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

NCT ID: NCT03675282

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-14
• Study Completion Date: 2024-04-23

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.

Conditions

Parkinson Disease; REM Sleep Behavior Disorder; Healthy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

(11C)PE2I

Intervention Type: DRUG

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Ioflupane

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

(11C)PE2I

Intervention Type: DRUG

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Ioflupane

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

(11C)PE2I

Intervention Type: DRUG

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Ioflupane

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

(11C)PE2I

Intervention Type: DRUG

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Ioflupane

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

(11C)PE2I

Intervention Type: DRUG

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Ioflupane

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

(11C)PE2I

Intervention Type: DRUG

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Ioflupane

Intervention Type: DRUG

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

Interventions

(11C)PE2I

Subjects will received (11C)PE2I PET Scans at Baseline and 24 Month Visits

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

PET Scan; DaT scan

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexander Shtilbans, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Hospital for Special Surgery

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01NS095562-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1711018740

Identifier Type: -

Identifier Source: org_study_id