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Identification of New FTLD Genes (FTLD-Exome)

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ClinicalTrials.gov Identifier: NCT02363062
Recruitment Status : Unknown
Verified August 2016 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was:  Recruiting
First Posted : February 13, 2015
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The major objective of the project is to map/identify new loci/genes, by a combination of whole exome sequencing and genome-wide linkage in autosomal dominant FTLD families excluded for known mutations.

Several secondary goals will be attained in the course of during the project:

For each novel gene identified in this project, we will determine the spectrum of mutations, evaluate their frequency and characterize the associated phenotypes. This will allow us to establish genotype-phenotype correlations in a large number of families, which will improve the nosology of these disorders and the diagnostic procedures;


Condition or disease
Frontotemporal Lobar Degeneration

Detailed Description:

Background and justification of the research. In France, 6,000 to 8,000 patients are affected by frontotemporal lobar degeneration (FTLD). FTLD are degenerative dementias related to Alzheimer's disease, characterized by behavioural, language and cognitive disorders beginning in the sixth decade. The genetic forms of FTLD are frequent (30-50% of the patients), but the genes responsible for 30-40% of familial FTLD are still unknown. At present, no molecular diagnosis can be proposed for 30% of the FTLD families and patients, for which the responsible genes are still unknown. No presymptomatic testing can be proposed either to at-risk relatives in these families.

Objectives.

  1. The principal objective of this proposal is to identify one or several genes responsible for FTLD.
  2. The secondary objectives are to:

    • evaluate the relative frequency of identified genes;
    • describe the phenotypes associated with the mutations in these genes;
    • establish phenotype-genotype correlations in order to improve the diagnostic procedures and strategies;
    • develop new genetic diagnostic analyses in the near future.

Project The patients will be recruited in three hospitals (Paris Salpetriere, Limoges, Lille). These three centers are partners of a national clinico-genetic network of 20 french centers experts in FTLD/FTLD-ALS, coordinated by Dr. I Le Ber. The participants in this network have collaborated for the last 15 years, and have already recruited over 1,000 patients with FTLD. Sequencing of known genes in these families allowed the identification of 150 families with an autosomal dominant form of FTLD not associated with a known mutation. Through the network, we aim to recruit 400 new patients with FTLD during the 4 years of the project. This estimation is based on the annual recruitment of the network during the last two years.

In this project, the 30 most informative families will be extended (440 patients and relatives sampled).

The combination of whole exome sequencing with genetic linkage studies in FTLD families without known mutations, and the large number of families included in this project, are two major points that should lead to the identification of several new genes. When causative genes are identified, we will establish the frequencies of mutations, extend the mutational spectrum, describe the clinical phenotypes and establish phenotype-genotype correlations. Genetic parameters such as penetrance will be analyzed.


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Study Type : Observational
Estimated Enrollment : 440 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Identification of New Genes Causing Frontotemporal Lobar Degeneration by Whole Exome Sequencing and Characterization of the Associated Phenotypes
Actual Study Start Date : February 2, 2015
Estimated Primary Completion Date : February 1, 2019
Estimated Study Completion Date : February 1, 2019

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. whole exome sequencing [ Time Frame: Day 1 ]
    genes responsible for FTLD /Blood samples will be collected by a nurse, during a single consultation or hospitalization


Biospecimen Retention:   Samples With DNA
Blood samples will be collected by a nurse, during a single consultation or hospitalization


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients affected by FTLD±ALS according to the international diagnosis criteria and their relatives
Criteria

Patients are included if they:

i) are affected by FTLD±ALS according to the international diagnosis criteria and ii) Have (or their legal representatives have) given signed written informed consent for the research.

iii) are affiliated to social security or beneficiary of such régime

Relatives are included if they:

i) are aged >18 years and ii) Have signed an informed consent for the research. are affiliated to social security or beneficiary of such


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 ClinicalTrials.gov identifier (NCT number): NCT02363062


Contacts
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Contact: Isabelle LE BER, MD, PhD (+33) 01 57 27 46 79 isabelle.leber@upmc.fr

Locations
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France
Pitié Salpetriere Hospital Recruiting
Paris, France, 75013
Contact: Isabelle LE BER         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Isabelle LE BER, MD, PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02363062     History of Changes
Other Study ID Numbers: 2014-A00157-40
First Posted: February 13, 2015    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:
frontotemporal lobar degeneration
genes
whole exome sequencing

Additional relevant MeSH terms:
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Frontotemporal Lobar Degeneration
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Neurocognitive Disorders
Mental Disorders