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

Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129181
• Other study ID #: AMAD001
• Status: Completed
• Phase: N/A
• First received: August 9, 2005
• Last updated: August 27, 2009
• Start date: January 2005
• Est. completion date: January 2007

Study information

• Verified date: August 2009
• Source: Institute for Neurodegenerative Disorders
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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 After twelve weeks carbidopa/levodopa and cabergoline treatment will be withdrawn and all subjects will undergo SPECT imaging with DATscan after 8 weeks (20 weeks after baseline).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2007
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinsonian Syndrome

Intervention

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).
• 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).

Locations

Country	Name	City	State
Austria	Department of Neurology, Innsbruck Medical University	Innsbruck
Austria	Neurological Department, Wilhelminenspital	Vienna
Germany	Dept. of Neurology, University of Leipzig	Leipzig
Germany	Dept. of Neurology Marburg, Phillips-Univ.	Marburg
Germany	Ambulanz für Bewegungsstörungen, Neurologische Poliklinik	München
Italy	University of Catania-Department of Neurosciences	Catania
Italy	Parkinson Institute Milan	Milan
Italy	Department of Neurological Sciences-University of Napoli	Naples
Spain	Hospital General Universitario Gregorio Marañón	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Institute for Neurodegenerative Disorders	GE Healthcare, Pfizer

Countries where clinical trial is conducted

Austria,  Germany,  Italy,  Spain, 

References & Publications (17)

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the influence of short-term levodopa therapy on dopamine transporter density in early Parkinson's disease		1 year	No
Secondary	To determine the influence of short-term treatment with cabergoline on dopamine transporter density in early Parkinson's disease		1 year	No
Secondary	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		2 years	No