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

Condition(s) targeted: Parkinson Disease; Parkinsonian Syndrome

Intervention: cabergoline (Drug); carbidopa/levodopa (Drug); DATscan and SPECT imaging (Procedure)

Phase: N/A

Status: Completed

Sponsored by: Institute for Neurodegenerative Disorders

Official(s) and/or principal investigator(s):
Kenneth L Marek, MD, Principal Investigator, Affiliation: The Institute for Neurodegenerative Disorders
John P Seibyl, MD, Principal Investigator, Affiliation: The Institute for Neurodegenerative Disorders

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.

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 design: Diagnostic, Randomized, Single Blind (Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To determine the influence of short-term levodopa therapy on dopamine transporter density in early Parkinson's disease

Secondary outcome:

To determine the influence of short-term treatment with cabergoline on dopamine transporter density in early Parkinson's disease

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

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 After twelve weeks carbidopa/levodopa and cabergoline treatment will be withdrawn and all subjects will undergo SPECT imaging with DATscan after 8 weeks (20 weeks after baseline).

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

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.

Department of Neurology, Innsbruck Medical University, Innsbruck 6020, Austria

Neurological Department, Wilhelminenspital, Vienna 1160, Austria

Ambulanz für Bewegungsstörungen, Neurologische Poliklinik, München 81377, Germany

Dept. of Neurology, University of Leipzig, Leipzig 04103, Germany

Dept. of Neurology Marburg, Phillips-Univ., Marburg 35039, Germany

Parkinson Institute Milan, Milan, Italy

University of Catania-Department of Neurosciences, Catania 95123, Italy

Department of Neurological Sciences-University of Napoli, Naples 80131, Italy

Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain

Related 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.

Brucke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wober C, Muller 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. No abstract available.

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.

Parkinson Study Group. Does levodopa slow or hasten the rate of progression of Parkinson's disease? The results of the ELLDOPA trial. Neurology 2003; 60(5) Suppl1: A80-A81.

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. No abstract available.

Starting date: January 2005
Ending date: January 2007
Last updated: November 1, 2007