Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 290
- 试验地点
- 1
- 主要终点
- Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
研究概览
简要总结
This study is designed to determine if magnetic resonance imaging (MRI) measures can be used to diagnose and monitor the progression of Parkinson's disease (PD) while distinguishing between PD and parkinsonisms [conditions that are PD look-a-like diseases such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA)] when combined with changes in certain proteins in body fluids that are related to iron (Fe).
详细描述
The lack of in vivo biomarker(s) reflecting Parkinson's disease (PD)-related cell loss and associated pathoetiological/physiological processes in nigrostriatal structures has hindered discovery research and limited the ability to evaluate disease-modifying therapies. Recent research has generated excitement for using DTI and R2* MRI measures as biomarker(s) for PD-related pathology in nigrostriatal pathways, but they fall short by the lack of understanding of their clinical implications and biological/pathological underpinnings. Working closely with the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson's Disease Biomarkers Program (PDBP), the proposed work will investigate multimodal MRI techniques in combination with fluid-based iron (Fe) protein profiles to serve as in vivo markers for PD-related nigrostriatal pathology that can be used as biomarkers for diagnosing PD, following its progression, and gaining mechanistic understanding of PD pathoetiology and pathophysiology.
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
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PD Subjects:
- •Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
- •MMSE score of 15 or greater unless a legal representative is present.
- •Idiopathic PD according to published criteria.
- •History of adequate response to dopaminergic therapy.
- •History of asymmetrical symptom onset
- •MSA Subjects:
- •Older than 30 yrs.
- •Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
- •MMSE score of 15 or greater unless a legal representative is present.
- •MSA according to published criteria.
- •History of autonomic & urinary dysfunction and/or severe cerebellar ataxia.
- •PSP Subjects:
- •Older than 40 yrs.
- •Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
- •PSP according to published criteria.
- •Vertical gaze palsy and/or slow vertical gaze/postural instability during first year of diagnosis.
- •MMSE score of 15 or greater unless a legal representative is present
- •Older than 21 yrs.
- •Able and willing to sign the consent form.
- •MMSE greater than 24.
排除标准
- •PD Subjects:
- •Unable or does not have a legal representative/unwilling to provide consent.
- •Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- •History of cerebrovascular diseases or other neurological disorders.
- •Major medical problems such as renal or liver failure.
- •Unstable, non-PD-related medical conditions.
- •MMSE score less than 15 unless a legal representative is present
- •Use of anticoagulant medications.
- •Signs of dementia.
- •MSA Subjects:
- •Unable or does not have a legal representative /unwilling to provide consent.
- •Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- •History of cerebrovascular diseases or other neurological disorders.
- •Major medical problems such as renal or liver failure.
- •Unstable, non-MSA-related medical conditions.
- •MMSE score less than 15 unless a legal representative is present
- •Use of anticoagulant medications.
- •Signs of dementia.
- •PSP Subjects:
- •Unable or does not have a legal representative /unwilling to provide consent.
- •Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- •History of cerebrovascular diseases or other neurological disorders.
- •Major medical problems such as renal or liver failure.
- •Unstable, non-PSP-related medical conditions.
- •MMSE score less than 15 unless a legal representative is present
- •Use of anticoagulant medications.
- •Signs of dementia.
- •Unable/unwilling to provide consent.
- •Evidence of severe memory impairment or signs of dementia (MMSE < 24).
- •Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- •History of cerebrovascular diseases or other neurological disorders.
- •Major medical problems such as renal or liver failure.
- •Unstable medical conditions.
- •Use of anticoagulant medications.
- •Signs of dementia.
结局指标
主要结局
Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
时间窗: Change in roles of FA and R2* assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.
Substantia Nigra (SN) FA and R2\* values in PD subjects will be compared with control subjects and correlated with clinical and behavioral measures.
次要结局
- Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes(Assessed at baseline visit.)
- Iron(Fe)-related proteins in body fluids as biomarkers of PD(Change assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.)
- MRI and postmortem pathological correlation(From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease)
研究者
Xuemei Huang, MD, PhD
Xuemei Huang, M.D., Ph.D.
Milton S. Hershey Medical Center