Clinical trial NCT01888185: Identifying Biomarkers of Parkinson's Disease Using Magnetic Resonance Imaging (MRI)
Official title: Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Parkinson's Disease (PD)
Parkinsonism
Progressive Supranuclear Palsy (PSP)
Multiple System Atrophy (MSA)
Keywords: Parkinson's
PD
nigrostriatal
substantia nigra
MRI
DTI
FA
R2*
Parkinson's Disease Biomarkers Program
PDBP
ferritin
transferrin
Fe
iron protein
PSP
MSA
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2013-06-27
Enrollment: 290
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Clinical patients and community volunteers

Brief summary: 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).

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 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.

Primary outcomes:
measure: Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
timeFrame: 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.
Secondary outcomes:
measure: Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes
timeFrame: Assessed at baseline visit.
measure: Iron(Fe)-related proteins in body fluids as biomarkers of PD
timeFrame: Change assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.
measure: MRI and postmortem pathological correlation
timeFrame: From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center and College of Medicine
state: Pennsylvania
Study officials:
References: