This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in JAMA  Topic Collections  • Neurology  • Alert me on articles by topic

Parkinson Study Group

JAMA. 2002;287:1653-1661.

Context  Pramipexole and levodopa are effective medications to treat motor symptoms of early Parkinson disease (PD). In vitro and animal studies suggest that pramipexole may protect and that levodopa may either protect or damage dopamine neurons. Neuroimaging offers the potential of an objective biomarker of dopamine neuron degeneration in PD patients.

Objective  To compare rates of dopamine neuron degeneration after initial treatment with pramipexole or levodopa in early PD by means of dopamine transporter imaging using single-photon emission computed tomography (SPECT) with 2-carboxymethoxy-3(4-iodophenyl)tropane (-CIT) labeled with iodine 123.

Design  Substudy of a parallel-group, double-blind randomized clinical trial.

Setting and Patients  Eighty-two patients with early PD who were recruited at 17 clinical sites in the United States and Canada and required dopaminergic therapy to treat emerging disability, enrolled between November 1996 and August 1997.

Interventions  Patients were randomly assigned to receive pramipexole, 0.5 mg 3 times per day with levodopa placebo (n = 42), or carbidopa/levodopa, 25/100 mg 3 times per day with pramipexole placebo (n = 40). For patients with residual disability, the dosage was escalated during the first 10 weeks, and subsequently, open-label levodopa could be added. After 24 months of follow-up, the dosage of study drug could be further modified.

Main Outcome Measures  The primary outcome variable was the percentage change from baseline in striatal [¹²³I]-CIT uptake after 46 months. The percentage changes and absolute changes in striatal, putamen, and caudate [¹²³I]-CIT uptake after 22 and 34 months were also assessed. Clinical severity of PD was assessed using the Unified Parkinson Disease Rating Scale (UPDRS) 12 hours off anti-PD medications.

Results  Sequential SPECT imaging showed a decline in mean (SD) [¹²³I]-CIT striatal uptake from baseline of 10.3% (9.8%) at 22 months, 15.3% (12.8%) at 34 months, and 20.7% (14.4%) at 46 months—approximately 5.2% per year. The mean (SD) percentage loss in striatal [¹²³I]-CIT uptake from baseline was significantly reduced in the pramipexole group compared with the levodopa group: 7.1% (9.0%) vs 13.5% (9.6%) at 22 months (P = .004); 10.9% (11.8%) vs 19.6% (12.4%) at 34 months (P = .009); and 16.0% (13.3%) vs 25.5% (14.1%) at 46 months (P = .01). The percentage loss from baseline in striatal [¹²³I]-CIT uptake was correlated with the change from baseline in UPDRS at the 46-month evaluation (r = - 0.40; P = .001).

Conclusions  Patients initially treated with pramipexole demonstrated a reduction in loss of striatal [¹²³I]-CIT uptake, a marker of dopamine neuron degeneration, compared with those initially treated with levodopa, during a 46-month period. These imaging data highlight the need to further compare imaging and clinical end points of PD progression in long-term studies.

Parkinson Study Group Investigators: Steering Committee: Kenneth Marek, MD, John Seibyl, MD, principal investigators for CALM-PD-CIT, The Institute for Neurodegenerative Disorders, New Haven, Conn; Ira Shoulson, MD, principal investigator for CALM-PD, Robert Holloway, MD, MPH, medical director, Karl Kieburtz, MD, MPH, Michael McDermott, PhD, chief biostatistician, Cornelia Kamp, MBA, CRCC project coordinator, Aileen Shinaman, JD, PSG executive director, University of Rochester, Rochester, NY; Stanley Fahn, MD, coprincipal investigator for CALM-PD, Columbia University, New York, NY; Anthony Lang, MD, Toronto Western Hospital, University Health Network, Toronto, Ontario; William Weiner, MD, University of Maryland, Baltimore; Mickie Welsh, RN, DNS, ex-officio, University of Southern California, Los Angeles.

