Frontotemporal DementiaNCT00159198
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
An observational study of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 15 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
- How many people
- 400 participants
- Where
- 15 sitesFrance
- Study dates
- Sep 2002to Jun 2007
- 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 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Minors, persons refusing to sign the informed consent
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites
CHU de la Côte de Nacre
Caen, 14000
Centre Hospitalier Universitaire de Lille
Lille, 59000
Hôpital La Timone
Marseille, 13005
Hôpital Sainte-Marguerite
Marseille, 13009
Hôpital Guillaume et René Laënnec
Nantes, 44000
Hôpital de l'Archet
Nice, 06000
Hôpital Pitié-Salpêtrière - Centre du Langage-Neuropsychologie
Paris, 75013
Hôpital Pitié-Salpêtrière - Fédération de Neurologie
Paris, 75013
Hôpital Pitié-Salpêtrière
Paris, 75013
Hôpital Pontchaillou
Rennes, 35000
Hôpital Charles Nicolle
Rouen, 76000
Centre Hospitalier
Saint-Brieuc, 22000
Hôpital Bellevue
Saint-Etienne, 42000
Hôpital Civil
Strasbourg, 67000
Hôpital Purpan
Toulouse, 31000
About this study
Official title: 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.
Read the 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.
- Keywords
- Amyotrophic lateral sclerosis, Frontotemporal dementia, Mutations spectrum, Linkage studies, Genetic epidemiology
- Medical subject headings
- Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startSep 2002
- Study completionJun 2007
Why it stopped: Completed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Frontotemporal DementiaStudies 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Investigators
- Alexis Brice, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris, University Paris 6
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00159198
- Sponsor's protocol ID
- CRC01107
- Other IDs
- P011023
- Status last verified
- Sep 2008
- First submitted
- 7 Sep 2005
- Last updated
- 8 Sep 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17071924van 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.
PubMed 17345602Le 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.
PubMed 17436289Guedj 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.
PubMed 17664410Le 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.
PubMed 18245784
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
- ClinicalTrials.gov ID
- NCT00159198
- Acronym / sponsor ID
- CRC01107
- Keywords
- Amyotrophic lateral sclerosis, Frontotemporal dementia, Mutations spectrum, Linkage studies, Genetic epidemiology
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2002
- Study completion
- Jun 2007 (actual)
- First posted
- 12 Sep 2005 (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.
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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Minors, persons refusing to sign the informed consent
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
Not reported in the source record.
Results and safety
The study was stopped early (reason given: Completed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2008.
- Results publication: PubMed 17071924Le 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.
- Results publication: PubMed 17345602van 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.
- Results publication: PubMed 17436289Le 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.
- Results publication: PubMed 17664410Guedj 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.
- Results publication: PubMed 18245784Le 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.
- Related InfoLink provided by the sponsor.
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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.
Alexis Brice, MD principal investigator
Assistance Publique - Hôpitaux de Paris, University Paris 6
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 15 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. 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: stopped early, as of the sponsor's last update on 8 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites 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?
The study was stopped early (reason given: Completed). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00159198, which also lists 5 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 8 Sep 2008.