Genotypic Influences on Network Progression in Parkinson's Disease

January 2, 2024 updated by: David Eidelberg, Northwell Health
In this longitudinal study, the investigators will follow Parkinson's disease (PD) patients with and without glucocerebrosidase (GBA) mutations. The investigators hypothesize that the rate of increase in brain network activity over time (network progression rate) is faster in patients with GBA gene mutations.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Parkinson's disease (PD) patients with mutations in the glucocerebrosidase gene (GBA) tend to have a more aggressive disease course. GBA may therefore provide a target for disease modifying therapies in mutation carriers. Using positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging to measure network progression rates in mutation carriers will allow for the assessment of the potential disease modifying effects of new anti-GBA therapies.

The investigators will also determine whether magnetic resonance imaging (MRI) network methods, which are less invasive and more broadly available than positron emission tomography (PET), produce comparable network progression measurements in individual patients. These determinations will be critical for the design of clinical trials of new disease-modifying drugs.

Study Type

Observational

Enrollment (Estimated)

32

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • New York
      • Manhasset, New York, United States, 11030
        • Recruiting
        • Feinstein Institutes for Medical Research
        • Contact:
        • Contact:
        • Principal Investigator:
          • David Eidelberg, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Study population will be recruited through local movement disorders centers in the tri-state area, prior PD studies, The Michael J. Fox Trial Finder, community outreach

Description

Inclusion Criteria:

  • Diagnosis of PD made according to United Kingdom (UK) Parkinson's Disease Society Brain Bank Criteria
  • Ability to provide written informed consent
  • Age 40-75
  • Stable dose of antiparkinsonian medication for >1 month prior to study entry

Exclusion Criteria:

  • Subjects with pathogenic mutations in LRRK2 related PD mutations (subjects with variants of uncertain significance (VUS) are eligible
  • History of known causative factors such as encephalitis or neuroleptic treatment
  • Patients with dementia (defined as Mini-Mental Status Exam score <24 or a Telephone Interview for Cognitive Status score <26)
  • Atypical parkinsonian features including oculomotor abnormalities, incontinence, ataxia, sensory loss, or pyramidal signs
  • Known structural brain lesions
  • Patients with history of stroke, head injury, high intracranial pressure or severe headaches
  • Psychiatric disorder, including a history of major depression in the past 36 months
  • Pregnant or breastfeeding women (female subjects of child-bearing potential will be screened for pregnancy before imaging).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers
Parkinson's disease subjects with GBA mutation
Genetic: DNA/GeneticTesting
Subjects will be tested for GBA and LRRK2 mutation status at baseline.
Radiation: FDG PET scan
18F-Fluoro-2-deoxy-glucose (FDG) PET scan is a nuclear medicine test that measures glucose metabolism (energy) in your brain at baseline and 18 months later.
Other: MRI scan
Magnetic Resonance Imaging (MRI) is a noninvasive scan which produces detailed pictures of the brain using a magnetic field. In addition, a special type of MRI, called resting state functional MRI (rs-fMRI), will measure and map brain activity. Conducted at baseline and 18 months later.
Other: Clinical and neuropsychological assessments
Investigator will evaluate subjects according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the standard clinical tool used to measure the severity and progression of PD. Neuropsychological evaluation will assess how one's brain functions (via pencil and paper testing), which indirectly yields information about the structural and functional integrity of the brain. Conducted at baseline and 18 months later.
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers
Parkinson's disease subjects without GBA mutation
Genetic: DNA/GeneticTesting
Subjects will be tested for GBA and LRRK2 mutation status at baseline.
Radiation: FDG PET scan
18F-Fluoro-2-deoxy-glucose (FDG) PET scan is a nuclear medicine test that measures glucose metabolism (energy) in your brain at baseline and 18 months later.
Other: MRI scan
Magnetic Resonance Imaging (MRI) is a noninvasive scan which produces detailed pictures of the brain using a magnetic field. In addition, a special type of MRI, called resting state functional MRI (rs-fMRI), will measure and map brain activity. Conducted at baseline and 18 months later.
Other: Clinical and neuropsychological assessments
Investigator will evaluate subjects according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the standard clinical tool used to measure the severity and progression of PD. Neuropsychological evaluation will assess how one's brain functions (via pencil and paper testing), which indirectly yields information about the structural and functional integrity of the brain. Conducted at baseline and 18 months later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase in PD related metabolic pattern expression
Time Frame: Baseline and 18 months later
Changes in PD related and PD cognition related pattern expression in 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET scans
Baseline and 18 months later
Increase in PD related functional pattern expression
Time Frame: Baseline and 18 months later
Changes in PD related and PD cognition related pattern expression in resting state functional magnetic resonance imaging (rs-fMRI)
Baseline and 18 months later

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in motor function
Time Frame: Baseline and 18 months later
Change in motor function assessed with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (The sum score ranges between 0-132 points. Higher scores indicate more severe impairment)
Baseline and 18 months later
Change in cognitive function
Time Frame: Baseline and 18 months later
Change in cognitive function assessed with neuropsychological testing
Baseline and 18 months later

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Collaborators

Michael J. Fox Foundation for Parkinson's Research
The Silverstein Foundation for Parkinson's with GBA

Investigators

  • Principal Investigator: David Eidelberg, MD, Head, Center for Neurosciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 24, 2020

Primary Completion (Estimated)

June 20, 2024

Study Completion (Estimated)

June 20, 2024

Study Registration Dates

First Submitted

January 7, 2020

First Submitted That Met QC Criteria

January 10, 2020

First Posted (Actual)

January 14, 2020

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MJFF grant 16325

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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