Positron Emission Tomography (PET) Imaging in People With Gaucher Mutations
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Glucocerebrosidase Mutations; Gaucher Disease
Phase: N/A
Status: Recruiting
Sponsored by: National Human Genome Research Institute (NHGRI) Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
Summary
This study will use positron emission tomography (PET) to compare how people with Gaucher
disease or Gaucher disease carriers with parkinsonism, and their family members, use
dopamine in their brains in comparison with healthy normal volunteers and people who have
Parkinson disease. PET assesses organ function by measuring metabolism. In this study,
magnetic resonance imaging (MRI) is used in conjunction with PET to help better interpret
and understand the information gleaned from PET.
People 21 years of age and older with the following conditions may be eligible for this
study:
- Gaucher disease and parkinsonism
- Parkinsonism and a family history of Gaucher disease
- Gaucher disease and a family history of parkinsonism
- Gaucher disease carriers who have parkinsonism or a family history of parkinsonism
- Unaffected people with a family history of Gaucher disease and parkinsonism
- Healthy volunteers
Participants undergo the following tests and procedures:
- Personal and family medical history
- Physical examination
- PET scan: The subject lies on a table that slides into the PET scanner until his or her
head is positioned properly in the scanner. A catheter is inserted into a vein. An
initial scan is done to obtain images before radionuclides are injected. Radioactive
water is then injected through the catheter and the subject is asked questions in order
to stimulate blood flow in certain areas of the brain to show what parts of the brain
are activated. Fluorodopa is then infused through the catheter over 3 minutes. The PET
scan can last up to 2 hours.
- MRI scan: This test uses a magnetic field and radio waves to obtain images of organs.
The subject lies still on a bed in the middle of a circular scanner for about 30
minutes.
Clinical Details
Official title: Functional Imaging in Subjects With Glucocerebrosidase Mutations
Study design: N/A
Detailed description:
An association between Gaucher disease and parkinsonism has been demonstrated by the
concurrence of parkinsonian manifestations in over 30 patients with Gaucher disease and an
increased incidence of glucocerebrosidase mutations in subjects with parkinsonism.
Furthermore, there appears to be a significant number of obligate and confirmed Gaucher
carriers with parkinsonian manifestations. Thus, glucocerebrosidase mutations may be a risk
factor for development of parkinsonism. However in affected and at-risk individuals, the
identification and characterization of early parkinsonian manifestations and the rate of
progression of symptoms have not been studied objectively. We propose an in-vivo study of
regional cerebral dopamine neurochemistry and blood flow in subjects with glucocerebrosidase
mutations. Presynaptic dopaminergic function and cerebral blood flow will be assessed using
positron emission tomography (PET) with 6-[F-18] Fluoro-L-DOPA (6FD) and 15 O-H2O in a
single PET session. The subjects will include patients with Gaucher disease and Gaucher
carriers with parkinsonism, and/or with a family history of a first degree relative with
parkinsonism. The control group will include family members lacking glucocerebrosidase
mutations, age matched healthy controls, and subjects with parkinsonism without
glucocerebrosidase mutations. The kinetic rate constant (Ki) for striatal dopaminergic
uptake will be calculated. Using bivariate analysis we will compare the Ki in groups of
subjects with glucocerebrosidase mutations, with and without parkinsonian manifestations,
with aged-matched healthy volunteers, to identify potential abnormalities in striatal and
putamenal presynaptic F-dopa uptake. Each subject will be screened with an MRI to rule-out
structural abnormalities, and to further delineate areas of interest in the PET scans.
Subjects will also undergo transcranial ultrasonography (TCS) to assess echogenicity of the
midbrain. This study will help us to identify abnormalities in L-Dopa uptake in subjects
with glucocerebrosidase mutations, to better define the associated parkinsonian phenotype,
follow the progression of parkinsonian manifestations and identify "at-risk" indiviuals.
The baseline data regarding L-Dopa metabolism in subjects with glucocerebrosidase mutations
will enable us to estimate the frequency and earliest onset of parkinsonian symptoms in
at-risk subjects. The results of both the PET scans and TCS will be kept confidential, and
will not be communicated to the individuals or families involved in the study.
Eligibility
Minimum age: 21 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
The study will include adult subjects age 21 or older with Gaucher disease with and
without parkinsonism and individuals from families with a Gaucher proband and a history of
parkinsonism.
Controls will include unaffected siblings of patients with Gaucher disease and subjects
with sporadic PD, without glucocerebrosidase mutations, and healthy volunteers who do not
have a family history of parkinsonism or Gaucher disease.
Volunteers will be matched for age, gender and handedness for statistical purposes.
EXCLUSION CRITERIA:
The subjects excluded from the study are those:
1. with severe cognitive deficits impairing decision making
2. unable or medically unsafe to withdraw from their current medications, such as
subjects on SSRIs and other psychoactive drugs.
3. pregnant or nursing. All women of child bearing potential will undergo a pregnancy
test.
4. With a history of neurologic conditions such as stroke or any focal brain lesion that
may result in parkinsonian manifestations. Individuals with such MRI findings will
be excluded from the study.
Locations and Contacts
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting
Additional Information
NIH Clinical Center Detailed Web Page
Related publications: Neudorfer O, Giladi N, Elstein D, Abrahamov A, Turezkite T, Aghai E, Reches A, Bembi B, Zimran A. Occurrence of Parkinson's syndrome in type I Gaucher disease. QJM. 1996 Sep;89(9):691-4. Tayebi N, Walker J, Stubblefield B, Orvisky E, LaMarca ME, Wong K, Rosenbaum H, Schiffmann R, Bembi B, Sidransky E. Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol Genet Metab. 2003 Jun;79(2):104-9. Wong K, Sidransky E, Verma A, Mixon T, Sandberg GD, Wakefield LK, Morrison A, Lwin A, Colegial C, Allman JM, Schiffmann R. Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab. 2004 Jul;82(3):192-207.
Starting date: March 2006
Last updated: October 2, 2009
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