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Genotypic Influences on Network Progression in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT04228172
Recruitment Status : Recruiting
First Posted : January 14, 2020
Last Update Posted : May 7, 2021
Sponsor:
Collaborators:
Michael J. Fox Foundation for Parkinson's Research
The Silverstein Foundation for Parkinson's with GBA
Information provided by (Responsible Party):
David Eidelberg, Northwell Health

Brief Summary:
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.

Condition or disease Intervention/treatment
Parkinson's Disease Genetic: DNA/GeneticTesting Radiation: FDG PET scan Other: MRI scan Other: Clinical and neuropsychological assessments

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.

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Study Type : Observational
Estimated Enrollment : 32 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Genotypic Influences on Network Progression in Parkinson's Disease
Actual Study Start Date : February 24, 2020
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : January 1, 2023

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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

  2. 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)


Secondary Outcome Measures :
  1. 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)

  2. Change in cognitive function [ Time Frame: Baseline and 18 months later ]
    Change in cognitive function assessed with neuropsychological testing


Biospecimen Retention:   Samples With DNA
Potential subjects may undergo DNA testing for GBA and LRRK2 PD mutations. A portion of each subjects sample will be collected and processed for storage for possible use in future studies. The samples will be banked in the Center for Genomics & Human Genetics in The Boas Center Biorepository (BCB).


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
Criteria

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
  • 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).

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): NCT04228172


Contacts
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Contact: Loreta Quartarolo, BS 516-562-1168 lquartar@northwell.edu
Contact: Toni Fitzpatrick, MA 516-562-2685 tfitzpatrick@northwell.edu

Locations
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United States, New York
Feinstein Institutes for Medical Research Recruiting
Manhasset, New York, United States, 11030
Contact: Loreta Quartarolo, BS    516-562-1168    lquartar@northwell.edu   
Contact: Toni Fitzpatrick, MA    516-562-2685    tfitzpatrick@northwell.edu   
Principal Investigator: David Eidelberg, MD         
Sponsors and Collaborators
Northwell Health
Michael J. Fox Foundation for Parkinson's Research
The Silverstein Foundation for Parkinson's with GBA
Investigators
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Principal Investigator: David Eidelberg, MD Head, Center for Neurosciences
Publications:
Schindlbeck, K.A. et al., Multicenter validation of disease-related Parkinson's disease pattern with resting state fMRI. 21st International Congress of Parkinson's Disease and Movement Disorders, June 8, 2018, Vancouver, Canada
Schindlbeck, K.A. et al., Cognition-related Parkinson's disease pattern with functional MRI - Validation and clinical correlates. 62nd Congress of the German Society for Clinical Neurophysiology and Functional Imaging (DGKN), Berlin, Germany, March 15, 2018

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Responsible Party: David Eidelberg, Professor & Head, Feinstein Center for Neurosciences, Feinstein Institutes for Medical Research, Northwell Health
ClinicalTrials.gov Identifier: NCT04228172    
Other Study ID Numbers: MJFF grant 16325
First Posted: January 14, 2020    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by David Eidelberg, Northwell Health:
GBA
genetic
progression
PD
Additional relevant MeSH terms:
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Parkinson Disease
Disease Progression
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Disease Attributes
Pathologic Processes