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Identifying Biomarkers of Parkinson's Disease Using Magnetic Resonance Imaging (MRI)

2020年1月2日 更新者:Xuemei Huang, MD, PhD、Milton S. Hershey Medical Center

Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease

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).

研究概览

详细说明

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.

研究类型

观察性的

注册 (实际的)

290

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Pennsylvania
      • Hershey、Pennsylvania、美国、17033
        • Penn State Milton S. Hershey Medical Center and College of Medicine

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

21年 至 90年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

取样方法

非概率样本

研究人群

Clinical patients and community volunteers

描述

Inclusion Criteria:

PD Subjects:

  1. 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.
  2. MMSE score of 15 or greater unless a legal representative is present.
  3. Idiopathic PD according to published criteria.
  4. History of adequate response to dopaminergic therapy.
  5. History of asymmetrical symptom onset

MSA Subjects:

  1. Older than 30 yrs.
  2. 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.
  3. MMSE score of 15 or greater unless a legal representative is present.
  4. MSA according to published criteria.
  5. History of autonomic & urinary dysfunction and/or severe cerebellar ataxia.

PSP Subjects:

  1. Older than 40 yrs.
  2. 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.
  3. PSP according to published criteria.
  4. Vertical gaze palsy and/or slow vertical gaze/postural instability during first year of diagnosis.
  5. MMSE score of 15 or greater unless a legal representative is present

Controls:

  1. Older than 21 yrs.
  2. Able and willing to sign the consent form.
  3. MMSE greater than 24.

Exclusion Criteria:

PD Subjects:

  1. Unable or does not have a legal representative/unwilling to provide consent.
  2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  3. History of cerebrovascular diseases or other neurological disorders.
  4. Major medical problems such as renal or liver failure.
  5. Unstable, non-PD-related medical conditions.
  6. MMSE score less than 15 unless a legal representative is present
  7. Use of anticoagulant medications.
  8. Signs of dementia.

MSA Subjects:

  1. Unable or does not have a legal representative /unwilling to provide consent.
  2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  3. History of cerebrovascular diseases or other neurological disorders.
  4. Major medical problems such as renal or liver failure.
  5. Unstable, non-MSA-related medical conditions.
  6. MMSE score less than 15 unless a legal representative is present
  7. Use of anticoagulant medications.
  8. Signs of dementia.

PSP Subjects:

  1. Unable or does not have a legal representative /unwilling to provide consent.
  2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  3. History of cerebrovascular diseases or other neurological disorders.
  4. Major medical problems such as renal or liver failure.
  5. Unstable, non-PSP-related medical conditions.
  6. MMSE score less than 15 unless a legal representative is present
  7. Use of anticoagulant medications.
  8. Signs of dementia.

Controls:

  1. Unable/unwilling to provide consent.
  2. Evidence of severe memory impairment or signs of dementia (MMSE < 24).
  3. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  4. History of cerebrovascular diseases or other neurological disorders.
  5. Major medical problems such as renal or liver failure.
  6. Unstable medical conditions.
  7. Use of anticoagulant medications.
  8. Signs of dementia.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

队列和干预

团体/队列
Parkinson's Disease (PD)
Patients with a clinical diagnosis of PD (in various stages)
Progressive supranuclear palsy (PSP)
Patients with a clinical diagnosis of PSP (in various stages)
Multiple system atrophy (MSA)
Patients with a clinical diagnosis of MSA (in various stages)
Controls
Age and gender-matched adults free from neurological disease

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
大体时间: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.
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.

次要结果测量

结果测量
措施说明
大体时间
Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes
大体时间:Assessed at baseline visit.
DTI and R2* measures in both SN and striatal structures in PD, PSP, MSA and control subjects will be compared to assess sensitivity and specificity of individual and combined MRI measures in diagnosing PD.
Assessed at baseline visit.
Iron(Fe)-related proteins in body fluids as biomarkers of PD
大体时间:Change assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.
The protein profile in blood, urine, and cerebral spinal fluid (CSF), and their relationships to clinical and MRI measure will be interrogated with the focus being on Fe-related proteins such as hepcidin, ferritin, and transferrin.
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
大体时间:From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease
Postmortem brain analysis on patients who succumb to their disease during the study will be performed in order to inform the relationship of the biomarkers to clinical diagnosis (PD, PSP, MSA) and clinical milestones as well as to inform the pathological underpinnings of the R2* and DTI measures. In addition to standard postmortem diagnostic tests (alpha-synuclein, beta-amyloid, tau, and ubiquitin), total Fe staining, ferritin, hepcidin, tyrosine hydroxylase positive neurons, myelin and glial derived growth factors (glial cell markers) will be assessed in nigrostriatal structures in order to correlate these levels with MRI measures.
From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2012年12月1日

初级完成 (实际的)

2019年12月1日

研究完成 (实际的)

2019年12月31日

研究注册日期

首次提交

2013年1月17日

首先提交符合 QC 标准的

2013年6月25日

首次发布 (估计)

2013年6月27日

研究记录更新

最后更新发布 (实际的)

2020年1月3日

上次提交的符合 QC 标准的更新

2020年1月2日

最后验证

2020年1月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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