Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS: Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. INTERVENTION: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. CONCLUSIONS: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.

Reaction time and movement time after embryonic cell implantation in Parkinson disease.

BACKGROUND: Embryonic nigral cell implants are a novel treatment for Parkinson disease (PD). Reaction time (RT) and movement time (MT) analysis, validated quantitative measures of premovement neural processing and motor execution, can be used as objective physiological markers of motor performance in PD. OBJECTIVES: To gauge the change in motor performance in patients with PD who received implants, and to determine whether the physiological findings correlate with clinical outcome measures after transplantation. DESIGN: Double-blind, placebo-controlled trial. Patients Forty patients with levodopa-responsive, Hoehn and Yahr stage III or greater PD. INTERVENTIONS: Random assignment to embryonic tissue implants or placebo (sham) operation. MAIN OUTCOME MEASURES: Combined RT + MT scores measured preoperatively and at 4 and 12 months postoperatively in the "off" state. RESULTS: The difference in mean RT + MT scores between the sham and implant groups was statistically significant (P =.005) and was greatest in those 60 years or older (P =.003). Changes correlated with Unified Parkinson's Disease Rating Scale off scores at 4 (r = 0.87, P =.001) and 12 (r = 0.75, P =.01) months in those younger than 60 years. There was a significant deterioration in the sham surgery group at 12 months (P =.03) that was thought to be due to worsening in subjects 60 years and older (P<.001). CONCLUSIONS: The physiological measures detected significant changes in patients undergoing embryonic nigral cell implants and correlated directly with clinical outcome measures. Comprehensive analyses of RT paradigms can document subtle changes in motor performance over time, making them useful outcome measures in therapeutic trials of PD. These findings support further research into nigral cell implantation for PD.

Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial.

CONTEXT: This study was part of a large double-blind sham surgery-controlled trial designed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson's disease. This portion of the study investigated the quality of life (QOL) of participants during the 1 year of double-blind follow-up. OBJECTIVES: To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment (the type of surgery patients thought they received). DESIGN: Participants were randomly assigned to receive either the transplant or sham surgery. Reported results are from the 1-year double-blind period. SETTING: Participants were recruited from across the United States and Canada. Assessment and surgery were conducted at 2 separate university medical centers. PARTICIPANTS: A volunteer sample of 40 persons with idiopathic Parkinson's disease participated in the transplant ("parent") study, and 30 agreed to participate in the related QOL study: 12 received the transplant and 18 received sham surgery. INTERVENTIONS: Interventions in the parent study were transplantation and sham brain surgery. Assessments of QOL were made at baseline and 4, 8, and 12 months after surgery. MAIN OUTCOME MEASURES: Comparison of the actual transplant and sham surgery groups and the perceived treatment groups on QOL and medical outcomes. We also investigated change over time. RESULTS: There were 2 differences or changes over time in the transplant and sham surgery groups. Based on perceived treatment, or treatment patients thought they received, there were numerous differences and changes over time. In all cases, those who thought they received the transplant reported better scores. Blind ratings by medical staff showed similar results. CONCLUSIONS: The placebo effect was very strong in this study, demonstrating the value of placebo-controlled surgical trials.