The GBA Multimodal Study in Parkinson's Disease

Multimodal Molecular Imaging and Biometric Analysis in GBA-PD and Asymptomatic GBA-mutation Carriers

This study plans to analyze the molecular and clinical mechanisms of the relationship between the GBA mutations and Parkinson's disease. This will be assessed through the use of advanced neuroimaging techniques called PET (positron emission tomography) to study the accumulation of the tau protein and the dysfunction of acetylcholine and dopamine in the brain of people with a mutation in the GBA gene, with and without Parkinson's disease. The ingestigators will also use a technology-based assessment to study the typing patterns as possible biomarkers of early motor dysfunctions.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Gaucher Disease; GBA Gene Mutation
• Intervention / Treatment: Diagnostic test: PET scan; Diagnostic test: neuroQWERTY

Detailed Description

Study Rationale: People who have a mutation in the GBA gene have a higher risk of developing Parkinson's disease (PD) and, if they have PD, are more likely to have cognitive decline and dementia. Cognitive problems in people with PD is related to dysfunction of the brain chemical acetylcholine and likely to the accumulation of the tau protein in the brain. Another observation in previous studies is that analyzing the patterns of typing into a computer can help differentiate healthy people from people with PD.

Hypothesis: The investigators hypothesize that people with GBA-related PD will have higher acetylcholine dysfunction and tau accumulation compared with non-GBA patients, and that these changes may start in the asymptomatic phase (i.e., people with the mutation but without symptoms of PD). The investigators also believe that the investigators will be able to detect subjects with higher degree of dopamine loss just by analyzing the way they type into a computer.

Study Design: The investigators will recruit 25 subjects with a GBA mutation (10 subjects with PD and 15 asymptomatic carriers). All the participants will have a clinical evaluation and a typing session, and subsequently will undergo a brain MRI and three PET scans with a tau tracer, an acetylcholine tracer, and a dopaminergic tracer. A blood sample will also be taken for the analysis of GCase (the enzyme related to the GBA mutation).

Impact on Diagnosis/Treatment of Parkinson's Disease: The results will help understand the changes that take place in the brain of people with GBA-related Parkinson's disease, and hopefully will shed light also on the pathophysiology of non-GBA-related Parkinson's, as well as on the molecular correlates of cognitive decline, especially in its early stage. The typing data along with dopaminergic imaging will clarify the possible role of using typing patterns to identify subjects with early stage Parkinson's disease.

Next Steps for Development: The findings of this study may help identify biomarkers for cognitive decline in early Parkinson's disease, with a potential role in clinical trials. Also, if the hypothesis on the typing is confirmed, this approach may be studied in larger cohorts for early diagnosis of Parkinson's in other at-risk populations.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Michele Matarazzo, MD; Phone Number: +1-604-822-7764; Email: michele.matarazzo@ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Recruiting
      • Pacific Parkinson's Research Centre | University of British Columbia
      • Contact: Jess McKenzie; Phone Number: +1-604-822-7764; Email: jess.mckenzie@ubc.ca
      • Principal Investigator: A Jon Stoessl, MD
• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Matthew Brodsky, MD
  • Washington
    • Seattle, Washington, United States, 98108-1595
      • Recruiting
      • University of Washington
      • Principal Investigator: Cyrus P Zabetian, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

People with a known pathogenic GBA gene mutation with or without PD.

Description

Inclusion Criteria:

• heterozygous for a pathogenic GBA mutation (e.g., p.L444P, p.N370S) or polymorphism;
• age 18 to 80 years.

Exclusion Criteria:

• co-occurrence of other neurological disorders;
• implants that contraindicate the MRI scanning (e.g. cardiac pacemaker, ferromagnetic implants or devices);
• severe claustrophobia;
• intolerance to antiparkinsonian drug withdrawal (for GBA-PD subjects);
• ongoing treatment with cholinergic drugs

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
GBA-PD; People with Parkinson's disease who are known heterozygous carriers of pathogenic GBA gene mutations.	Diagnostic test: PET scan; 3 PET scans to analyze the dopamine metabolism, acetylcholine and tau protein deposition in the brain.; Diagnostic test: neuroQWERTY; Analysis of free-text typing in a computer and/or a touch-screen device.
Asymptomatic GBA; Known heterozygous carriers/obligated carriers of pathogenic GBA gene mutations.	Diagnostic test: PET scan; 3 PET scans to analyze the dopamine metabolism, acetylcholine and tau protein deposition in the brain.; Diagnostic test: neuroQWERTY; Analysis of free-text typing in a computer and/or a touch-screen device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acetylcholinesterase activity	11C-PMP PET	baseline
Tau protein deposition	11C-PBB3 PET	baseline
Dopaminergic denervation	11C-DTBZ PET	baseline
neuroQWERTY index	Typing analysis	baseline

Collaborators and Investigators

• Sponsor: Pacific Parkinson's Research Centre
• Collaborators: University of British Columbia; Oregon Health and Science University; University of Washington; Michael J. Fox Foundation for Parkinson's Research; Simon Fraser University; Weston Brain Institute; Silverstein Foundation
• Investigators: Principal Investigator: Michele Matarazzo, MD, Pacific Parkinson's Research Centre | University of British Columbia; Principal Investigator: A. Jon Stoessl, CM, MD, FRCPC, FCAHS, Pacific Parkinson's Research Centre | University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: September 16, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Parkinson Disease; Gaucher Disease
• Other Study ID Numbers: 16451

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