Clinical trial NCT04214509: LIPAD - LRRK2 International Parkinson's Disease Study
Official title: LIPAD - LRRK2 International Parkinson's Disease Study: an International, Multicenter, Epidemiological Observational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Parkinson's Disease and Parkinsonism
Keywords: genetic Parkinson's disease
LRRK2
Lead sponsor: University of Luebeck
Sponsor class: OTHER
Collaborators: name: CENTOGENE GmbH Rostock
First posted: 2020-01-02
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Parkinson's disease or family members of participants with LRRK2 parkinsonism or members of a high risk population with an early PD onset, able to provide informed consent and equal or older than 18 years old.

Brief summary: The study aims to identify and systematically characterize Parkinson's patients with mutations in the LRRK2 gene. In about 90% of Parkinson's patients the cause of the disease is unclear. Based on current knowledge, it can be assumed that there are several causes and that the causes may be differ between patients; this makes research into the pathogenesis and possible therapies very difficult. In the case of monogenic Parkinson's diseases, which are due to changes in one gene (e.g. LRRK2), the function of the gene and possible disease mechanisms can be investigated. LRRK2-associated Parkinson's syndrome is clinically indistinguishable from idiopathic Parkinson's disease. It is inherited autosomal dominant, that means if one of the two gene copies is altered, the disease occurs. However, the disease does not occur in every mutation carrier, the penetrance is reduced and the mechanisms for that are still unclear. Ideally, knowledge of what influences penetrance could make it possible to exert targeted influence and prevent the disease. The comprehensive investigation of mechanisms of reduced penetrance but also of the effects of the mutation itself requires systematic investigations of as many affected persons as possible. We therefore aim to identify 4,000 people internationally, of them 1,500 with LRRK2-associated Parkinson's syndrome, 500 with LRRK2-mutations but without Parkinson's symptoms, 500 without mutations and without Parkinson's symptoms, 500 Parkinson patients with mutations in other genes than LRRK2 and 1,000 patients with idiopathic Parkinson's disease from the same populations. The participants will undergo a comprehensive survey on Parkinson's symptoms, concomitant diseases, environmental factors and medication and there is the possibility of more detailed genetic examinations. Participants will be asked to donate samples of blood, urine and household dust.


Eligibility criteria: Inclusion Criteria:

* Informed consent is obtained from the participant.
* The participant is clinically diagnosed with Parkinson's disease or the individual is a family member of a participant with LRRK2 parkinsonism or is a member of a high risk population with an early PD onset.
* The participant is equal to or older than 18 years old.

Exclusion Criteria:

* Inability to provide informed consent.
* The participant is not suffering from Parkinson's disease or the individual is not a family member of a participant with LRRK2 parkinsonism or is not a member of a high risk population.
* The participant is younger than 18 years old.
* Previously enrolled in the study.
* Participant in custody.

Primary outcomes:
measure: Epidemiology of LRRK2-positive patients
timeFrame: 2 years
Secondary outcomes:
measure: Analysis of penetrance of LRRK2 mutations
timeFrame: 2 years
measure: Analysis of expressivity of LRRK2 mutations
timeFrame: 2 years
Other outcomes:
Locations:
city: Luebeck
country: Germany
facility: Institute of Neurogenetics
state: Schelswig-Holstein
Study officials:
affiliation: Institute of Neurogenetics, University of Luebeck
name: Christine Klein, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry, University of Luebeck
name: Meike Kasten, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Usnich T, Vollstedt EJ, Schell N, Skrahina V, Bogdanovic X, Gaber H, Forster TM, Heuer A, Koleva-Alazeh N, Csoti I, Basak AN, Ertan S, Genc G, Bauer P, Lohmann K, Grunewald A, Schymanski EL, Trinh J, Schaake S, Berg D, Gruber D, Isaacson SH, Kuhn AA, Mollenhauer B, Pedrosa DJ, Reetz K, Sammler EM, Valente EM, Valzania F, Volkmann J, Zittel S, Bruggemann N, Kasten M, Rolfs A, Klein C; LIPAD Study Group. LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol: Deep Phenotyping of an International Genetic Cohort. Front Neurol. 2021 Aug 9;12:710572. doi: 10.3389/fneur.2021.710572. eCollection 2021.