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The GBA Multimodal Study in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT04101968
Recruitment Status : Recruiting
First Posted : September 24, 2019
Last Update Posted : September 24, 2019
Sponsor:
Collaborators:
University of British Columbia
University of Washington
Oregon Health and Science University
Simon Fraser University
Michael J. Fox Foundation for Parkinson's Research
Silverstein Foundation
Weston Brain Institute
Information provided by (Responsible Party):
Pacific Parkinson's Research Centre

Brief Summary:
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.

Condition or disease Intervention/treatment
Parkinson Disease GBA Gene Mutation Gaucher Disease 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.


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Study Type : Observational
Estimated Enrollment : 25 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Multimodal Molecular Imaging and Biometric Analysis in GBA-PD and Asymptomatic GBA-mutation Carriers
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2021


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.




Primary Outcome Measures :
  1. Acetylcholinesterase activity [ Time Frame: baseline ]
    11C-PMP PET

  2. Tau protein deposition [ Time Frame: baseline ]
    11C-PBB3 PET

  3. Dopaminergic denervation [ Time Frame: baseline ]
    11C-DTBZ PET

  4. neuroQWERTY index [ Time Frame: baseline ]
    Typing analysis


Biospecimen Retention:   Samples With DNA
Blood sample


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
People with a known pathogenic GBA gene mutation with or without PD.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04101968


Contacts
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Contact: Michele Matarazzo, MD +1-604-822-7764 michele.matarazzo@ubc.ca

Locations
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United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Matthew Brodsky, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98108-1595
Principal Investigator: Cyrus P Zabetian, MD, MS         
Canada, British Columbia
Pacific Parkinson's Research Centre | University of British Columbia Recruiting
Vancouver, British Columbia, Canada
Contact: Nicole Neilson    +1-604-822-7705    nicole.neilson@ubc.ca   
Contact: Jess McKenzie    +1-604-822-7764    jess.mckenzie@ubc.ca   
Sponsors and Collaborators
Pacific Parkinson's Research Centre
University of British Columbia
University of Washington
Oregon Health and Science University
Simon Fraser University
Michael J. Fox Foundation for Parkinson's Research
Silverstein Foundation
Weston Brain Institute
Investigators
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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

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Responsible Party: Pacific Parkinson's Research Centre
ClinicalTrials.gov Identifier: NCT04101968     History of Changes
Other Study ID Numbers: 16451
First Posted: September 24, 2019    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pacific Parkinson's Research Centre:
Parkinson
Additional relevant MeSH terms:
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Parkinson Disease
Gaucher Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders