Identifying Biomarkers of Parkinson's Disease Using Magnetic Resonance Imaging (MRI)
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).
Parkinson's Disease (PD)
Progressive Supranuclear Palsy (PSP)
Multiple System Atrophy (MSA)
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease|
- Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression [ Time Frame: 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. ] [ Designated as safety issue: No ]Substantia Nigra (SN) FA and R2* values in PD subjects will be compared with control subjects and correlated with clinical and behavioral measures.
- Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes [ Time Frame: Assessed at baseline visit. ] [ Designated as safety issue: No ]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.
- Iron(Fe)-related proteins in body fluids as biomarkers of PD [ Time Frame: Change assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months. ] [ Designated as safety issue: No ]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.
- MRI and postmortem pathological correlation [ Time Frame: From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease ] [ Designated as safety issue: No ]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.
Biospecimen Retention: Samples With DNA
Whole blood, serum, plasma, white blood cells, urine, cerebral spinal fluid (CSF), tissue
|Study Start Date:||December 2012|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
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)
Age and gender-matched adults free from neurological disease
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.
|Contact: Raghda Clayiff, BS||717-531-0003 ext firstname.lastname@example.org|
|Contact: Mechelle M Lewis, PhD||717-531-0003 ext email@example.com|
|United States, Pennsylvania|
|Penn State Milton S. Hershey Medical Center and College of Medicine||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Raghda Clayiff, B.S. 717-531-0003 ext 287083 firstname.lastname@example.org|
|Contact: Mechelle M. Lewis, PhD 717-531-0003 ext 281166 email@example.com|
|Principal Investigator: Xuemei Huang, M.D., Ph.D.|
|Sub-Investigator: James Connor, Ph.D.|
|Sub-Investigator: Jennifer Baccon, M.D., Ph.D.|
|Sub-Investigator: Mechelle M Lewis, Ph.D.|
|Sub-Investigator: Guangwei Du, M.D., Ph.D.|
|Sub-Investigator: Paul Eslinger, Ph.D.|
|Sub-Investigator: Qing X Yang, Ph.D.|
|Sub-Investigator: Sangam Kanekar, M.D.|