Clinical, Molecular and by Neuroimaging of LRRK2 Mutations

NCT ID: NCT01085227

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2017-10-11

Brief Summary

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.

Conditions

Parkinson's Disease

Study Design

• Observational Model Type: FAMILY_BASED
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients carrier of a LRRK2 mutation

No interventions assigned to this group

Asymptomatic relatives of LRRK2 patients

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CEA - Service Hospitalier Frédéric Joliot

Orsay, , France

Pitie-Salpetriere Hospital

Paris, , France

Countries

France

Other Identifiers

2007-A00169-44

Identifier Type: REGISTRY

Identifier Source: secondary_id

C06-16.1

Identifier Type: -

Identifier Source: org_study_id