RELATED LETTER

Brain Imaging to Assess the Effects of Dopamine Agonists on Progression of Parkinson Disease
J. Eric Ahlskog, Demetrius M. Maraganore, Ryan J. Uitti, George R. Uhl, Roger L. Albin, Thomas E. Nichols, Kirk A. Frey, Paul K. Morrish, Kenneth Marek, John Seibyl, Michael McDermott, Stanley Fahn, and Anthony Lang
JAMA. 2002;288(3):311-313.
EXTRACT | FULL TEXT  

RELATED ARTICLE

April 3, 2002
JAMA. 2002;287(13):1735-1736.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Levodopa for the Treatment of Parkinson's Disease
LeWitt
NEJM 2008;359:2468-2476.
FULL TEXT  

Pharmacologic Management of Parkinson Disease: Choice of Initial Therapy in Early Disease
Chen and Pahwa
Journal of Pharmacy Practice 2008;21:244-253.
ABSTRACT  

Current Management of the Cognitive Dysfunction in Parkinson's Disease: How Far Have We Come?
Vale
Exp. Biol. Med. 2008;233:941-951.
ABSTRACT | FULL TEXT  

Unregulated Cytosolic Dopamine Causes Neurodegeneration Associated with Oxidative Stress in Mice
Chen et al.
J. Neurosci. 2008;28:425-433.
ABSTRACT | FULL TEXT  

Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease
The Parkinson Study Group PRECEPT Investigators
Neurology 2007;69:1480-1490.
ABSTRACT | FULL TEXT  

Validation of a Standardized Normalization Template for Statistical Parametric Mapping Analysis of 123I-FP-CIT Images
Kas et al.
JNM 2007;48:1459-1467.
ABSTRACT | FULL TEXT  

Gender differences in Parkinson's disease
Haaxma et al.
J. Neurol. Neurosurg. Psychiatry 2007;78:819-824.
ABSTRACT | FULL TEXT  

Risk factors for somnolence, edema, and hallucinations in early Parkinson disease
Biglan et al.
Neurology 2007;69:187-195.
ABSTRACT | FULL TEXT  

Optimized, Automated Striatal Uptake Analysis Applied to SPECT Brain Scans of Parkinson's Disease Patients
Zubal et al.
JNM 2007;48:857-864.
ABSTRACT | FULL TEXT  

New pharmacologic horizons in the treatment of Parkinson disease.
Bonuccelli and Del Dotto
Neurology 2006;67:S30-S38.
ABSTRACT | FULL TEXT  

Dopamine D3 receptor agonist delivery to a model of Parkinson's disease restores the nigrostriatal pathway and improves locomotor behavior.
Van Kampen and Eckman
J. Neurosci. 2006;26:7272-7280.
ABSTRACT | FULL TEXT  

Long-term 24-hour duodenal infusion of levodopa: outcome and dose requirements.
Nutt et al.
Neurology 2006;66:1611-1612.
FULL TEXT  

The need for neuroprotective therapies in Parkinson's disease: A clinical perspective
Poewe
Neurology 2006;66:S2-S9.
ABSTRACT | FULL TEXT  

Clinical trials aimed at detecting neuroprotection in Parkinson's disease
Hauser and Zesiewicz
Neurology 2006;66:S58-S68.
ABSTRACT | FULL TEXT  

Transcranial sonography and [123I]FP-CIT SPECT disclose complementary aspects of Parkinson's disease
Spiegel et al.
Brain 2006;129:1188-1193.
ABSTRACT | FULL TEXT  

Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Suchowersky et al.
Neurology 2006;66:976-982.
ABSTRACT | FULL TEXT  

PET Imaging of the Dopamine Transporter with 18F-FECNT: A Polar Radiometabolite Confounds Brain Radioligand Measurements
Zoghbi et al.
JNM 2006;47:520-527.
ABSTRACT | FULL TEXT  

Present and future drug treatment for Parkinson's disease
Schapira
J. Neurol. Neurosurg. Psychiatry 2005;76:1472-1478.
ABSTRACT | FULL TEXT  

Is Iterative Reconstruction an Alternative to Filtered Backprojection in Routine Processing of Dopamine Transporter SPECT Studies?
Koch et al.
JNM 2005;46:1804-1811.
ABSTRACT | FULL TEXT  

Diagnosis and Initial Management of Parkinson's Disease
Nutt and Wooten
NEJM 2005;353:1021-1027.
FULL TEXT  

Progression of Parkinson Disease: Are We Making Progress in Charting the Course?
Jankovic
Arch Neurol 2005;62:351-352.
FULL TEXT  

Nonlinear Progression of Parkinson Disease as Determined by Serial Positron Emission Tomographic Imaging of Striatal Fluorodopa F 18 Activity
Hilker et al.
Arch Neurol 2005;62:378-382.
ABSTRACT | FULL TEXT  

The role of radiotracer imaging in Parkinson disease
Ravina et al.
Neurology 2005;64:208-215.
ABSTRACT | FULL TEXT  

Imaging of dopaminergic dysfunction with [123I]FP-CIT SPECT in early-onset parkin disease
Varrone et al.
Neurology 2004;63:2097-2103.
ABSTRACT | FULL TEXT  

