Biomarkers of Risk of Parkinson Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00775853
Recruitment Status : Active, not recruiting
First Posted : October 20, 2008
Last Update Posted : July 10, 2018
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This study ( 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

Condition or disease
Parkinson Disease Autonomic Nervous System Diseases Pure Autonomic Failure

Detailed Description:

Objective: This Protocol is to test whether individuals with statistical risk factors for Parkinson disease (PD) have abnormal values for biomarkers of central or peripheral catecholaminergic innervation and whether at-risk individuals with positive biomarkers develop PD within up to 7.5 years of follow-up.

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. A total of 200 at-risk subjects undergo catecholaminergic biomarker testing by (18)F-DOPA brain and (18)F-dopamine cardiac scanning. At-risk subjects with positive biomarkers are compared to at-risk subjects without positive biomarkers, in terms of development of PD during follow-up. Up to 20 control subjects are included, to add to a database of normal values for catecholaminergic biomarkers.

Design: The study includes four phases recruitment, screening, laboratory biomarkers testing, and follow-up. Recruitment is by advertisement and a web site questionnaire of self-reported risk. A screening examination is done at the NIH Clinical Center, to confirm risk status. Based on the screening examination results, subjects undergo inpatient clinical laboratory testing, to identify central and peripheral catecholaminergic denervation. In the follow-up phase, subjects are re-tested as inpatients approximately every 18 months for a total of up to 5 re-evaluations (90 months, or 7.5 years), to detect the onset of the characteristic movement disorder in PD and follow the status of catecholaminergic innervation.

Outcome Measures:

Primary: Diagnosis of PD by a Board-certified neurologist who is blinded to risk factor status and the results of catecholaminergic biomarkers testing. If PD diagnosed, time to diagnosis.

Secondary: UPDRS; (18)F-DOPA brain scanning, (18)F-dopamine cardiac scanning; CSF and plasma neurochemicals; neuropsychological rating scales; autonomic function testing, retrospective CSF proteomics; retrospective DNA analyses.

Study Type : Observational
Actual Enrollment : 88 participants
Time Perspective: Prospective
Official Title: Biomarkers of Risk of Parkinson Disease
Study Start Date : October 16, 2008

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Diagnosis of Parkinson disease (PD) based on the characteristic movement disorder in PD, confirmed by Unified Parkinson Disease Rating Scale (UPDRS).

Secondary Outcome Measures :
  1. Brain 6-[18F]fluorodopa-derived radioactivity; cardiac 6-[18F]fluorodopamine-derived radioactivity; CSF neurochemicals; olfactory testing; autonomic function tests; neurobehavioral rating scales.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

  1. 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.
  2. 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.
  3. 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.
  4. 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.


  1. Age: People younger than 18 years old or older than 70 years old are excluded.
  2. 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.
  3. 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.
  4. Medications: A candidate subject is excluded if clinical considerations require continued treatment with a drug likely to interfere with the scientific results. Chronic, ongoing use of drugs such as tricyclic antidepressants that affect the clinical laboratory results exclude candidate subjects. People with known or suspected allergy or hypersensitivity to any test drug are excluded. Candidate subjects are not to discontinue any medications before discussion with the Principal Investigator, Research Nurse, Nurse Practitioner, or Clinical Fellow. Temporary discontinuation of serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor), duloxetine (Cymbalta), or des-venlafaxine (Pristiq) can result in rapid rebound of depression or anxiety, and so treatment with SNRIs is exclusionary.
  5. 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
  6. 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.
  7. Pregnancy: Pregnant or lactating women are excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00775853

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: David S Goldstein, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
Publications: Identifier: NCT00775853     History of Changes
Other Study ID Numbers: 090010
First Posted: October 20, 2008    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: February 7, 2018

Studies a U.S. FDA-regulated Drug Product: No

Keywords provided by National Institutes of Health Clinical Center (CC):
Parkinson's Disease
Parkinson Disease

Additional relevant MeSH terms:
Parkinson Disease
Nervous System Diseases
Pure Autonomic Failure
Autonomic Nervous System Diseases
Primary Dysautonomias
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases