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Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. 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. [ed: my impression from reading the earlier literature is that while levodopa can be toxic in vitro, it is not toxic in vivo; and that this has been proven conclusively; in fact the theory is now being evaluated that levodopa may be neuroprotective] 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 2beta-carboxymethoxy-3beta(4-iodophenyl)tropane (beta-CIT) labeled with iodine 123. DESIGN: Substudy of a parallel-group, double-blind randomized clinical trial. SETTING AND PATIENTS: 82 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 [(123)I]beta-CIT uptake after 46 months. The percentage changes and absolute changes in striatal, putamen, and caudate [(123)I]beta-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) [(123)I]beta-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 [(123)I]beta-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 [(123)I]beta-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 [(123)I]beta-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. [ed: this conclusion says nothing definitive about pramipexole, inmho. it simply says we need to find a better way of measuring these things] JAMA 2002 Apr 3;287(13):1653-61 Parkinson Study Group; Marek K, Seibyl J, Shoulson I, Holloway R, Kieburtz K, McDermott M, Kamp C, Shinaman A, Fahn S, Lang A, Weiner W, Welsh M CALM-PD-CIT, The Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA [log in to unmask] PMID: 11926889 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11926889&dopt=Abstract janet paterson: an akinetic rigid subtype, albeit perky, parky pd: 55/41/37 cd: 55/44/43 tel: 613 256 8340 email: [log in to unmask] smail: 375 Country Street, Almonte, Ontario, Canada, K0A 1A0 a new voice: http://www.geocities.com/janet313/ ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn