Biomarkers of Risk of Parkinson Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00775853
First received: October 17, 2008
Last updated: July 12, 2014
Last verified: April 2014
  Purpose

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

Condition
Parkinson Disease
Autonomic Nervous System Diseases
Pure Autonomic Failure

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Biomarkers of Risk of Parkinson Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

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

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

Estimated Enrollment: 220
Study Start Date: October 2008
Detailed Description:

Objective: This Protocol is to test whether individuals with putative 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 6-[18F]fluorodopa brain and 6-[18F]fluorodopamine 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 clinical laboratory testing, to identify central and peripheral catecholaminergic denervation. In the follow-up phase, subjects are re-tested approximately every 18 months for a total of up to 5 re-evaluations (90 months, or 7.5 years), to detect 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; 6-[18F]fluorodopa brain scanning, 6-[18F]fluorodopamine cardiac scanning; CSF and plasma neurochemicals; neuropsychological rating scales; autonomic function testing; retrospective CSF proteomics; retrospective DNA analyses.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Individuals with one or more of the following characteristics will be considered to be at risk and eligible for entering the Screening Examination phase. Priority will go to those with multiple risk factors. Subjects with at least 3 of the 4 risk factors will be invited to the Screening Examination. Control subjects will have none of these characteristics:

  1. Genetic risk is assessed at the time of the Screening Examination in two ways by creation of a pedigree and by genotyping. The pedigree shows diagrammatically the family history with respect to Parkinson disease. Genotyping is by DNA extraction and analysis for mutations of the LRRK2 or the alpha-synuclein gene or for alpha-synuclein gene replication. Either a positive family history (one or more immediate family members with PD) or positive DNA test results (LRRK2 or alpha-synuclein) satisfy the risk factor criterion for genetic risk. Other DNA analyses may be done subsequently; however, those results will not be considered relevant to genetic risk at the time of entry.
  2. Olfactory Dysfunction is identified by the UPSIT. Decreased olfactory function, as indicated by less than a normal score, satisfies this risk factor criterion. In the event of a medical history indicating a secondary cause of decreased olfaction, decreased olfactory function as measured by the UPSIT is not be taken as satisfying this risk factor criterion.
  3. REM Behavior Disorder (RBD) is identified by a history of sleep-related, injurious, potentially injurious, or disruptive behaviors (i.e., dream enactment behavior). Although polysomnographic evidence of REM sleep without atonia is a supportive clinical laboratory finding, the occurrence of these sleep-related abnormal behaviors is considered necessary and sufficient to satisfy the risk factor criterion. To satisfy the 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 is assessed by measurement of the blood pressure after the subject has been supine at rest for at least 15 minutes and then after the subject has stood upright for 5 minutes. A fall in systolic pressure of 20 mm Hg or more and a fall in diastolic pressure of 10 mm Hg or more at the time of the Screening Examination satisfy this risk factor criterion.

EXCLUSION CRITERIA:

  1. Age< TAB> - 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. Persons with dementia interfering with their ability to provide informed consent are excluded. If dementia is suspected, such as by score on the mini-mental status examination of < 24, then a bioethics consult will be obtained. If a subject develops dementia during the study, with a mini-mental score < 24, the subject is excluded from further participation in the study. Persons who are unable to undergo MRI safely, due to implanted metal, are excluded from the MRI procedure. A candidate participant will be 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. A candidate participant will be excluded if the person is taking a medication that cannot safely be discontinued or replaced temporarily. An example of such a medication is a tricyclic anti-depressant. If it is decided that discontinuing anticoagulant medications would be unsafe, then the subject will be excluded from the lumbar puncture procedure.
  5. Herbal Medicines and Dietary Supplements - If a subject wishes to continue herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subject may participate, 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. If it is medically contraindicated to have an MRI or a lumbar puncture subjects will be excluded from those procedures.
  7. Pregnancy - Pregnant or lactating women are excluded. Women of childbearing potential must have a negative urine or blood test for pregnancy done within 24 hours before any testing involving radioactivity.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775853

Contacts
Contact: Janna Peries, R.N. (301) 435-5166 jperies@ninds.nih.gov
Contact: David S Goldstein, M.D. (301) 496-2103 goldsteind@ninds.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: Sandra Pechnik    301-435-5166    pechniks@ninds.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: David S Goldstein, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00775853     History of Changes
Other Study ID Numbers: 090010, 09-N-0010
Study First Received: October 17, 2008
Last Updated: July 12, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Biomarkers
Catecholamines
18F-Fluoro-L-dopa
Fluorodopamine
Parkinson's Disease
Parkinson Disease
PD

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

ClinicalTrials.gov processed this record on July 20, 2014