EARLIER VS LATER L DOPA IN PARKINSONS DISEASE

左旋多巴是目前临床上最有效、应用最广泛的药物， 帕金森病（PD）的症状和体征。近年来， 越来越多的科学报告发现左旋多巴和多巴胺 在体外和体内对儿茶酚胺能神经元都有毒性 PD动物模型。 这引起了越来越多的关注， 神经学家和神经科学家认为左旋多巴治疗可能 这促使神经学家和神经科学家越来越关注 左旋多巴治疗可能会加速 黑质多巴胺能神经元的变性， 的PD。由于左旋多巴是用于治疗PD的主要药物， 重要的是确定左旋多巴是否会加重PD。 这项研究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 一方面，早期引入左旋多巴可能导致立即出现症状， 效益和更高的生活质量。 或者，如果左旋多巴 加速多巴胺能细胞损失的进展，它将更快地导致 到晚期疾病，最终未能响应左旋多巴或 其他抗PD药物 这项对照临床试验的主要目的是 是为了回答这个问题：早期使用左旋多巴 为PD患者提供更好的生活质量， PD的潜在进展？ 我们将招募360例早期未经治疗的PD患者， 随机、安慰剂对照、双盲、多中心临床 审判 受试者将被随机分配至四个相同大小的 治疗组：卡比多巴/左旋多巴（12.5/50、25/100、50/200 mg tid）和 匹配的安慰剂。 他们将接受9个月的治疗， 在减少过早戒断方面具有临床意义和可行性 从审判中。主要结局变量是PD临床发生率 基于剂量-反应曲线的进展，比较基线与治疗后 治疗措施。 PD进展将通过以下指标的变化来衡量： 未治疗组和未治疗组之间的总统一帕金森病评定量表（UMRS） 基线和最终访视。 最后一次访视将在14天后进行 9个月后退出实验性治疗 后续治疗。 设盲的机构主要评估者， 否则将不参与临床评价或药物治疗 试验期间的调整，将执行这些基线和最终 联合国难民事务高级专员办事处评价。设盲的机构治疗研究者将 每3个月对受试者进行一次评估，并可能调整 剂量或添加特定的解毒药物，以克服并发症， 当判断为临床需要时，给予研究药物。 无症状性抗- PD药物将在试验期间公开添加。获得的消息 这项研究将解决病人、家属、 和临床医生，也就是说，应该推迟左旋多巴，只要临床上 或者尽早使用。

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.