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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Milton S. Hershey Medical Center
Sponsor:
Information provided by (Responsible Party):
Xuemei Huang, MD, PhD, Principle Investigator, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT01888185
First received: January 17, 2013
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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).


Condition
Parkinson's Disease (PD)
Parkinsonism
Progressive Supranuclear Palsy (PSP)
Multiple System Atrophy (MSA)

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome 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


Estimated Enrollment: 230
Study Start Date: December 2012
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Clinical patients and community volunteers

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01888185

Contacts
Contact: Raghda Clayiff, BS 717-531-0003 ext 287083 rclayiff@hmc.psu.edu
Contact: Mechelle M Lewis, PhD 717-531-0003 ext 281166 mlewis5@hmc.psu.edu

Locations
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    rclayiff@hmc.psu.edu   
Contact: Mechelle M. Lewis, PhD    717-531-0003 ext 281166    mlewis5@hmc.psu.edu   
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.         
Sponsors and Collaborators
Milton S. Hershey Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Xuemei Huang, MD, PhD, Principle Investigator, Xuemei Huang, M.D., Ph.D., Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01888185     History of Changes
Other Study ID Numbers: MSHersheyMC-40726
Study First Received: January 17, 2013
Last Updated: August 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
Parkinson's
PD
nigrostriatal
substantia nigra
MRI
DTI
FA
R2*
Parkinson's Disease Biomarkers Program
PDBP
ferritin
transferrin
Fe
iron protein
PSP
MSA

Additional relevant MeSH terms:
Multiple System Atrophy
Shy-Drager Syndrome
Parkinson Disease
Parkinsonian Disorders
Supranuclear Palsy, Progressive
Autonomic Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Hypotension
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Ocular Motility Disorders
Ophthalmoplegia
Paralysis
Primary Dysautonomias
Signs and Symptoms
Tauopathies
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014