LIPAD - LRRK2 International Parkinson's Disease Study (LIPAD)

• ClinicalTrials.gov Identifier: NCT04214509
• Recruitment Status: Unknown
• First Posted: January 2, 2020
• Last Update Posted: February 27, 2020
• Sponsor: University of Luebeck
• Collaborator: CENTOGENE GmbH Rostock
• Information provided by (Responsible Party): Meike Kasten, University of Luebeck

Study Description

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.

Condition or disease
Parkinson's Disease and Parkinsonism

Study Design

• Study Type: Observational
• Estimated Enrollment: 4000 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: LIPAD - LRRK2 International Parkinson's Disease Study: an International, Multicenter, Epidemiological Observational Study
• Actual Study Start Date: January 20, 2020
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Groups and Cohorts

Group/Cohort
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

Outcome Measures

Primary Outcome Measures :

1. Epidemiology of LRRK2-positive patients [ Time Frame: 2 years ]
   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.

Secondary Outcome Measures :

1. Analysis of penetrance of LRRK2 mutations [ Time Frame: 2 years ]
   Penetrance rates (the proportion of individuals with LRRL2 mutation who exhibit clinical symptoms of Parkinson's disease) and phenotypes, and will try to predict penetrance in logistic regression models and quantify the influence of different factors impacting on penetrance.
2. Analysis of expressivity of LRRK2 mutations [ Time Frame: 2 years ]
   We will analyze expressivity (the degree in which a genotype is phenotypically expressed) of LRRK2 mutations. We will first define meaningful categories using our phenotypic data and then proceed to identify influencing factors.

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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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.

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.

Contacts and Locations

Contacts

Contact: Meike Kasten, Prof. Dr.; +4945131017518; lipad.ropad@neuro.uni-luebeck.de

Locations

Germany

Institute of Neurogenetics; Recruiting

Luebeck, Schelswig-Holstein, Germany, 23562

Contact: Tatiana Usnich, MD, PhD +4945131017518

Contact: Nathalie Schell, MD +4945131017518

Sponsors and Collaborators

University of Luebeck

CENTOGENE GmbH Rostock

Investigators

• Principal Investigator: Christine Klein, Prof. Dr.; Institute of Neurogenetics, University of Luebeck
• Principal Investigator: Meike Kasten, Prof. Dr.; Department of Psychiatry, University of Luebeck

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Usnich T, Vollstedt EJ, Schell N, Skrahina V, Bogdanovic X, Gaber H, Förster TM, Heuer A, Koleva-Alazeh N, Csoti I, Basak AN, Ertan S, Genc G, Bauer P, Lohmann K, Grünewald A, Schymanski EL, Trinh J, Schaake S, Berg D, Gruber D, Isaacson SH, Kühn AA, Mollenhauer B, Pedrosa DJ, Reetz K, Sammler EM, Valente EM, Valzania F, Volkmann J, Zittel S, Brüggemann 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.

• Responsible Party: Meike Kasten, Prof., University of Luebeck
• ClinicalTrials.gov Identifier: NCT04214509
• Other Study ID Numbers: LIPAD
• First Posted: January 2, 2020
• Last Update Posted: February 27, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: The Plan will be defined at later stages.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Meike Kasten, University of Luebeck:

genetic Parkinson's disease; LRRK2

Additional relevant MeSH terms:

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