FoxBioNet: ECV (Extracellular Vesicle) 004

The goal of this study is to identify reliable markers of LRRK2 activity in human CSF.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Procedure: Lumbar Puncture

Detailed Description

Specific aims of this project are:

Primary Objectives:

To evaluate each assay performance for its ability to detect LRRK2, its activity and/or the detection and activity of the pathways it impacts using a variety of different approaches (quantitative western blot, immunoassays and LC-MS). Assay performance will be assessed and those demonstrating high sensitivity and consistency will be considered for further development.

Secondary Objectives:

To assess the ability of the assay or a combination of assays to differentiate pathogenic LRRK2 variant manifesting and non-manifesting carriers, idiopathic PD and healthy non-carriers.

• Study Type: Observational
• Enrollment (Actual): 140

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • New York
    • New York, New York, United States, 10032
      • The Trustees of Columbia University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences Univeristy
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • The Trustees of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Approximately 140 participants will be enrolled to participate in this study, with a goal of enrolling 30 non-manifesting LRRK2 carriers, 30 LRRK2 Parkinson's Disease (PD), 40 idiopathic PD, and 40 healthy controls.

Description

Non-manifesting LRRK2 mutation carriers

Inclusion:

• Ability to provide informed consent
• Confirmed LRRK2 G2019S mutation
• Age 30 years or older at date of informed consent.

Exclusion:

• Inability to provide informed consent
• Known GBA mutation carrier
• 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. Participants that have had a 6 - month washout period between ending participation in a clinical trial with an investigational agent and enrollment into the ECV-004 study are eligible.
• The presence of rest tremor, bradykinesia or rigidity.
• The presence of any other neurological sign that in the opinion of the site investigator raises suspicion for an atypical parkinsonian syndrome (e.g. supranuclear gaze palsy)
• Treatment for cancer in the last 5 years or cancer patient receiving immunotherapy or targeted therapy. Individuals with cancers that have not been treated with systemic chemotherapy, immunotherapy, targeted therapies or radiation therapy are eligible to enroll in the study.
• Diagnosis of an autoimmune disorder
• Current treatment with anticoagulants that might preclude safe completion of the lumbar puncture and that cannot be safely paused in the opinion of the site investigator.
• Any condition that, in the investigator's opinion, precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
• Diagnosis of dementia
• Pregnant females, if fluoroscopy is needed to obtain the spinal fluid sample

LRRK2 Parkinson Disease (PD) Participants:

Inclusion:

• Ability to provide informed consent
• Confirmed LRRK2 G2019S mutation
• Meet the MDS criteria for Parkinson's disease
• Disease duration: any
• Age 30 years or older at time of PD diagnosis.

Exclusion:

• Known GBA mutation carrier
• 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. Participants that have had a 6 - month washout period between ending participation in a clinical trial with an investigational agent and enrollment into the ECV-004 study are eligible.
• Treatment for cancer in the last 5 years or cancer patient receiving immunotherapy or targeted therapy. Individuals with cancers that have not been treated with systemic chemotherapy, immunotherapy, targeted therapies or radiation therapy are eligible to enroll in the study.
• Diagnosis of an autoimmune disorder
• Current treatment with anticoagulants that might preclude safe completion of the lumbar puncture and that cannot be safely paused in the opinion of the site investigator.
• Any condition that, in the investigator's opinion, precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
• Diagnosis of dementia
• Pregnant females, if fluoroscopy is needed to obtain the spinal fluid sample

Idiopathic PD (iPD) Particpants:

Inclusion:

• Ability to provide informed consent
• Meet the MDS criteria for Parkinson's disease.
• Disease duration: any
• Age 30 years or older at time of PD diagnosis.

Exclusion:

• Known LRRK2 G2019S and/or GBA mutation carrier
• 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. Participants that have had a 6 - month washout period between ending participation in a clinical trial with an investigational agent and enrollment into the ECV-004 study are eligible.
• Treatment for cancer in the last 5 years or cancer patient receiving immunotherapy or targeted therapy. Individuals with cancers that have not been treated with systemic chemotherapy, immunotherapy, targeted therapies or radiation therapy are eligible to enroll in the study.
• Diagnosis of an autoimmune disorder
• Current treatment with anticoagulants that might preclude safe completion of the lumbar puncture and that cannot be safely paused in the opinion of the site investigator.
• Any condition that, in the investigator's opinion, precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
• Diagnosis of dementia
• Pregnant females, if fluoroscopy is needed to obtain the spinal fluid sample

Control (C) Participants:

Inclusion:

• Ability to provide informed consent
• Age 30 years or older at date of informed consent.

Exclusion:

• Known GBA mutation carrier
• In the absence of prior genetic testing for LRRK2 G2019S mutations: Family history of Parkinson's disease is an exclusion criterion. If genetic testing for LRRK2 G2019S mutations has been performed and is negative, individuals with a family history of PD may be enrolled.
• The presence of rest tremor, bradykinesia or rigidity.
• The presence of any other neurological sign that in the opinion of the site investigator raises suspicion for an atypical parkinsonian syndrome (e.g. supranuclear gaze palsy)
• Treatment for cancer in the last 5 years or cancer patient receiving immunotherapy or targeted therapy. Individuals with cancers that have not been treated with systemic chemotherapy, immunotherapy, targeted therapies or radiation therapy are eligible to enroll in the study.
• Diagnosis of an autoimmune disorder.
• Current treatment with anticoagulants that might preclude safe completion of the lumbar puncture and that cannot be safely paused in the opinion of the site investigator.
• Any condition that, in the investigator's opinion, precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
• Diagnosis of dementia
• Pregnant females, if fluoroscopy is needed to obtain the spinal fluid sample

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non-manifesting LRRK2 mutation carriers; Patients must have confirmed LRRK2 G2019S mutation Age 30 years or older at date of informed consent.	Procedure: Lumbar Puncture; Lumbar Puncture for collection of Cerebrospinal Fluids; Other Names: Whole Blood Collection
LRRK2 Parkinson Disease (PD) Participants: Patients must have confirmed LRRK2 G2019S mutation Patients must meet the MDS criteria for Parkinson's disease Disease duration: any Age 30 years or older at time of PD diagnosis.	Procedure: Lumbar Puncture; Lumbar Puncture for collection of Cerebrospinal Fluids; Other Names: Whole Blood Collection
Idiopathic PD (iPD) Particpants: Patients must meet the MDS criteria for Parkinson's disease. Disease duration: any Age 30 years or older at time of PD diagnosis.	Procedure: Lumbar Puncture; Lumbar Puncture for collection of Cerebrospinal Fluids; Other Names: Whole Blood Collection
Control (C) Participants: Age 30 years or older at date of informed consent.	Procedure: Lumbar Puncture; Lumbar Puncture for collection of Cerebrospinal Fluids; Other Names: Whole Blood Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assay Evaluation	Evaluate each assay performance for ability to detect LRRK2, its activity and/or the detection and activity of the pathways it impacts using a variety of different approaches (quantitative western blot, immunoassays and LC-MS).	1 year

Collaborators and Investigators

• Sponsor: Michael J. Fox Foundation for Parkinson's Research
• Collaborators: University Health Network, Toronto; University of Rochester; Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Parkinson's Disease; CSF; 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: ECV-004

Drug and device information, study documents

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