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

NCT00302146 | Completed FDA Drug

• 2 other identifiers: 06005506-HG-0055
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Gaucher Disease; Parkinson Disease

Keywords

Lysosomal Storage Disorder; Carrier; L-Dopa Uptake; Glucocerebrosidase; Pathogenesis; Natural History; Gaucher Disease; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Imaging techniques

  Imaging techniques will evaluate whether there are early changes in cerebral L-Dopa stores associated with glucocerebrosidase mutations in subjects with and without parkinsonism.

  Ongoing

Study Arms (3)

Asymptomatic

Unaffected at-risk individuals with or without a first degree family member with parkinsonism, GD with and without a family history of PD, Gaucher carriers with and without a family history of PD.

Drug: 15-0 H20

Control

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.

Drug: 15-0 H20

PD

Subjects with parkinsonism to better characterize the parkinsonian phenotype (e.g.,GD/PD, Sporadic PD, Gaucher carrier PD).

Drug: 15-0 H20

Interventions

15-0 H20 DRUG

Asymptomatic; Control; PD

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will include adult subjects age 21 or older. There will be two major study groups. The first will include subjects with parkinsonism to better characterize the parkinsonian phenotype and the second group will have unaffected yet at-risk individuals with or without a first degree family member with parkinsonism to explore early signs and symptoms of disease. Control subjects will include individuals without GBA1 mutations. Subjects with sporadic PD and healthy volunteers who do not have a family history of parkinsonism or Gaucher disease will be enrolled as control subjects.

You may qualify if:

• The study will include adult subjects age 21 or older. There will be two major study groups. The first will include subjects with parkinsonism to better characterize the parkinsonian phenotype and the second group will have unaffected yet at-risk individuals with or without a first degree family member with parkinsonism to explore early signs and symptoms of disease.
• Control subjects will include individuals without GBA1 mutations. Subjects with sporadic PD and healthy volunteers who do not have a family history of parkinsonism or Gaucher disease will be enrolled as control subjects.
• Healthy volunteers and control subjects with parkinsonism will be matched for age, gender and handedness for statistical purposes. When available, we would like to study unaffected siblings (without GBA1 mutations) of parkinsonian subjects. Sib-pair studies will especially be valuable to exclude both environmental and other genetic risk factors for the development of parkinsonian manifestations.

You may not qualify if:

• Subjects excluded from the study include those:
• with severe cognitive deficits impairing decision making at time of enrollment without an appointed surrogate decision maker.
• who are unable or it is medically unsafe to withdraw from their current medications, such as subjects on psychoactive medications. The subjects on medications that may affect CNS function may be included in the study only with an approval from the prescribing physician to discontinue their medications temporarily for the study.
• pregnant or nursing. All women of child bearing potential will undergo a pregnancy test.
• with a history of neurologic conditions such as stroke or any focal brain lesion that may result in parkinsonian manifestations, including subjects with deep brain stimulators
• cannot lie on his/her back for a prolonged period of time

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1093/qjmed/89.9.691.

  PMID: 8917744 BACKGROUND

• 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. doi: 10.1016/s1096-7192(03)00071-4.

  PMID: 12809640 BACKGROUND

• 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. doi: 10.1016/j.ymgme.2004.04.011.

  PMID: 15234332 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Parkinson Disease; Gaucher Disease; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Ellen Sidransky, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2006
• First Posted: March 13, 2006
• Study Start: May 23, 2006
• Last Updated: May 7, 2026

Record last verified: 2026-03-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: pending
• Access Criteria: pending

Locations

US (1)