Biomarkers of Risk of Parkinson Disease

NCT00775853 | Completed FDA Drug

• 2 other identifiers: 09001009-N-0010
• Study Type: observational
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

This study (https://pdrisk.ninds.nih.gov) will determine if people who have risk factors for Parkinson disease (PD) have biomarkers (objective ways to measure a disease process) that show that the disease process is actually going on, and if people who have abnormal biomarkers go on to develop PD during several years of follow-up. Biomarkers of Parkinson disease (PD) might identify people who are healthy now but may develop the disease later in life. Healthy volunteers and people who have certain risk factors for developing PD who are between 18 and 70 years of age may be eligible for this study. People with the following risk factors are included:

• Family history of PD
• Loss of sense of smell
• Fall in blood pressure when standing up
• REM behavior disorder (a type of sleep disturbance) Participants undergo the following tests and procedures:
• Screening examination
• Medical and neurological history and physical examination
• Tests or rating scales for movement, sense of smell, mood, attention, fatigue, pain, and thinking.
• Measurement of blood pressure and pulse rate while lying down and then standing up
• Blood draw for genetic testing
• Inpatient testing at the NIH Clinical Center for 2-3 days, including:
• Measurements while blowing against a resistance
• Measurements of blood pressure and pulse rate
• Blood draws for levels of various chemicals
• PET and MRI scanning
• Lumbar puncture (spinal tap)
• Electrocardiogram
• Skin electrical conduction test (test of sweat production)
• Skin and core temperature measurements
• Transcranial ultrasound (sound-wave test of the head)
• Follow-up testing (up to five visits in 18-month intervals) to repeat some of the tests listed above, excluding the genetic testing and spinal tap

Conditions

Parkinson Disease; Autonomic Nervous System Diseases; Pure Autonomic Failure

Keywords

Biomarkers; Catecholamines; 18F-Fluoro-L-dopa; Fluorodopamine; Parkinson's Disease; Natural History; Parkinson Disease; PD

Outcome Measures

Primary Outcomes (1)

• Parkinson Disease Diagnosed

  The primary objective of this study is to determine whether among people at increased statistical risk for developing PD those with clinical laboratory biomarkers of central or cardiac catecholamine deficiency are diagnosed with PD during follow-up, whereas those without evidence of central or peripheral catecholamine deficiency are not diagnosed with PD during follow-up.

  annually within 7.5 years

Study Arms (1)

Individuals at risk for developing PD

Individuals who may be at risk for developing PD because of genetic risk, olfactory dysfunction, symptomatic rapid eye movement sleep behavior disorder, or orthostatic hypotension

Drug: 6-[18F]Fluorodopamine; Drug: 6-[18F]Fluorodopa; Drug: 13N-Ammonia

Interventions

6-[18F]Fluorodopamine DRUG

Individuals at risk for developing PD

6-[18F]Fluorodopa DRUG

Individuals at risk for developing PD

13N-Ammonia DRUG

Individuals at risk for developing PD

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The subjects are individuals who may be at risk for developing PD, because of (a) genetic risk i.e., a family history of PD or genotypic abnormalities known to be associated statistically with PD; (b) olfactory dysfunction i.e., decreased ability to distinguish among odors; (c) symptomatic rapid eye movement (REM) sleep behavior disorder (RBD); or (d) orthostatic hypotension.

You may qualify if:

• Individuals who report at least 3 of the following 4 risk factors at the protocol-specific website may be invited to the Screening Examination. All subjects must have ability to provide their own consent for participation in the study. Otherwise eligible candidate participants who are taking medications that would interfere with the scientific results may be included, if (1) the medications are held temporarily or safely substituted for, and (2) the medications are held while the participants are inpatients. The prescribing physician will be contacted, with the participant's permission, if withholding or substituting medication is considered.
• Genetic Risk: A positive family history (one immediate or more than one non-immediate family member with PD) or positive genetic testing (e.g., LRRK2, alpha-synuclein, glucocerebrosidase) satisfies this risk factor criterion.
• Olfactory Dysfunction: Olfactory dysfunction reported at the protocol-specific website satisfies this criterion. This may be confirmed by the UPSIT sent by mail prior to the Screening Examination.
• REM Behavior Disorder (RBD): To satisfy this risk factor criterion, the individual must have movements of the body or limbs associated with dreaming and at least one of the following: potentially harmful sleep behavior, dreams that appear to be acted out, and sleep behavior that disrupts sleep continuity.
• Orthostatic Hypotension (OH): To satisfy this risk factor criterion, the individual reports symptoms of orthostatic hypotension or having orthostatic hypotension at the protocol-specific website. This may be confirmed by orthostatic vital signs prior to the Screening Examination.

You may not qualify if:

• Age: People younger than 18 years old or older than 70 years old are excluded.
• Risk: A candidate subject is excluded if, in the judgment of the Principal Investigator, Protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject may be excluded from the study if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit. An example of such risk is inability to travel safely to the NIH Clinical Center, in Bethesda, Maryland, due to a neurological disorder associated with frequent falls.
• Disqualifying Conditions: A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are insulin-dependent diabetes, hepatic or renal failure, symptomatic congestive heart failure, severe anemia, psychosis, ventricular arrhythmias, and symptomatic coronary heart disease.
• Unable to Provide Consent: Persons who are unable to provide their own consent (e.g., due to dementia) are excluded.
• MRI: Persons who are unable to undergo MRI safely, due to implanted metal, are excluded from the MRI procedure.
• Safe Travel: A candidate participant is excluded if the person is unable to travel safely to the NIH Clinical Center, in Bethesda, Maryland, such as due to a neurological disorder associated with frequent falls.
• Herbal Medicines and Dietary Supplements: If a subject wishes to continue herbal medicines or dietary supplements while on study, but a search of the available medical identifies drug effects that are known or expected to interfere with the experimental results, then the subject may be excluded, at the discretion of Principal Investigator
• Practical Limitations: People in whom we feel it would be difficult to insert a catheter into a vein may be excluded. People who are not expected clinically to tolerate lying still supine during the testing will be excluded.
• Pregnancy: Pregnant or lactating women are excluded

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 (1)

• Goldstein DS, Holmes C, Sullivan P, Lopez G, Gelsomino J, Moore S, Isonaka R, Wu T, Sharabi Y. Cardiac noradrenergic deficiency revealed by 18F-dopamine positron emission tomography identifies preclinical central Lewy body diseases. J Clin Invest. 2024 Jan 2;134(1):e172460. doi: 10.1172/JCI172460.

  PMID: 37883190 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Parkinson Disease; Autonomic Nervous System Diseases; Pure Autonomic Failure

Interventions

6-fluorodopamine

Condition Hierarchy (Ancestors)

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

Study Officials

• David S Goldstein, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 17, 2008
• First Posted: October 20, 2008
• Study Start: May 27, 2009
• Primary Completion: January 11, 2023
• Study Completion: January 11, 2023
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)