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

Primary Purpose

Parkinson Disease, REM Sleep Behavior Disorder, Healthy

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

(11C)PE2I

Ioflupane

About this trial

This is an interventional other trial for Parkinson Disease focused on measuring MRI, PET Scan

Eligibility Criteria

20 Years - 100 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Hospital for Special Surgery

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Parkinson Disease - Stage 1

Parkinson Disease - Stage 2

Parkinson Disease - Stage 3

Parkinson Disease - Stage 4

REM Sleep Behavior Disorder

Healthy Controls

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT03675282

First Posted

September 5, 2018

Last Updated

January 24, 2023

Sponsor

Weill Medical College of Cornell University

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT03675282

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 14, 2018 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease, REM Sleep Behavior Disorder, Healthy

Keywords

MRI, PET Scan

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Parkinson Disease - Stage 1

Arm Type

Experimental

Arm Description

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

Arm Title

Parkinson Disease - Stage 2

Arm Type

Experimental

Arm Description

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

Arm Title

Parkinson Disease - Stage 3

Arm Type

Experimental

Arm Description

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

Arm Title

Parkinson Disease - Stage 4

Arm Type

Experimental

Arm Description

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

Arm Title

REM Sleep Behavior Disorder

Arm Type

Experimental

Arm Description

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

Arm Title

Healthy Controls

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

(11C)PE2I

Other Intervention Name(s)

PET Scan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ioflupane

Other Intervention Name(s)

DaT scan

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Sensitivity of QSM MR imaging from baseline MR imaging to 24 month MR imaging

Description

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

Time Frame

Baseline and 24 Months

Secondary Outcome Measure Information:

Title

Assess clinical changes in disease arm

Description

Time Frame

Baseline and 24 Months

Title

Assess change in PE2i PET scan or DaT scan

Description

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

Time Frame

Baseline and 24 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexander Shtilbans, MD

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital for Special Surgery

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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