![]() |
Home
Search
Study Topics
Glossary
|
![]() |
![]() |
|
![]() |
|
![]() |
|
![]() |
![]() |
![]() |
|
![]() |
![]() |
Sponsored by: |
National Human Genome Research Institute (NHGRI) |
---|---|
Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00302146 |
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:
Participants undergo the following tests and procedures:
Condition |
---|
Glucocerebrosidase Mutations Gaucher Disease |
Study Type: | Observational |
Official Title: | Functional Imaging in Subjects With Glucocerebrosidase Mutations |
Estimated Enrollment: | 100 |
Study Start Date: | March 2006 |
Estimated Primary Completion Date: | October 2010 (Final data collection date for primary outcome measure) |
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.
Ages Eligible for Study: | 21 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
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:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Study ID Numbers: | 060055, 06-HG-0055 |
Study First Received: | March 11, 2006 |
Last Updated: | August 24, 2009 |
ClinicalTrials.gov Identifier: | NCT00302146 History of Changes |
Health Authority: | United States: Federal Government |
Lysosomal Storage Disorder Carrier L-Dopa Uptake Glucocerebrosidase Pathogenesis Carbidopa Gaucher Disease Parkinson Disease |
[O-15]-Water 6-[F-18]Fluoro-L-dopa Lysosomal Storage Disorder Gaucher Disease Carrier Healthy Volunteer HV |
Lipid Metabolism, Inborn Errors Levodopa Sphingolipidoses Metabolic Diseases Lysosomal Storage Diseases Carbidopa Sphingolipidosis Central Nervous System Diseases Healthy Brain Diseases Lymphatic Diseases |
Metabolism, Inborn Errors Genetic Diseases, Inborn Parkinson Disease Dihydroxyphenylalanine Brain Diseases, Metabolic, Inborn Lipidoses Gaucher Disease Metabolic Disorder Lipid Metabolism Disorders Brain Diseases, Metabolic |
Lipid Metabolism, Inborn Errors Sphingolipidoses Metabolic Diseases Reticuloendotheliosis Lysosomal Storage Diseases, Nervous System Lysosomal Storage Diseases Nervous System Diseases Central Nervous System Diseases Brain Diseases |
Lymphatic Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Brain Diseases, Metabolic, Inborn Lipidoses Gaucher Disease Lipid Metabolism Disorders Brain Diseases, Metabolic |