An Open-Label Feasibility/Pilot Study With [123I]-IBZM SPECT (DOPA-SYN)

Official Title: “Assessment of Carbidopa/l-Dopa and Carbidopa/l Dopa/Entacapone on Synaptic Dopamine in Parkinson's Patients: An Open-Label Feasibility/Pilot Study With [123I]-IBZM SPECT (DOPA-SYN)”

This study conducted to more fully evaluate the way that carbidopa/levodopa and entacapone may work in the brain. This research study uses [123I]-IBZM and dynamic SPECT imaging to determine the amount and the duration of dopamine release from specific regions in the brain after treatment with either the combination of carbidopa/levodopa or the combination of carbidopa/levodopa/entacapone.

This is a pilot evaluation of dopaminergic function in PD using a bolus plus constant infusion protocol with [123I]-IBZM and SPECT to evaluate the potential for carbidopa/l-dopa alone or carbidopa/l-dopa/entacapone to produce displacement of striatal radioactivity for assessment of intrasynaptic dopamine. We will assess the feasibility of this paradigm for detecting l-dopa effects on the SPECT signal in subjects with PD with disease duration of greater than 4yrs and with a stable response to L-dopa. Each subject will undergo three [123I]-IBZM studies separated by 1-2 weeks. Subjects will be off medication for at least 12 h prior to study For each of the three scan days patients will receive a constant intravenous infusion of [123I]-IBZM over 4-5 hours to establish an equilibrium binding condition of the radiotracer at striatal D2/D3 receptors. Three baseline SPECT acquisitions will be obtained prior to medication dosing to establish a stable baseline. At approximately 5 h after the initiation of the infusion subjects will receive a single oral dose of either carbidopa/levodopa (37.5mg/150mg or 50mg/250mg), or carbidopa/levodopa/entacapone (either 37.5mg/150mg/200mg- STALEVO or 50/250mg/200mg).

Intervention(s) in this Clinical Trial

• Drug: carbidopa/l-dopa
• Drug: carbidopa/l-dopa/entacapone
• Drug: Stalevo
• Procedure: [123I]-IBZM imaging

Primary Measures

• The primary outcome will be the reduction from baseline in IBZM striatal uptake during a 6-8 hour assessment period after treatment.
  • Time Frame: 6-8hrs
    Safety Issue?: No

Secondary Measures

• Secondary Measures include: Putamen and caudate uptake over time, UPDRS scores, and Pharmacokinetic analysis.
  • Time Frame: 6-8hrs
    Safety Issue?: No

Main inclusion criteria:

• The patient is aged 30 years or older.
• Written informed consent is obtained.
• Patients have a diagnosis of idiopathic Parkinson's disease.
• Hoehn and Yahr stages for patients are I-III.
• Patients have a diagnosis> 4 yrs prior to screening
• Patients are treated with carbidopa/levodopa with > 300 mg levodopa.

Main exclusion criteria:

• The patient has atypical or drug-induced Parkinson's disease.
• The patient has dementia (MMSE 24).
• The patient has a clinically significant clinical laboratory values, and/or medical or psychiatric illness.
• The patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
• The patient has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• The patient has been treated with a dopamine agonist within the past 30 days.
• Concomitant treatment with Monoamine Oxidase (MAO)-inhibitors (except selegiline <10 mg/day) within 30 days prior to the screening visit
• Patient has a history of iodine allergy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Molecular NeuroImaging Other

Overall Clinical Trial Officials and Contacts

John P Seibyl, MD Principal Investigator Molecular NeuroImaging  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00200447

Study ID Number: MNI 0011

ClinicalTrials.gov Identifier: NCT00200447

Health Authority: United States: Food and Drug Administration