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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03675282
• Other study ID #: 1711018740
• Secondary ID: 1R01NS095562-01A
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 14, 2018
• Est. completion date: April 30, 2024

Study information

• Verified date: March 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Mental Disorders
• Parkinson Disease
• REM Sleep Behavior Disorder

Intervention

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

Locations

Country	Name	City	State
United States	Hospital for Special Surgery	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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