Genotypic Influences on Network Progression in Parkinson's Disease

Active, not recruiting

• Conditions: Parkinson's Disease
• Interventions: Genetic: DNA/GeneticTesting; Radiation: FDG PET scan; Other: MRI scan; Other: Clinical and neuropsychological assessments

• Registration Number: NCT04228172
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2020-01-07
• Study First Submitted QC: 2020-01-10
• Study First Posted: 2020-01-14
• Study Start: 2020-02-24
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-17
• Last Update Posted: 2024-12-20
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers	FDG PET scan	Parkinson's disease subjects with GBA mutation
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers	Clinical and neuropsychological assessments	Parkinson's disease subjects with GBA mutation
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers	Clinical and neuropsychological assessments	Parkinson's disease subjects without GBA mutation
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers	MRI scan	Parkinson's disease subjects with GBA mutation
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers	FDG PET scan	Parkinson's disease subjects without GBA mutation
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers	MRI scan	Parkinson's disease subjects without GBA mutation
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers	DNA/GeneticTesting	Parkinson's disease subjects with GBA mutation
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers	DNA/GeneticTesting	Parkinson's disease subjects without GBA mutation

Primary Outcome Measures

Name	Time	Method
Increase in PD related metabolic pattern expression	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
Increase in PD related functional pattern expression	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

Name	Time	Method
Change in motor function	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)
Change in cognitive function	Baseline and 18 months later	Change in cognitive function assessed with neuropsychological testing

Trial Locations

Locations (1)

Feinstein Institutes for Medical Research; 🇺🇸 Manhasset, New York, United States