Frontotemporal Lobar DegenerationFTLD-ExomeNCT02363062
Identification of New FTLD Genes
An observational study of Frontotemporal Lobar Degeneration, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Frontotemporal Lobar Degeneration
- How many people
- 440 participants
- Where
- 1 siteFrance
- Study dates
- 2 Feb 2015to 1 Feb 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients affected by FTLD±ALS according to the international diagnosis criteria and their relatives
Patients are included if they:
- 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:
- are aged >18 years and ii) Have signed an informed consent for the research. are affiliated to social security or beneficiary of such
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Pitié Salpetriere Hospital
Paris, 75013
Isabelle LE BER
About this study
Official title: Identification of New Genes Causing Frontotemporal Lobar Degeneration by Whole Exome Sequencing and Characterization of the Associated Phenotypes
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;
Read the 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.
- The principal objective of this proposal is to identify one or several genes responsible for FTLD.
- 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.
- Conditions
- Frontotemporal Lobar Degeneration
- Keywords
- frontotemporal lobar degeneration, genes, whole exome sequencing
- Medical subject headings
- Frontotemporal Lobar Degeneration
What is being measured
The primary outcome is the main question the study is designed to answer.
whole exome sequencing
genes responsible for FTLD /Blood samples will be collected by a nurse, during a single consultation or hospitalization
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2015 (estimated)
- Study start2 Feb 2015
- Primary completion1 Feb 2019 (estimated)
- Study completion1 Feb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Frontotemporal Lobar DegenerationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Isabelle LE BER, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02363062
- Sponsor's protocol ID
- 2014-A00157-40
- Acronym
- FTLD-Exome
- Status last verified
- Aug 2016
- First submitted
- 9 Feb 2015
- Last updated
- 29 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Ceslis A, Argall R, Henderson RD, McCombe PA, Robinson GA. The spectrum of language impairments in amyotrophic lateral sclerosis. Cortex. 2020 Nov;132:349-360. doi: 10.1016/j.cortex.2020.09.003. Epub 2020 Sep 18.
PubMed 33031977Didic M, Aglieri V, Tramoni-Negre E, Ronat L, Le Ber I, Ceccaldi M, Belin P, Felician O. Progressive phonagnosia in a telephone operator carrying a C9orf72 expansion. Cortex. 2020 Nov;132:92-98. doi: 10.1016/j.cortex.2020.05.022. Epub 2020 Aug 10.
PubMed 32961393
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of New Genes Causing Frontotemporal Lobar Degeneration by Whole Exome Sequencing and Characterization of the Associated Phenotypes
- ClinicalTrials.gov ID
- NCT02363062
- Acronym / sponsor ID
- FTLD-Exome / 2014-A00157-40
- Conditions
- Frontotemporal Lobar Degeneration
- Keywords
- frontotemporal lobar degeneration, genes, whole exome sequencing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 440 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 2 Feb 2015 (actual)
- Primary completion
- 1 Feb 2019 (estimated)
- Study completion
- 1 Feb 2019 (estimated)
- First posted
- 13 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
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.
- The principal objective of this proposal is to identify one or several genes responsible for FTLD.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients affected by FTLD±ALS according to the international diagnosis criteria and their relatives
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2017.
- Derived from this study: PubMed 33031977Ceslis A, Argall R, Henderson RD, McCombe PA, Robinson GA. The spectrum of language impairments in amyotrophic lateral sclerosis. Cortex. 2020 Nov;132:349-360. doi: 10.1016/j.cortex.2020.09.003. Epub 2020 Sep 18.
- Derived from this study: PubMed 32961393Didic M, Aglieri V, Tramoni-Negre E, Ronat L, Le Ber I, Ceccaldi M, Belin P, Felician O. Progressive phonagnosia in a telephone operator carrying a C9orf72 expansion. Cortex. 2020 Nov;132:92-98. doi: 10.1016/j.cortex.2020.05.022. Epub 2020 Aug 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Isabelle LE BER, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Frontotemporal Lobar Degeneration, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Isabelle LE BER, MD, PhD ((+33) 01 57 27 46 79, isabelle.leber@upmc.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
whole exome sequencing (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02363062, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2017.