Fox BioNet Project: LRRK2-002

FoxBioNet: LRRK2-002: Detection of LRRK2 Activity in Human Biospecimens

The overall objective of this study is to determine whether LRRK2 kinase activity and/or mitochondrial DNA (mtDNA) damage could serve as potential biomarkers in PD.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Procedure: Biofluid samplings

Detailed Description

Primary Objectives:

• Assess the levels of phosphorylated LRRK2 and LRRK2-phosphorylated Rabs, as measures of LRRK2 kinase activity, in PBMCs and neutrophils from LRRK2 PD, idiopathic PD, non-manifesting LRRK2 mutation carriers and healthy controls.
• Assess the levels of mtDNA damage in buffy coat from LRRK2 PD, idiopathic PD, non-manifesting LRRK2 mutation carriers and healthy controls.
• Correlate LRRK2 kinase activity to mtDNA damage in blood from LRRK2 PD, idiopathic-PD, non-manifesting LRRK2 mutation carriers and healthy controls.

Secondary Objectives:

• To assess the ability of the network to efficiently conduct a study involving biosample collection for PD research. Efficiency will be assessed using measures of the time taken to meet specific milestones within the study.
• To assess the ability of the network to collect high quality biospecimens adhering to agreed-upon, standardized protocols
• To gauge the willingness of participants to participate in subsequent Fox BioNet studies

• Study Type: Observational
• Enrollment (Actual): 114

Contacts and Locations

Study Locations

• United States
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Charles E. Schmidt College of Medicine, Florida Atlantic University
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

30 LRRK2 G2019S Manifesting carriers, 30 Idiopathic PD subjects, 30 LRRK2 G2019S Non-Manifesting Carriers, 30 Healthy Controls

Description

Inclusion Criteria:

LRRK2 Parkinson Disease (PD) Subjects:

• Patients must have confirmed LRRK2 mutation
• Patients must meet the MDS criteria for Parkinson's disease
• Disease duration: any
• Male or female age 30 years or older at time of PD diagnosis.

Idiopathic PD Subjects:

• Patients must meet the MDS criteria for Parkinson's disease.
• Disease duration: any
• Male or female age 30 years or older at time of PD diagnosis.

Non-manifesting LRRK2 mutation carriers:

• Patients must have confirmed LRRK2 mutation
• Male or female age 30 years or older at Screening.

Control (C) Subjects:

• Male or female age 30 years or older at Screening.

Exclusion Criteria:

LRRK2 Parkinson Disease (PD) Subjects:

• Inability to provide informed consent
• Participation in a blinded clinical trial of any kind or an unblinded trial of an investigational product that is not currently approved for use in humans.
• Treatment for cancer in the last 5 years.

Idiopathic PD Subjects:

• Inability to provide informed consent
• Participation in a blinded clinical trial of any kind or an unblinded trial of an investigational product that is not currently approved for use in humans.
• Treatment for cancer in the last 5 years.

Non-manifesting LRRK2 mutation carriers:

• Inability to provide informed consent
• Participation in a blinded clinical trial of any kind or an unblinded trial of an investigational product that is not currently approved for use in humans.
• Treatment for cancer in the last 5 years.

Control Subjects:

• Inability to provide informed consent
• Participation in a blinded clinical trial of any kind or an unblinded trial of an investigational product that is not currently approved for use in humans.
• Treatment for cancer in the last 5 years

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Idiopathic Parkinson's Disease patients; Up to 30 Parkinson's Disease patients will be enrolled.	Procedure: Biofluid samplings; Blood and Urine
Healthy Controls; Up to 30 Healthy Controls will be enrolled.	Procedure: Biofluid samplings; Blood and Urine
LRRK2 G2019S - Manifesting; Up to 30 LRRK2 G2019S Manifesting carriers will be enrolled.	Procedure: Biofluid samplings; Blood and Urine
LRRK2 G2019S - Non-Manifesting; Up to 30 LRRK2 G2019s Non-Manifesting carriers will be enrolled.	Procedure: Biofluid samplings; Blood and Urine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphorylated LRRK2 and LRRK2-phosphorylated Rabs	Assess the levels of phosphorylated LRRK2 and LRRK2-phosphorylated Rabs, as measures of LRRK2 kinase activity, in PBMCs and neutrophils from LRRK2 PD, idiopathic PD, non-manifesting LRRK2 mutation carriers and healthy controls.	7 months
mtDNA damage in buffy coat	Assess the levels of mtDNA damage in buffy coat from LRRK2 PD, idiopathic PD, non-manifesting LRRK2 mutation carriers and healthy controls.	7 months
Correlate LRRK2 kinase activity to mtDNA damage	Correlate LRRK2 kinase activity to mtDNA damage in blood from LRRK2 PD, idiopathic-PD, non-manifesting LRRK2 mutation carriers and healthy controls.	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the ability of the network to efficiently conduct a study	To assess the ability of the network to efficiently conduct a study involving biosample collection for PD research. Efficiency will be assessed using measures of the time taken to meet specific milestones within the study.	7 months
Assess the ability of the network to collect high quality biospecimens	To assess the ability of the network to collect high quality biospecimens adhering to agreed-upon, standardized protocols	7 months
To gauge the willingness of participants to participate in subsequent Fox BioNet studies	To gauge the willingness of participants to participate in subsequent Fox BioNet studies	7 Months

Collaborators and Investigators

• Sponsor: Michael J. Fox Foundation for Parkinson's Research
• Collaborators: University Health Network, Toronto; University of Rochester; Indiana University
• Investigators: Principal Investigator: Connie Marras, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2018
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 4, 2018

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Biomarker; Parkinson's Disease; LRRK2
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: LRRK2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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