LIPAD - LRRK2 International Parkinson's Disease Study

NCT04214509 | Unknown

• 1 other identifier: LIPAD
• Study Type: observational
• Target: 4,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease and Parkinsonism

Keywords

genetic Parkinson's disease; LRRK2

Outcome Measures

Primary Outcomes (1)

• Epidemiology of LRRK2-positive patients

  Description of the frequency of all important clinical signs and symptoms including non-motor signs and factoring in the most important influencing factors such as sex, disease duration, and medication. We will report raw and corrected frequencies with 95% confidence intervals.

  2 years

Secondary Outcomes (2)

• Analysis of penetrance of LRRK2 mutations

  2 years

• Analysis of expressivity of LRRK2 mutations

  2 years

Study Arms (5)

PD + LRRK2

Patients with LRRK2-associated Parkinson's syndrome

no PD + LRRK2

Participants with LRRK2-mutations but without Parkinson's symptoms

no PD + no LRRK2

Participants without mutations and without Parkinson's symptoms

PD+ other than LRRK2

Parkinson patients with mutations in other genes than LRRK2

PD+ no LRRK2

Patients with idiopathic Parkinson's disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Luebeck: lead
• CENTOGENE GmbH Rostock: collaborator

Study Sites (1)

Institute of Neurogenetics

Lübeck, Schelswig-Holstein, 23562, Germany

RECRUITING

Related Publications (1)

• 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.

  PMID: 34475849 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine samples will be biochemically analysed to determine factors leading to incomplete penetrance in LRRK2 positive carriers and biomarkers of Parkinson's disease. In blood samples DNA and DNA methylation, RNA and proteins will be analysed. Urine samples will be analysed using NGS-based sequencing of the mitochondrial genome and search for mitochondrial DNA deletions. Dust will be analysed toxicologically.

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Christine Klein, Prof. Dr.

  Institute of Neurogenetics, University of Luebeck

  PRINCIPAL INVESTIGATOR

• Meike Kasten, Prof. Dr.

  Department of Psychiatry, University of Luebeck

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meike Kasten, Prof. Dr.

CONTACT

+4945131017518; lipad.ropad@neuro.uni-luebeck.de

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 24, 2019
• First Posted: January 2, 2020
• Study Start: January 20, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 27, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)