Clinical trial NCT03675282: Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease (Stages I-IV, REM Sleep Behavior Disorder) and Controls
Official title: Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease and Controls
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
REM Sleep Behavior Disorder
Healthy
Keywords: MRI
PET Scan
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2018-09-18
Enrollment: 82
Sex: ALL
Minimum age (years): 20
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Prospective, single center study to determine whether the current R2\* iron mapping method for measuring nigral iron changes in the brain can be significantly improved by using the Quantitative Susceptibility Mapping (QSM) based iron mapping techniques with the goal of validating QSM for potential use in later clinical trials. Subjects with a diagnosis of Parkinson's Disease, Rapid Eye Movement (REM) Sleep Behavior Disorder, and Normal Volunteers who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Detailed description: This study will evaluate the rate of iron accumulation throughout different stages of the disease and compare it to controls Thus, the investigators will be able to see if iron starts to accumulate in those patients, way before motor symptoms of Parkinson disease develop. Hypothetically, an iron chelator drug could remove excessive iron from the brain and slow down process of neurodegeneration. A precise technique to measure iron in the brain and to detect small changes therefore is needed as a radiological marker of disease progression and/or therapeutic effect in clinical trials.

Eligibility criteria: Inclusion Criteria:

* 1. Idiopathic Parkinson's Disease, REM Sleep Behavior Disorder subjects without signs of Parkinsonism and normal healthy controls a. If tremor is not present, subjects must have unilateral onset and persistent asymmetry of the symptoms. b. For PD Subjects only: Age \> 30 years at time of diagnosis of PD with a maximum age of 100 years old c. Hoehn \& Yahr stage \< V (if PD)
* 2. For PD subjects only: Receiving an optimized dopaminergic regimen (i.e., either MAO-B inhibitor, a dopamine agonist and/or low doses of L-dopa, with dose change no more frequent than every 6-month in the course of the study); or medications naive
* 3. No overt anemia, iron deficiency, or other hematological disorders
* 4. Deemed healthy and able to undergo MRI and PE2i PET imaging by the Site Investigator, based on screening assessments-- medical history, physical examination 5. For Controls \& REM Sleep Behavior Disorder Subjects Only: Age 20-80; willing to undergo multiple imaging sessions 6. Signed informed consent form

Exclusion Criteria:

* 1. Patient with atypical parkinsonism (such as suspected Progressive Supranuclear Palsy, Multiple System Atrophy) and secondary parkinsonism (such as normal pressure hydrocephalus, drug-induced, or vascular parkinsonism)
* 2. Patients with uncertainty as to having classical Parkinson's disease, such as those who might have scans without evidence of dopaminergic deficits (SWEDDs)
* 3. Presence of a medical or psychiatric comorbidity that can compromise participation in the study
* 4. Patients with clinically significant depression as determined by the Beck depression score \> 15
* 5. History of exposure to typical or atypical neuroleptics or any dopamine blocking agent within 6 months prior to enrollment
* 6. Patients with psychosis/active hallucinations and memory difficulty pre-dating the onset of motor symptoms
* 7. History of brain surgery for PD
* 8. History of thyroid disease
* 9. History of stroke or cerebral vascular disease
* 10. History of drug abuse
* 11. History of repeated head injury or encephalitis
* 12. Positive dementia by DSM IV-R
* 13. Women of childbearing potential who are not surgically sterilized have to use a reliable measure of contraception and have a negative urine pregnancy test at the screening
* 14. Participation in other investigational drug trials within 30 days prior to screening
* 15. Contraindication for receiving MRI imaging such as presence of pacemakers, certain types of metallic implants, severe claustrophobia, history of reaction to contrast material, or renal insufficiency

Primary outcomes:
measure: Change in Sensitivity of QSM MR Imaging From Baseline MR Imaging to 24 Month MR Imaging
timeFrame: Baseline and 24 Months
Secondary outcomes:
measure: Assess Clinical Changes in Disease Arm
timeFrame: Baseline and 24 Months
measure: Assess Change in PE2i PET Scan or DaT Scan
timeFrame: Baseline and 24 Months
Other outcomes:
Locations:
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Alexander Shtilbans, MD
role: PRINCIPAL_INVESTIGATOR
References: