Study of the Effects of Dopaminergic Medications on Dopamine Transporter Density in Subjects With Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT00129181
• Recruitment Status: Completed
• First Posted: August 11, 2005
• Last Update Posted: August 28, 2009
• Sponsor: Institute for Neurodegenerative Disorders
• Collaborators: Pfizer; GE Healthcare
• Information provided by: Institute for Neurodegenerative Disorders

Study Description

Brief Summary:

This study investigates whether there is a change in 123iodine-2ß- carbomethoxy-3ß-(4-iodophenyl) tropane ([123I]ß-CIT) uptake after short-term treatment with levodopa compared to either dopamine agonist or placebo.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease; Parkinsonian Syndrome	Drug: cabergoline; Drug: carbidopa/levodopa; Procedure: DATscan and SPECT imaging	Not Applicable

Detailed Description:

This is a multi-center, open-label study of short-term treatment with levodopa or cabergoline on striatal DATscan uptake in early Parkinson's disease. Approximately 120 Parkinson's disease subjects will be randomized to receive either carbidopa/levodopa, cabergoline or no treatment during a twelve week period. Subjects will undergo SPECT imaging with DATscan at screening and after 12 weeks. After twelve weeks carbidopa/levodopa and cabergoline treatment will be withdrawn and all subjects will undergo SPECT imaging with DATscan after 8 weeks (20 weeks after baseline).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Diagnostic
• Official Title: A Single-blinded Assessment of the Short-term Effects of Cabergoline vs. Carbidopa/Levodopa on SPECT Dopamine Transporter Density in Out-patient Subjects With Parkinson's Disease
• Study Start Date: January 2005
• Actual Primary Completion Date: December 2006
• Actual Study Completion Date: January 2007

Arms and Interventions

Intervention Details:

• Drug: cabergoline
  Approximately 120 Parkinson's disease subjects will be randomized to receive either carbidopa/levodopa, cabergoline or no treatment during a twelve week period. Subjects will undergo SPECT imaging with DATscan at screening and after 12 weeks. After twelve weeks carbidopa/levodopa and cabergoline treatment will be withdrawn and all subjects will undergo SPECT imaging with DATscan after 8 weeks (20 weeks after baseline).
• Drug: carbidopa/levodopa
  Approximately 120 Parkinson's disease subjects will be randomized to receive either carbidopa/levodopa, cabergoline or no treatment during a twelve week period. Subjects will undergo SPECT imaging with DATscan at screening and after 12 weeks. After twelve weeks carbidopa/levodopa and cabergoline treatment will be withdrawn and all subjects will undergo SPECT imaging with DATscan after 8 weeks (20 weeks after baseline).
• Procedure: DATscan and SPECT imaging
  Approximately 120 Parkinson's disease subjects will be randomized to receive either carbidopa/levodopa, cabergoline or no treatment during a twelve week period. Subjects will undergo SPECT imaging with DATscan at screening and after 12 weeks. After twelve weeks carbidopa/levodopa and cabergoline treatment will be withdrawn and all subjects will undergo SPECT imaging with DATscan after 8 weeks (20 weeks after baseline).

Outcome Measures

Primary Outcome Measures :

1. To determine the influence of short-term levodopa therapy on dopamine transporter density in early Parkinson's disease [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. To determine the influence of short-term treatment with cabergoline on dopamine transporter density in early Parkinson's disease [ Time Frame: 1 year ]
2. To further develop the AMADEUS consortium, a collaboration of clinical-imaging SPECT DAT sites able to obtain data using comparable techniques and transmit imaging to a central analysis site [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The subject is aged 40 years or older.
• Written informed consent is obtained.
• Subjects have a clinical diagnosis of idiopathic Parkinson's disease.
• Hoehn and Yahr stages for subjects are I-II.

Exclusion Criteria:

• The subject has atypical or drug-induced Parkinson's disease.
• The subject has dementia.
• The subject has clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness.
• The subject is pregnant.

Contacts and Locations

Locations

Austria

Department of Neurology, Innsbruck Medical University

Innsbruck, Austria, 6020

Neurological Department, Wilhelminenspital

Vienna, Austria, 1160

Germany

Dept. of Neurology, University of Leipzig

Leipzig, Germany, 04103

Dept. of Neurology Marburg, Phillips-Univ.

Marburg, Germany, 35039

Ambulanz für Bewegungsstörungen, Neurologische Poliklinik

München, Germany, 81377

Italy

University of Catania-Department of Neurosciences

Catania, Italy, 95123

Parkinson Institute Milan

Milan, Italy

Department of Neurological Sciences-University of Napoli

Naples, Italy, 80131

Spain

Hospital General Universitario Gregorio Marañón

Madrid, Spain, 28007

Sponsors and Collaborators

Institute for Neurodegenerative Disorders

Pfizer

GE Healthcare

Investigators

• Principal Investigator: Kenneth L Marek, MD; The Institute for Neurodegenerative Disorders
• Principal Investigator: John P Seibyl, MD; The Institute for Neurodegenerative Disorders

More Information

Publications:

Ahlskog JE. Slowing Parkinson's disease progression: recent dopamine agonist trials. Neurology. 2003 Feb 11;60(3):381-9. Review.

Ahlskog JE, Uitti RJ, O'Connor MK, Maraganore DM, Matsumoto JY, Stark KF, Turk MF, Burnett OL. The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson's disease. Mov Disord. 1999 Nov;14(6):940-6.

Brücke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wöber C, Müller C, Podreka I. Measurement of the dopaminergic degeneration in Parkinson's disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Transm Suppl. 1997;50:9-24.

Fahn S. Is levodopa toxic? Neurology. 1996 Dec;47(6 Suppl 3):S184-95. Review.

Guttman M, Stewart D, Hussey D, Wilson A, Houle S, Kish S. Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology. 2001 Jun 12;56(11):1559-64.

Innis RB, Seibyl JP, Scanley BE, Laruelle M, Abi-Dargham A, Wallace E, Baldwin RM, Zea-Ponce Y, Zoghbi S, Wang S, et al. Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11965-9.

Innis RB, Marek KL, Sheff K, Zoghbi S, Castronuovo J, Feigin A, Seibyl JP. Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]beta-CIT. Mov Disord. 1999 May;14(3):436-42.

Little KY, Gorebig J, Carroll FI, Mapili J, Meador-Woodruff JH. Lack of dopamine receptor agonists effect on striatal dopamine transporter binding sites. Brain Res. 1996 Dec 2;742(1-2):313-6.

Marek K, Innis R, van Dyck C, Fussell B, Early M, Eberly S, Oakes D, Seibyl J. [123I]beta-CIT SPECT imaging assessment of the rate of Parkinson's disease progression. Neurology. 2001 Dec 11;57(11):2089-94.

Morrish PK, Rakshi JS, Bailey DL, Sawle GV, Brooks DJ. Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F]dopa PET. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):314-9.

Nurmi E, Bergman J, Eskola O, Solin O, Hinkka SM, Sonninen P, Rinne JO. Reproducibility and effect of levodopa on dopamine transporter function measurements: a [18F]CFT PET study. J Cereb Blood Flow Metab. 2000 Nov;20(11):1604-9.

Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002 Apr 3;287(13):1653-61.

Fahn S; Parkinson Study Group. Does levodopa slow or hasten the rate of progression of Parkinson's disease? J Neurol. 2005 Oct;252 Suppl 4:IV37-IV42. Review.

Rioux L, Frohna PA, Joyce JN, Schneider JS. The effects of chronic levodopa treatment on pre- and postsynaptic markers of dopaminergic function in striatum of parkinsonian monkeys. Mov Disord. 1997 Mar;12(2):148-58.

Schapira AH. Dopamine agonists and neuroprotection in Parkinson's disease. Eur J Neurol. 2002 Nov;9 Suppl 3:7-14. Review.

Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ; REAL-PET Study Group. Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol. 2003 Jul;54(1):93-101.

Wooten GF. Agonists vs levodopa in PD: the thrilla of whitha. Neurology. 2003 Feb 11;60(3):360-2.

• ClinicalTrials.gov Identifier: NCT00129181
• Other Study ID Numbers: AMAD001
• First Posted: August 11, 2005
• Last Update Posted: August 28, 2009
• Last Verified: August 2009

Keywords provided by Institute for Neurodegenerative Disorders:

parkinson; brain imaging; 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; Levodopa; Carbidopa; Cabergoline; Carbidopa, levodopa drug combination; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Aromatic Amino Acid Decarboxylase Inhibitors; Enzyme Inhibitors; Dopamine Agonists; Adjuvants, Immunologic; Immunologic Factors