| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Parkinson Disease - Autonomic Nervous System Diseases - Pure Autonomic Failure |
| Purpose: |
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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
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| Study summary: |
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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. |
| Criteria: |
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- 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 - 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 is excluded if, in the opinion of the Principal
Investigator, the medical risk outweighs the potential scientific benefit.
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 less than 24, then a bioethics consult will be obtained. If a subject
develops dementia during the study, with a mini-mental score less than 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.
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. If it is
decided that discontinuing medications would be unsafe, then the subject is excluded
from the study.
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 may be excluded. People also may be
excluded if they cannot tolerate having an MRI or having a lumbar puncture.
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. |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
https://pdrisk.ninds.nih.gov
Email: pdrisk@ninds.nih.gov
Phone: (301) 496-1115 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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