EARLIER VS LATER L DOPA IN PARKINSONS DISEASE

左旋多巴是目前最有效、应用最广泛的药物。 帕金森氏病(PD)的体征和症状。最近几年，一个 越来越多的科学报告发现左旋多巴和多巴胺 对体外和体内的儿茶酚胺能神经元均有毒性 帕金森病的动物模型。这引发了人们越来越多的担忧 神经学家和神经学家认为，左旋多巴治疗可能是 加速了神经学家和神经学家日益增长的担忧 左旋多巴治疗可能会加速潜在的进行性 黑质多巴胺能神经元变性是其病理特征 警局的。由于左旋多巴是治疗帕金森病的主要药物，它是 重要的是确定左旋多巴是否会加重帕金森病。 这项研究中的调查人员有很大的不确定性 (临床平衡)关于左旋多巴可能的毒性。一对一 另一方面，早期使用左旋多巴可能会导致立即出现症状 效益和更高的生活质量。或者，如果左旋多巴 加速多巴胺能细胞的丧失，它会更快地导致 对晚期疾病，最终对左旋多巴或 其他抗帕金森病药物。这项对照临床试验的主要目标是 是为了回答这个问题：左旋多巴的早期引入 为PD患者提供更高的生活质量，还是提高了 帕金森病的潜在进展？ 我们将招募360名早期未经治疗的帕金森病患者参加 随机、安慰剂对照、双盲、多中心临床研究 审判。受试者将被随机分成四个同等大小的人 治疗武器：卡比多巴/左旋多巴(12.5/50，25/100，50/200 mg，tid)和 与之匹配的安慰剂。他们将接受9个月的治疗，在此期间 对于最大限度地减少过早戒断具有临床意义和可行性 从审判中拿出来的。主要的结果变量是帕金森病的临床发生率 基于剂量-反应曲线的进展，比较基线和治疗后 治疗措施。PD进展将通过以下变化来衡量 总统一帕金森病评定量表(UPDRS)在未治疗之间 基线和最终访问。最后一次访问将在14天后进行 在9个月后停止试验性治疗 随访治疗情况。盲目的机构主要评价者，谁 否则不会参与临床评估或药物治疗 在试验期间的调整，将执行这些基线和最终 UPDRS评价。盲目的机构治疗调查员将 每隔3个月对受试者进行评估，并可能调整 剂量或添加特定解毒剂药物以克服以下并发症 在判断为临床需要时研究药物。无症状性抗- 帕金森病药物将在试验期间公开添加。从以下方面获得的知识 这项研究将解决患者家属最普遍关心的问题 和临床医生，即左旋多巴是否应该被推迟到临床上 可行的或尽早使用的。

Levodopa is the most effective and widely used drug in ameliorating the signs and symptoms of Parkinson's disease (PD). In recent years, an increasing number of scientific reports find both levodopa and dopamine to be toxic to catecholaminergic neurons both in vitro and in vivo animal models of PD. This has led to a growing concern among neurologists and neuroscientists that levodopa treatment may be hastening the growing concern among neurologists and neuroscientists that levodopa treatment may be hastening the underlying progressive degeneration of nigral dopaminergic neurons, the pathological hallmark of PD. Since levodopa is the major drug used to treat PD, it is important to determine whether levodopa does or does not aggravate PD. The investigators in this study have a great deal of uncertainty (clinical equipoise) about the possible toxicity of levodopa. On one hand, early introduction of levodopa could lead to immediate symptomatic benefit and a higher quality of life. Alternatively, if levodopa hastens progression of dopaminergic cell loss, it will more rapidly lead to advanced disease, which ultimately fails to respond to levodopa or other anti-PD drugs. The main goal of this controlled clinical trial is to answer the question: does the early introduction of levodopa provide improved quality of life to PD patients or does it enhance the underlying progression of PD? We will enroll 360 patients with early, untreated PD into this randomized, placebo-controlled, double blinded, multi-center clinical trial. Subjects will be randomized into one of four equally sized treatment arms: carbidopa/levodopa (12.5/50, 25/100, 50/200 mg tid) and matching placebo. They will be treated for 9 months, a duration which is clinically meaningful and feasible in minimizing premature withdrawal from the trial. The primary outcome variable is the rate of PD clinical progression based on a dose-response curve, comparing baseline to post- treatment measures. PD progression will be measured by the change in total Unified Parkinson's Disease Rating Scale (UPDRS) between untreated baseline and final visit. The final visit will take place 14 days after withdrawal from experimental treatments subsequent to 9 months of follow-up on treatment. The blinded institutional primary rater, who will otherwise not be involved in clinical evaluations or medication adjustments during the trial, will perform these baseline and final UPDRS evaluations. The blinded institutional treating investigator will evaluate subjects at 3-month intervals and may adjust the frequency of dosings or add specified antidote drugs to overcome complications from study drug when judged to be clinically required. No symptomatic anti- PD drug will be openly added during the trial. Knowledge gained from this study will address the most common concern of patients, families and clinicians, namely should levodopa be delayed as long as clinically feasible or be used as early as possible.