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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Molecular NeuroImaging
- Enrollment
- 3
- Primary Endpoint
- The primary outcome will be the reduction from baseline in IBZM striatal uptake during a 6-8 hour assessment period after treatment.
Study Overview
Brief Summary
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.
Detailed Description
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 30 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
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
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Secondary Measures include: Putamen and caudate uptake over time, UPDRS scores, and Pharmacokinetic analysis.(6-8hrs)