Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease (Stages I-IV, REM Sleep Behavior Disorder) and Controls

Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease and Controls

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy; Parkinson Disease; REM Sleep Behavior Disorder
• Intervention / Treatment: Drug: (11C)PE2I; Drug: Ioflupane

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parkinson Disease - Stage 1; MRI Brain at Baseline and 24 Months PE2i PET Scan or DaT Scan at Baseline and 24 Months Office Visit at Baseline and 24 Months	Drug: (11C)PE2I; Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits; Other Names: PET Scan; Drug: Ioflupane; Subjects will receive a DaT scan at baseline and 24 month visits if they don't receive a PE2I PET scan at baseline and 24 month visits; Other Names: DaT scan
Experimental: Parkinson Disease - Stage 2; MRI Brain at Baseline and 24 Months PE2i PET Scan or DaT Scan at Baseline and 24 Months Office Visit at Baseline and 24 Months	Drug: (11C)PE2I; Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits; Other Names: PET Scan; Drug: Ioflupane; Subjects will receive a DaT scan at baseline and 24 month visits if they don't receive a PE2I PET scan at baseline and 24 month visits; Other Names: DaT scan
Experimental: Parkinson Disease - Stage 3; MRI Brain at Baseline and 24 Months PE2i PET Scan or DaT Scan at Baseline and 24 Months Office Visit at Baseline and 24 Months	Drug: (11C)PE2I; Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits; Other Names: PET Scan; Drug: Ioflupane; Subjects will receive a DaT scan at baseline and 24 month visits if they don't receive a PE2I PET scan at baseline and 24 month visits; Other Names: DaT scan
Experimental: Parkinson Disease - Stage 4; MRI Brain at Baseline and 24 Months PE2i PET Scan or DaT Scan at Baseline and 24 Months Office Visit at Baseline and 24 Months	Drug: (11C)PE2I; Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits; Other Names: PET Scan; Drug: Ioflupane; Subjects will receive a DaT scan at baseline and 24 month visits if they don't receive a PE2I PET scan at baseline and 24 month visits; Other Names: DaT scan
Experimental: REM Sleep Behavior Disorder; MRI Brain at Baseline and 24 Months PE2i PET Scan or DaT Scan at Baseline and 24 Months Office Visit at Baseline and 24 Months	Drug: (11C)PE2I; Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits; Other Names: PET Scan; Drug: Ioflupane; Subjects will receive a DaT scan at baseline and 24 month visits if they don't receive a PE2I PET scan at baseline and 24 month visits; Other Names: DaT scan
Experimental: Healthy Controls; MRI Brain at Baseline and 24 Months PE2i PET Scan or DaT Scan at Baseline and 24 Months Office Visit at Baseline and 24 Months	Drug: (11C)PE2I; Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits; Other Names: PET Scan; Drug: Ioflupane; Subjects will receive a DaT scan at baseline and 24 month visits if they don't receive a PE2I PET scan at baseline and 24 month visits; Other Names: DaT scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sensitivity of QSM MR imaging from baseline MR imaging to 24 month MR imaging	Change in Sensitivity of QSM MR imaging as compared to R2* from baseline MR imaging to 24 month MR imaging, as measured by Radiology reader agreements	Baseline and 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess clinical changes in disease arm	Assess clinical changes in disease arm, as measured by changes in unified Parkinson's disease rating scale (UPDRS) scale assessments at baseline and 24 Month visits. The UPDRS is used to follow the longitudinal course of Parkinson's disease. The UPDRS is made up of 42 questions grouped into 4 sections: Part I: evaluation of mentation, behavior, and mood Part II: self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food Part III: clinician-scored monitored motor evaluation Part IV: complications of therapy score for part I range is: 0-16 score for part II range is:0- 52 score for part III range is: 0-108 score for part IV range is: 0-23 The higher the score value, the worse symptoms are.	Baseline and 24 Months
Assess change in PE2i PET scan or DaT scan	Assess changes in dopamine depletion as measured by the baseline PE2i PET scan or DaT scan compared to the 24 month PE2i PET scan or DaT scan	Baseline and 24 Months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Alexander Shtilbans, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2018
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MRI; PET Scan
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parasomnias; REM Sleep Parasomnias; Parkinson Disease; Mental Disorders; REM Sleep Behavior Disorder
• Other Study ID Numbers: 1711018740; 1R01NS095562-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No