Clinical, Molecular and by Neuroimaging of LRRK2 Mutations (LRRK2)

• ClinicalTrials.gov Identifier: NCT01085227
• Recruitment Status: Unknown
• First Posted: March 11, 2010
• Last Update Posted: September 27, 2012
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Information provided by (Responsible Party): Institut National de la Santé Et de la Recherche Médicale, France

Study Description

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.

Condition or disease
Parkinson's Disease

Study Design

• Study Type: Observational
• Estimated Enrollment: 50 participants
• Observational Model: Family-Based
• Time Perspective: Prospective
• Official Title: Clinical, Molecular and by Neuroimaging Characterization of Monogenic Forms of Parkinsonism Syndromes: Mutations of the LRRK2 Gene.
• Study Start Date: April 2008

Groups and Cohorts

Group/Cohort
Patients carrier of a LRRK2 mutation
Asymptomatic relatives of LRRK2 patients

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

French population

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

Contacts and Locations

Contacts

Contact: Alexis BRICE, MD; +331 42 16 21 82; alexis.brice@upmc.fr

Locations

France

CEA - Service Hospitalier Frédéric Joliot; Active, not recruiting

Orsay, France, 91401

Pitie-Salpetriere Hospital; Recruiting

Paris, France, 75013

Contact: BRICE alexis.brice@upmc.fr

Sub-Investigator: Alexandra DURR, MD, PhD

Principal Investigator: Alexis BRICE, MD

Sub-Investigator: Stéphane LEHERICY, MD, PhD

Sub-Investigator: Jean-Christophe CORVOL, MD, PHD

Sub-Investigator: Isabelle ARNULF, MD, PhD

Sub-Investigator: Yves AGID, MD, PhD

Sub-Investigator: Perrine CHARLES, MD, PhD

Sub-Investigator: Mathieu ANHEIM, MD, PhD

Sub-Investigator: Anne-Marie BONNET, MD

Sub-Investigator: Marie VIDAILHET, MD

Sponsors and Collaborators

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

More Information

• Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• ClinicalTrials.gov Identifier: NCT01085227
• Other Study ID Numbers: C06-16.1; 2007-A00169-44 ( Registry Identifier: IDRCB )
• First Posted: March 11, 2010
• Last Update Posted: September 27, 2012
• Last Verified: January 2012

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:

Parkinson's disease; LRRK2; asymptomatic carriers

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases