Earlier vs. Later Levodopa in Parkinson's Disease

描述(申请人提供)：这是一种双盲、安慰剂对照、 采用平行设计的多中心临床试验来确定 左旋多巴对帕金森病(PD)自然病史的影响(如果有的话)。 本质上，存在一个严重的问题，即左旋多巴，最重要的 而强大的药物可用于治疗帕金森病的症状，加速潜在的 尽管对症状有好处，但疾病的进展还是 没有效果，甚至会减慢进展速度。该设计是一种 左旋多巴与安慰剂配伍治疗帕金森病患者的剂量反应试验 最早阶段，即症状非常轻微以至于有症状的阶段 不需要治疗。登记的受试者被分配给安慰剂或以下一种 三剂(12.5/50，25/100，50/200 mg，tid)卡比多巴/左旋多巴 花40周(9个月)，然后是两周的洗涤期。没有其他人了 这项研究允许使用抗帕金森药物。在冲刷结束时 时段失明的主要评分员，谁在基线上检查了主题，谁 在接下来的42周内没有与受试者有过其他接触，重新检查 病人。主要的结果变量是严重程度的变化率。 根据剂量-反应曲线，四个治疗臂中的帕金森病。严重程度为 使用统一的帕金森氏病评定量表(UPDRS)进行临床测量。 盲目的机构治疗调查员在整个过程中评估受试者 研究和调整剂量或添加特定解毒剂药物的频率 克服临床判定为研究用药的并发症 必填项。在试验期间，不会公开添加任何有症状的抗PD药物。 还有一些次要结果变量：监测 左旋多巴的长期和短期益处，研究疲劳 帕金森病，左旋多巴对抑郁的影响，咖啡因对帕金森病的影响，以及 左旋多巴不良反应的发展。从这项研究中获得的知识 将解决患者、家属和临床医生最关心的问题， 也就是说，只要临床可行，左旋多巴就应该被推迟，或者被用作 越早越好。美国国立卫生研究院于1月1日开始为这项临床试验提供资金， 1998年，计划于2000年12月31日竣工。我们不能 在这个时间框架内完成这项临床试验， 申请，我们要求延长截止日期，并追加 努力完成这项研究。

DESCRIPTION (provided by applicant): This double-blind, placebo-controlled, parallel-design multi-center clinical trial was developed to determine the impact, if any, of levodopa on the natural history of Parkinson's disease (PD). In essence, there is a serious question whether levodopa, the most important and powerful drug available to treat the symptoms of PD, hastens the underlying progression of the disease in spite of its symptomatic benefit or whether it has no effect, or even slows the rate of progression. The design is that of a dose-response test of levodopa and matching placebo in patients with PD at its earliest stage, i.e., a stage where the symptoms are so mild that symptomatic treatment is not required. Enrolled subjects are assigned placebo or one of three doses (12.5/50, 25/100, 50/200 mg tid) of carbidopa/levodopa which they take for 40 weeks (9 months), followed by a two-week washout period. No other anti-Parkinson medication is allowed in the study. At the end of the washout period the blinded Primary Rater, who examined the subject at baseline and who has had no other contact with the subject over the next 42 weeks, re-examines the patient. The primary outcome variable is the rate of change of severity of PD in the four treatment arms based on a dose-response curve. Severity is measured clinically using the Unified Parkinson's Disease Rating Scale (UPDRS). The blinded institutional treating investigator evaluates subjects throughout the study and adjusts the frequency of dosings or adds 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. There are a number of secondary outcome variables as well: monitoring the longduration and the short-duration benefit of levodopa, studying fatigue in PD, the effect of levodopa on depression, the effect of caffeine on PD, and the development of adverse effects of levodopa. 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. NIH funding for this clinical trial began on January 1, 1998, and is scheduled to be completed on December 3 1, 2000. We are not able to complete this clinical trial within this time frame, and with this application we are requesting an extension of the deadline with additional ftinding to complete the study.