Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
|First Received Date ICMJE||September 7, 2005|
|Last Updated Date||September 5, 2008|
|Start Date ICMJE||September 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00159198 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Amyotrophic Lateral Sclerosis and Frontotemporal Dementia|
|Official Title ICMJE||Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia|
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.
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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Time Perspective: Retrospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
|Sampling Method||Non-Probability Sample|
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.
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Completion Date||June 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 90 Years|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||France|
|NCT Number ICMJE||NCT00159198|
|Other Study ID Numbers ICMJE||CRC01107, P011023|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Isabelle BRINDEL, Department Clinical Research of Developpement|
|Study Sponsor ICMJE||Assistance Publique - Hôpitaux de Paris|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Assistance Publique - Hôpitaux de Paris|
|Verification Date||September 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP