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

LIPAD - LRRK2 International Parkinson's Disease Study: an International, Multicenter, Epidemiological Observational Study

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.

Study Overview

• Status: Unknown
• Conditions: Parkinson's Disease and Parkinsonism

• Study Type: Observational
• Enrollment (Anticipated): 4000

Contacts and Locations

Study Locations

• Germany
  • Schelswig-Holstein
    • Luebeck, Schelswig-Holstein, Germany, 23562
      • Recruiting
      • Institute of Neurogenetics
      • Contact: Tatiana Usnich, MD, PhD; Phone Number: +4945131017518
      • Contact: Nathalie Schell, MD; Phone Number: +4945131017518

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

5

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of penetrance of LRRK2 mutations	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 years
Analysis of expressivity of LRRK2 mutations	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.	2 years

Collaborators and Investigators

• Sponsor: University of Luebeck
• Collaborators: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 24, 2019
• First Submitted That Met QC Criteria: December 27, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 26, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: genetic Parkinson's disease; LRRK2
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders
• Other Study ID Numbers: LIPAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The Plan will be defined at later stages.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No