Imaging Biomarkers in Parkinson s Disease

NCT01496599 | Completed

• 2 other identifiers: 12003112-N-0031
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Parkinson s disease (PD) causes slow movement, stiffness, and tremor. It results from the loss of a brain chemical called dopamine. PD gets worse over time, but researchers do not fully understand why the brain cells that produce dopamine stop working or die in people with PD. This study will use different ways of imaging the brain and brain chemicals to look at PD. It will compare brain imaging in people who definitely have PD to people who might have PD and to people without signs of PD. It will provide more information how the brain in people with PD changes over time. Objectives: \- To understand the changes that occur in the brains of people with Parkinson s disease. Eligibility:

• Individuals at least 18 years of age who have definite or possible Parkinson s disease.
• Healthy volunteers at least 18 years of age. Design:
• Participants will have a screening visit with a physical exam and medical history.
• Participants will visit the National Institutes of Health Clinical Center every 18 month or 3 years for up to 9 years. There will be up to 6 total visits. Most visits will last 5 to 6 hours a day for 1 to 3 days. Some or all of the following tests will be performed at each visit:
• Magnetic resonance imaging to take pictures of the brain. Some of these tests will be done at rest. Others will require participants to perform an activity during the scan.
• Medication withdrawal for 12 hours overnight for people taking PD medications. This may be done before some scans. Participants who feel unwell when they stop taking medications will be allowed to start taking them again.
• Participants will continue with the follow up visits until the end of the study.

Conditions

Parkinson Disease

Keywords

Brain Imaging; Parkinson's Disease; Parkinsonism; Natural History; Parkinson Disease; PD; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Using MRI, we will measure signal intensities of iron-rich structures using T2 sequences and calculate phase shift values in these structures with susceptibility weighted sequences. We will also measure clinical symptom severity with the UPDRS s...

  -Structural MRI (SWI images): The primary outcome measure is the difference in susceptibility changes in iron-rich structures (ie. The SN, red nucleus, striatum) across groups and within groups over time.-Clinical presentation: We will evaluate how the prodromal symptoms influence the progression to clinical PD.

  10 years

Secondary Outcomes (3)

• Structural MR (morphometry and diffusion analyses)

  10 years

• fMRI

  10 years

• MRS

  10 years

Study Arms (3)

Healthy Volunteers

Subjects without PD diagnosis

Parkinsons Disease subjects

Subjects fitting the MSD Clinical Diagnostic Criteria for PD

Prodromal Parkinson disease

Subjects fitting the MDS prodromal criteria for PD

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Part 1 (Case-control study): We will study 30 patients with well-defined PD, as defined by the UK Parkinson s Society Brain Bank diagnostic criteria (Hughes et al., 1992, Olanow et al., 2009, Defer et al., 1999). We will also study 15 age-matched healthy volunteers (HVs) as controls. Part 2 (Longitudinal study): We will continue to study subjects from Part 1 periodically over the following 9 years. We will also study 30 subjects with early parkinsonism (EP). EP subjects are defined as individuals who have experienced at least one but fewer than 3 of the cardinal symptoms of PD at the time of enrollment.

You may qualify if:

• For all subjects:
• Age 18 or older.
• Subjects must fulfill either the clinically defined PD, prodromal PD or not having any of the red flags following the MDS criteria for PD.
• Able to give informed consent or, if there is evidence of cognitive decline, able to appoint a durable power of attorney (DPA) who can give informed consent.

You may not qualify if:

• More than 7 alcoholic drinks a week for females or 14 alcoholic drinks a week for males.
• History of a neurologic disorder such as a brain tumor, stroke, central nervous system infection, multiple sclerosis, a movement disorder other than the ones under study, epilepsy or a history of seizures or any abnormal or focal finding on neurological exam other than that associated with those studied in this protocol.
• History of any head injury with loss of consciousness
• Pregnancy or positive pregnancy test before the research procedure due to the risks associated with MRI scans. This would exclude subjects from participating in the protocol at that time.
• Inability to lie flat on the back for up to 2 hours
• Claustrophobia or a feeling of discomfort from being in small, enclosed spaces.
• Surgically or traumatically implanted metallic foreign bodies, such as pacemakers, implanted medical pumps, implanted hearing aids, metal plates in the skull or metal implants in the skull or eyes (other than dental fillings) that may be physically hazardous during an MRI, or might distort the images.
• Ablative surgery or implanted electrodes and generator for deep brain stimulation
• Use of the following therapies which may affect mitochondrial function: Coenzyme Q10, vitamin E, vitamin C, anti-retroviral drugs, chemotherapeutic agents, anti-epileptics agents or antibiotics. (Use ofthese substances will prevent getting MRS scan only).
• Have uncontrolled head movements that may impair image data collection

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010 Jan 26;8(1):e1000298. doi: 10.1371/journal.pbio.1000298.

  PMID: 20126261 BACKGROUND

• Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009 May 26;72(21 Suppl 4):S1-136. doi: 10.1212/WNL.0b013e3181a1d44c.

  PMID: 19470958 BACKGROUND

• Schapira AH. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol. 2008 Jan;7(1):97-109. doi: 10.1016/S1474-4422(07)70327-7.

  PMID: 18093566 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Silvina G Horovitz, Ph.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2011
• First Posted: December 21, 2011
• Study Start: January 24, 2012
• Last Updated: April 1, 2026

Record last verified: 2026-02-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Starting 1 year after publication.
• Access Criteria: IPD will be shared with qualified investigators, if allowed by IRB@@@@@@Any request for data sharing will be first reviewed by the protocol PI. @@@@@@The request must include the proposed use of the data. When requested data has IRB approval for data sharing, and the PI considers it a reasonable request, a memo of understanding will be signed by the parts, including the allowed use for the data. This will be done in consultation with the office of Tech Transfer.

Locations

US (1)