Earlier vs. Later Levodopa in Parkinson's Disease

描述（由申请人提供）：这是一项双盲、安慰剂对照、 开发了平行设计的多中心临床试验，以确定 左旋多巴对帕金森病（PD）自然病程的影响（如果有的话）。 从本质上讲，有一个严重的问题，是否左旋多巴，最重要的 和强大的药物可用于治疗PD的症状，加速潜在的 疾病的进展，尽管它的症状的好处，或是否 没有效果，甚至减缓了进展的速度。设计是一个 左旋多巴和匹配安慰剂在PD患者中的剂量反应试验 最早期，即，一个阶段，症状非常轻微， 不需要治疗。入组的受试者被分配安慰剂或以下之一 三个剂量（12.5/50、25/100、50/200 mg tid）的卡比多巴/左旋多巴， 服用40周（9个月），然后是两周的洗脱期。没有其他 研究中允许使用抗帕金森药物。在淘汰赛结束时 设盲的主要评估者，在基线时检查受试者， 在接下来的42周内与受试者没有其他接触，重新检查 病人主要结果变量是严重程度的变化率， 基于剂量-反应曲线的4个治疗组的PD。严重程度 使用统一帕金森病评定量表（UnifiedParkinson 'sDiseaseRatingScale，简称PDRS）进行临床测量。 设盲的机构治疗研究者在整个过程中评价受试者 研究并调整给药频率或添加特定的解毒药物 在临床上被判定为 必需的.试验期间不公开增加对症抗PD药物。 还有一些次要结果变量：监测 长期和短期的左旋多巴的好处，研究疲劳， 左旋多巴对抑郁症的影响，咖啡因对PD的影响， 左旋多巴的副作用。从本研究中获得的知识 将解决患者、家属和临床医生最常见的问题， 也就是说，左旋多巴是否应该在临床上可行的情况下延迟使用，或者 越早越好。NIH对这项临床试验的资助始于1月1日， 工程预计于二零零零年十二月三十一日完成。我们无法 在这个时间范围内完成这项临床试验， 申请我们要求延长截止日期与额外的 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.