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

Parkinson's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00200447
• Other study ID #: MNI 0011
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: January 17, 2008
• Start date: March 2004
• Est. completion date: September 2004

Study information

• Verified date: January 2008
• Source: Molecular NeuroImaging
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: September 2004
• Est. primary completion date: September 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• carbidopa/l-dopa

• carbidopa/l-dopa/entacapone

• Stalevo

Procedure:
• [123I]-IBZM imaging

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Molecular NeuroImaging

References & Publications (5)

Castner SA, al-Tikriti MS, Baldwin RM, Seibyl JP, Innis RB, Goldman-Rakic PS. Behavioral changes and [123I]IBZM equilibrium SPECT measurement of amphetamine-induced dopamine release in rhesus monkeys exposed to subchronic amphetamine. Neuropsychopharmacology. 2000 Jan;22(1):4-13. — View Citation

de la Fuente-Fernández R, Lu JQ, Sossi V, Jivan S, Schulzer M, Holden JE, Lee CS, Ruth TJ, Calne DB, Stoessl AJ. Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover. Ann Neurol. 2001 Mar;49(3):298-303. — View Citation

Laruelle M, D'Souza CD, Baldwin RM, Abi-Dargham A, Kanes SJ, Fingado CL, Seibyl JP, Zoghbi SS, Bowers MB, Jatlow P, Charney DS, Innis RB. Imaging D2 receptor occupancy by endogenous dopamine in humans. Neuropsychopharmacology. 1997 Sep;17(3):162-74. — View Citation

Seibyl JP, Woods SW, Zoghbi SS, Baldwin RM, Dey HM, Goddard AW, Zea-Ponce Y, Zubal G, Germine M, Smith EO, et al. Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. J Nucl Med. 1992 Nov;33(11):1964-71. — View Citation

Seibyl JP, Zea-Ponce Y, Brenner L, Baldwin RM, Krystal JH, Offord SJ, Mochoviak S, Charney DS, Hoffer PB, Innis RB. Continuous intravenous infusion of iodine-123-IBZM for SPECT determination of human brain dopamine receptor occupancy by antipsychotic agent RWJ-37796. J Nucl Med. 1996 Jan;37(1):11-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome will be the reduction from baseline in IBZM striatal uptake during a 6-8 hour assessment period after treatment.		6-8hrs	No
Secondary	Secondary Measures include: Putamen and caudate uptake over time, UPDRS scores, and Pharmacokinetic analysis.		6-8hrs	No