Genotypic Influences on Network Progression in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Increase in PD related metabolic pattern expression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers
Parkinson's disease subjects with GBA mutation
干预措施: DNA/GeneticTesting (Genetic)
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers
Parkinson's disease subjects with GBA mutation
干预措施: FDG PET scan (Radiation)
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers
Parkinson's disease subjects with GBA mutation
干预措施: MRI scan (Other)
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers
Parkinson's disease subjects with GBA mutation
干预措施: Clinical and neuropsychological assessments (Other)
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers
Parkinson's disease subjects without GBA mutation
干预措施: DNA/GeneticTesting (Genetic)
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers
Parkinson's disease subjects without GBA mutation
干预措施: FDG PET scan (Radiation)
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers
Parkinson's disease subjects without GBA mutation
干预措施: MRI scan (Other)
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers
Parkinson's disease subjects without GBA mutation
干预措施: Clinical and neuropsychological assessments (Other)
结局指标
主要结局
Increase in PD related metabolic pattern expression
时间窗: 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
时间窗: Baseline and 18 months later
Changes in PD related and PD cognition related pattern expression in resting state functional magnetic resonance imaging (rs-fMRI)
次要结局
- Change in motor function(Baseline and 18 months later)
- Change in cognitive function(Baseline and 18 months later)
研究者
David Eidelberg
Professor & Head, Feinstein Center for Neurosciences, Feinstein Institutes for Medical Research
Northwell Health