years until next milestone

First Submitted

Initial submission to the registry

September 7, 2005

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 12, 2005

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2007

Completed
Last Updated

September 8, 2008

Status Verified

September 1, 2008

First QC Date

September 7, 2005

Last Update Submit

September 5, 2008

Conditions

Frontotemporal DementiaAmyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosisFrontotemporal dementiaMutations spectrumLinkage studiesGenetic epidemiology

Study Arms (2)

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

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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.

You may qualify if:

  • 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

You may not qualify if:

  • Minors, persons refusing to sign the informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

CHU de la Côte de Nacre

Caen, 14000, France

Location

Centre Hospitalier Universitaire de Lille

Lille, 59000, France

Location

Hôpital La Timone

Marseille, 13005, France

Location

Hôpital Sainte-Marguerite

Marseille, 13009, France

Location

Hôpital Guillaume et René Laënnec

Nantes, 44000, France

Location

Hôpital de l'Archet

Nice, 06000, France

Location

Hôpital Pitié-Salpêtrière - Centre du Langage-Neuropsychologie

Paris, 75013, France

Location

Hôpital Pitié-Salpêtrière - Fédération de Neurologie

Paris, 75013, France

Location

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Hôpital Pontchaillou

Rennes, 35000, France

Location

Hôpital Charles Nicolle

Rouen, 76000, France

Location

Centre Hospitalier

Saint-Brieuc, 22000, France

Location

Hôpital Bellevue

Saint-Etienne, 42000, France

Location

Hôpital Civil

Strasbourg, 67000, France

Location

Hôpital Purpan

Toulouse, 31000, France

Location

Related Publications (5)

  • Le Ber I, Guedj E, Gabelle A, Verpillat P, Volteau M, Thomas-Anterion C, Decousus M, Hannequin D, Vera 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, Salachas F, Bochet J; French research network on FTD/FTD-MND; Brice A, Habert MO, Dubois B. Demographic, neurological and behavioural characteristics and brain perfusion SPECT in frontal variant of frontotemporal dementia. Brain. 2006 Nov;129(Pt 11):3051-65. doi: 10.1093/brain/awl288.

    PMID: 17071924RESULT

  • 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, Vercelletto M, Van den Broeck M, Cruts M, De Deyn PP, Rousseau F, Brice A, Van Broeckhoven C. Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum Mutat. 2007 Apr;28(4):416. doi: 10.1002/humu.9484.

    PMID: 17345602RESULT

  • Le Ber I, van der Zee J, Hannequin D, Gijselinck I, Campion D, Puel M, Laquerriere A, De Pooter T, Camuzat A, Van den Broeck M, Dubois B, Sellal F, Lacomblez L, Vercelletto M, Thomas-Anterion C, Michel BF, Golfier V, Didic M, Salachas F, Duyckaerts C, Cruts M, Verpillat P, Van Broeckhoven C, Brice A; French Research Network on FTD/FTD-MND. Progranulin null mutations in both sporadic and familial frontotemporal dementia. Hum Mutat. 2007 Sep;28(9):846-55. doi: 10.1002/humu.20520.

    PMID: 17436289RESULT

  • 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-Anterion C, Magne C, Vercelletto M, Bernard AM, Golfier V, Pasquier J, Michel BF, Namer I, Sellal F, Bochet J, Volteau M, Brice A, Meininger V; French Research Network on FTD/FTD-MND; Habert MO. Brain spect perfusion of frontotemporal dementia associated with motor neuron disease. Neurology. 2007 Jul 31;69(5):488-90. doi: 10.1212/01.wnl.0000266638.53185.e7. No abstract available.

    PMID: 17664410RESULT

  • 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 Broeckhoven C, Lambert JC, Verpillat P, Campion D, Habert MO, Dubois B, Brice A; French research network on FTD/FTD-MND. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. Brain. 2008 Mar;131(Pt 3):732-46. doi: 10.1093/brain/awn012. Epub 2008 Feb 1.

    PMID: 18245784RESULT

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Frontotemporal DementiaAmyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Frontotemporal Lobar DegenerationDementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTDP-43 ProteinopathiesNeurodegenerative DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesNeurocognitive DisordersMental DisordersSpinal Cord DiseasesMotor Neuron DiseaseNeuromuscular Diseases

Study Officials

  • Alexis Brice, MD

    Assistance Publique - Hôpitaux de Paris, University Paris 6

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 7, 2005

First Posted

September 12, 2005

Study Start

September 1, 2002

Study Completion

June 1, 2007

Last Updated

September 8, 2008

Record last verified: 2008-09

Locations

FR(15)