- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01085227
Clinical, Molecular and by Neuroimaging of LRRK2 Mutations (LRRK2)
Clinical, Molecular and by Neuroimaging Characterization of Monogenic Forms of Parkinsonism Syndromes: Mutations of the LRRK2 Gene.
Besides Parkinson's disease (PD), it exists rare parkinsonian syndromes clinically close to PD and that correspond to Mendelian entities. Autosomal dominant forms are mainly associated with mutations of alpha synuclein and LRRK2/dardarin genes, whereas autosomal recessive forms are due to mutations in Parkin, Pink1 and DJ-1 genes. This entities are still unknown on the clinical, genetic and metabolic " au plan ".
Throughout a national network of 15 specialized centres in movement disorders, coordinated by the team of the neurogenetics reference centre at the Pitié-Salpêtrière Hospital (Alexis Brice), we propose to precise the relative frequency, the molecular bases and abnormalities in functional neuroimaging associated with the LRRK2 gene mutations, the most frequently implicated in the autosomal dominant forms. Due to the relative rarity of this parkinsonian syndrome, we will perform at the same time a retrospective study in cases and families already collected by the national network (300 isolated cases and 300 families) and a prospective study. The network will recruit 100 isolated cases and 40 familial cases yearly, with precise diagnosis tools. The genetic analysis will evaluate the relative frequency of the LRRK2 mutations and their spectrum in the French population. Phenotype-genotype correlations will be performed to better orientate the molecular diagnosis, in order to improve the genetic counselling and reduce costs of these analyses. In the case of LRRK2 mutations, a genetic investigation will be proposed to the families, with a specific care to at-risk cases. A detailed phenotypic evaluation of patients and at-risk cases will be proposed (neurological, neuropsychiatric and behavioural) at the CIC Pitié-Salpêtrière and also in imaging, for 15 patients and 40 of their relatives (20 carriers and 20 non-carriers of the LRRK2 mutation). The TEP study will evaluate the dopaminergic function (fluorodopa capture) and will measure the dopamine transporter (DAT). The structural MRI evaluation will search for possible associated structural morphologic abnormalities. The functional MRI evaluation will search for dysfunction of motor circuit during the movement realisation. These examinations will be performed at two years of interval for appreciate the evolution of the disease. This study will allow to better characterize the parkinsonian syndromes due to LRRK2 mutations and also to better characterize the presymptomatic phase, which is subject to controversies in idiopathic PD. The feasibility of this project is assured by the expertise of the collaborative centres and by the inclusion of a retrospective cohort, combined to a prospective cohort, which will allow to recruit sufficient patients and at-risk relatives for a rare genetic entity.
Studieoversigt
Status
Betingelser
Undersøgelsestype
Tilmelding (Forventet)
Kontakter og lokationer
Studiesteder
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Orsay, Frankrig, 91401
- Aktiv, ikke rekrutterende
- CEA - Service Hospitalier Frédéric Joliot
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Paris, Frankrig, 75013
- Rekruttering
- Pitié-Salpêtrière Hospital
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Underforsker:
- Alexandra DURR, MD, PhD
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Kontakt:
- BRICE
- E-mail: alexis.brice@upmc.fr
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Underforsker:
- Stéphane Lehéricy, MD, PhD
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Underforsker:
- Jean-Christophe CORVOL, MD, PHD
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Underforsker:
- Isabelle ARNULF, MD, PhD
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Underforsker:
- Yves AGID, MD, PhD
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Underforsker:
- Perrine CHARLES, MD, PhD
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Underforsker:
- Mathieu ANHEIM, MD, PhD
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Underforsker:
- Anne-Marie BONNET, MD
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Underforsker:
- Marie VIDAILHET, MD
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inclusion Criteria:
- To be over 18 years old
- Diagnosis of Parkinson's disease
- To be a first-degree relative to a LRRK2 patient
- Ability to understand the aim of the study
- Ability to sign the consent form
Exclusion Criteria:
- Non ability to understand the aim of the study
- Non ability to sign the consent form
- Inability to do a MRI
- Pregnant women or absence of an effective contraception
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: Familiebaseret
- Tidsperspektiver: Fremadrettet
Kohorter og interventioner
Gruppe / kohorte |
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Patients carrier of a LRRK2 mutation
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Asymptomatic relatives of LRRK2 patients
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Samarbejdspartnere og efterforskere
Datoer for undersøgelser
Studer store datoer
Studiestart
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- C06-16.1
- 2007-A00169-44 (Registry Identifier: IDRCB)
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