Imaging and Genetic Biomarkers of Parkinson Disease (PD) Onset and Progression in High-risk Families

This study has been completed.
Sponsor:
Collaborators:
Molecular NeuroImaging
Information provided by (Responsible Party):
Kenneth Marek, MD, Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier:
NCT00273351
First received: January 4, 2006
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by rigidity, bradykinesia, postural instability, and tremor. Clinical decline reflects ongoing degeneration of dopamine-containing neurons. A critical unmet need for clinical research is to improve early detection of these diseases by developing tools to assist with earlier diagnosis. Biomarkers are broadly defined as characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention (Biomarkers Defintions Working Group 2001). Development of reliable biomarkers for PD would dramatically accelerate research on PD etiology, pathophysiology, disease progression and therapeutics. Specific biomarkers may be useful at the onset of neurodegeneration, the onset of disease, and/or to mark disease progression. The biomarkers in this study include brain imaging with a radioactively labelled drug (Beta-CIT), computerized testing of memory, attention, motor speed, judgment and handwriting, and assessments of speech and smell. Subjects may also be asked to provide a blood sample for genetic and biochemical testing.


Condition Intervention Phase
Parkinson Disease
Parkinsonian Syndrome
Drug: [123I]B-CIT
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Assessment of Pre-symptomatic and Symptomatic Patients With Parkinson Disease to Identify and Characterize Genetic and Phenotypic Biomarkers for Disease Onset and Progression.

Resource links provided by NLM:


Further study details as provided by Institute for Neurodegenerative Disorders:

Primary Outcome Measures:
  • Dopamine transporter density [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
    The dopamine transporter density in individuals at risk for Parkinsonism due to family history compared to healthy controls.


Secondary Outcome Measures:
  • Correlation of the imaging outcome with both clinical outcomes (olfaction, reaction time, handwriting, etc) and biochemical measures [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]

Enrollment: 62
Study Start Date: January 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: [123I]B-CIT
[123I]B-CIT and SPECT imaging
Drug: [123I]B-CIT
Subjects will receive up to 6 mCi of [123I] B-CIT injected intravenously
Other Name: [123I]B-CIT

Detailed Description:

Individuals who agree to participate in this trial will have a complete screening exam by a neurologist at the Institute for Neurodegenerative Disorders (IND) in New Haven, CT. The exam may include blood tests, urine tests and an electrocardiogram (ECG -tracing of the electrical activity of the heart) to determine eligibility for the trial.

Research subjects will participate in a variety of biomarker assessments including brain imaging, which will take place over a period of two days.

On the first day subjects report to IND after a brief exam subjects will receive a standard dose of Lugol's solution (potassium iodide) by mouth to decrease uptake of the radioactive drug into the thyroid gland. Subjects will be given a standard dose of potassium perchlorate if allergic to iodine.

Next subjects will receive the intravenous (IV - into a vein) injection of the Beta-CIT, a radioactive material that localizes in the brain.

On the second day, about 24 hours after the injection, subjects will return to IND for a SPECT scan. The SPECT camera takes a "picture" of the radiation emitted by the Beta-CIT. This procedure will take approximately 30 minutes.

Subjects will be contacted by phone one week following the injection to monitor adverse (bad or harmful) events possibly related to the imaging procedure.

This two-day imaging procedure, comprehensive neurological testing, and blood collection for genetics and biochemical testing may be repeated every 12 to 18 months during the next five years.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >21
  • Previous participation in the Progeni or Core PD clinical study
  • A diagnosis of parkinsonism or a family history of parkinsonism
  • Normal screening laboratory studies including:
  • complete blood count
  • chemistries
  • urinalysis

Exclusion Criteria:

  • Pregnancy
  • Psychiatric disease other than history of depression
  • Significant medical disease including abnormalities on screening biochemical or hematological labs or abnormal ECG.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00273351

Locations
United States, Connecticut
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Institute for Neurodegenerative Disorders
Molecular NeuroImaging
Investigators
Principal Investigator: Kenneth L. Marek, MD President and Senior Scientist
  More Information

Publications:
Marek, K., J. Seibyl, et al. (1999). "[123I] ß-CIT/SPECT: Assessment of determinants of variability in progression of Parkinson's disease." Neurology 52: A91-92.
Marek, K., J. Seibyl, et al. (1996). "Dopamine transporter and receptor imaging in Parkinsonism. (Presented at the 4th International Congress of Movement Disorders, Vienna, Austria; June, 1996.)." Mov Dis 6.
Seibyl, J. P., K. L. Marek, et al. (1994). "[123I] B-CIT SPECT imaging in idiopathic parkinson's disease: correlation of striatal binding abnormality with disease severity [abstract]." Mov Disord 9(Suppl 1): 89.
Tanner, C. (1994). Epidemiologic clues to the cause of Parkinson's disease. Movement Disorders 3. S. Fahn and C. Marsden. Oxford, Butterworth-Heinemann: 124-146.
van Dyck, C., J. Seibyl, et al. (1995). "Age-related Decline in Dopamine Transporter Binding in Human Striatum with [123I]ß-CIT SPECT." J Nucl Med 36: 1175-1181.

Responsible Party: Kenneth Marek, MD, Principal Investigator, Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier: NCT00273351     History of Changes
Other Study ID Numbers: PROSPECT
Study First Received: January 4, 2006
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Institute for Neurodegenerative Disorders:
Parkinson
family history
diagnosis

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on July 20, 2014