Levodopa and the Progression of Parkinson's Disease
The Parkinson Study Group
NEJM 2004;351:2498-2508.
ABSTRACT | FULL TEXT  

Initial Treatment of Parkinson Disease: Levodopa or Dopamine Agonists
Weiner
Arch Neurol 2004;61:1966-1969.
FULL TEXT  

Dopamine Agonists Modify the Course of Parkinson Disease
Stern
Arch Neurol 2004;61:1969-1971.
FULL TEXT  

The comparative effects of medical therapies for Parkinson's disease
Horn and Stern
Neurology 2004;63:S7-S12.
FULL TEXT  

Clinical trials of neuroprotection for Parkinson's disease
LeWitt
Neurology 2004;63:S23-S31.
FULL TEXT  

Loss of Dopamine Transporter Binding in Parkinson's Disease Follows a Single Exponential Rather Than Linear Decline
Schwarz et al.
JNM 2004;45:1694-1697.
ABSTRACT | FULL TEXT  

Biomarkers and Parkinson's disease
Michell et al.
Brain 2004;127:1693-1705.
ABSTRACT | FULL TEXT  

Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease: A 4-Year Randomized Controlled Trial
The Parkinson Study Group
Arch Neurol 2004;61:1044-1053.
ABSTRACT | FULL TEXT  

Reproducibility of 99mTc-TRODAT-1 SPECT Measurement of Dopamine Transporters in Parkinson's Disease
Hwang et al.
JNM 2004;45:207-213.
ABSTRACT | FULL TEXT  

Slowing Parkinson's disease progression: Recent dopamine agonist trials
Montgomery et al.
Neurology 2004;62:343-345.
FULL TEXT  

Neuroprotection in Parkinson Disease: Mysteries, Myths, and Misconceptions
Schapira and Olanow
JAMA 2004;291:358-364.
ABSTRACT | FULL TEXT  

New developments in levodopa therapy
LeWitt and Nyholm
Neurology 2004;62:S9-16.
ABSTRACT | FULL TEXT  

Treatments of Parkinson Disease: Circa 2003
Shults
Arch Neurol 2003;60:1680-1684.
ABSTRACT | FULL TEXT  

Clinical strategies to prevent and delay motor complications
Barone
Neurology 2003;61:S12-16.
ABSTRACT | FULL TEXT  

Present and future directions in the management of motor complications in patients with advanced PD
Olanow
Neurology 2003;61:S24-33.
FULL TEXT  

Neuroprotection in PD--A role for dopamine agonists?
Schapira
Neurology 2003;61:S34-42.
FULL TEXT  

Imaging the dopamine system to assess disease-modifying drugs: Studies comparing dopamine agonists and levodopa
Marek et al.
Neurology 2003;61:S43-48.
FULL TEXT  

Disease-modifying strategies and challenges in PD: Interactive breakout sessions
Schapira
Neurology 2003;61:S56-63.
FULL TEXT  

Neuroprotection in Parkinson Disease
Simpkins and Jankovic
Arch Intern Med 2003;163:1650-1654.
ABSTRACT | FULL TEXT  

Quantitative Accuracy of Dopaminergic Neurotransmission Imaging with 123I SPECT
Soret et al.
JNM 2003;44:1184-1193.
ABSTRACT | FULL TEXT  

Neuroprotective agents for clinical trials in Parkinson's disease: A systematic assessment
Ravina et al.
Neurology 2003;60:1234-1240.
ABSTRACT | FULL TEXT  

Update on Parkinson Disease
Siderowf and Stern
ANN INTERN MED 2003;138:651-658.
ABSTRACT | FULL TEXT  

Agonists vs levodopa in PD: The thrilla of whitha
Wooten
Neurology 2003;60:360-362.
FULL TEXT  

Slowing Parkinson's disease progression: Recent dopamine agonist trials
Ahlskog
Neurology 2003;60:381-389.
ABSTRACT | FULL TEXT  

Initial agonist treatment of Parkinson disease: A critique
Albin and Frey
Neurology 2003;60:390-394.
ABSTRACT | FULL TEXT  

Drugs for Parkinson's disease
Lees
J. Neurol. Neurosurg. Psychiatry 2002;73:607-610.
FULL TEXT  

Brain Imaging to Assess the Effects of Dopamine Agonists on Progression of Parkinson Disease
Ahlskog et al.
JAMA 2002;288:311-313.
FULL TEXT  

Basic Science and Translational Research in JAMA
Fontanarosa and DeAngelis
JAMA 2002;287:1728-1728.
FULL TEXT  

Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Suchowersky et al.
Neurology 2006;66:976-982.
ABSTRACT | FULL TEXT