Positron Emission Tomography (PET) Imaging in People With Gaucher Mutations

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: NCT00302146
Recruitment Status : Completed
First Posted : March 13, 2006
Last Update Posted : May 24, 2018
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief 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.

Condition or disease
Glucocerebrosidase Mutations Gaucher Disease

Detailed Description:
An association between Gaucher disease and parkinsonism has been demonstrated by the concurrence of parkinsonian manifestations in patients with Gaucher disease and an increased incidence of glucocerebrosidase (GBA) mutations in subjects with parkinsonism of various ethnicities. Furthermore, there is a significant number of obligate and confirmed Gaucher carriers with parkinsonian manifestations. Thus, alterations in GBA appear to be a more common risk factor than previously thought for the development of sporadic Parkinson disease and related disorders. 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 that will employ multiple imaging modalities to better define the phenotype in GBA-associated parkinsonism, follow disease progression, and identify at-risk individuals. The subjects include patients with Gaucher disease and Gaucher carriers with parkinsonian manifestations, and clinically unaffected but at-risk individuals carrying GBA mutations, and have/ a first degree relative with parkinsonism. The control groups consist of individuals with Gaucher disease but no parkinsonian symptoms, relatives of probands without GBA mutations, PD patients without GBA mutations, and healthy volunteers. Positron emission tomography (PET) with 6-[F-18] Fluoro-L-Dopa (6FD) will be used to evaluate presynaptic dopaminergic function, where 6FD uptake in putamen and striatum will be employed as a measure of neuronal structural integrity in substantia nigra. Each subject will be screened with an MRI to rule-out anatomic brain abnormalities, and to further delineate areas of interest in the PET scans. Subjects will also undergo transcranial ultrasonography (TCS) to assess the substantia nigra non-invasively. 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. In addition to the imaging studies, all patients will undergo a physical and neurological examination, neurocognitive evaluation, and olfactory testing.

Study Type : Observational
Actual Enrollment : 64 participants
Official Title: Functional Imaging in Subjects With Glucocerebrosidase Mutations
Study Start Date : March 10, 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Gaucher Disease

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

The study will include adult subjects age 21 or older carrying GBA mutations. The two major study groups will include subjects with parkinsonism and unaffected subjedcts yet at risk with a first degree family member with parkinsonism.

Controls will include subjects without GBA mutations, with sporadic PD and healthy volunteers who do not have a family history of parkinsonism or Gaucher disease.

Healthy Volunteers and Control subjects will be matched for age, gender and handedness for statistical purposes.


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.

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): NCT00302146

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Principal Investigator: Grisel J Lopez, M.D. National Human Genome Research Institute (NHGRI)

Additional Information:
Publications: Identifier: NCT00302146     History of Changes
Other Study ID Numbers: 060055
First Posted: March 13, 2006    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: November 24, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Lysosomal Storage Disorder
L-Dopa Uptake
Gaucher Disease
Parkinson Disease
Healthy Volunteer

Additional relevant MeSH terms:
Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders