Reducing Dyskinesia in Parkinson Disease with Omega-3 Fatty Acids

使用 Omega-3 脂肪酸减少帕金森病的运动障碍

• 批准号: 8453246
• 负责人: Kathryn Anne Chung
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453246
• 关键词: Acids; Activities of Daily Living; Adverse drug effect; Adverse effects; Adverse event; Affect; Amantadine; Animal Model; Animals; Area Under Curve; Brain; Caring; Chronic; Clinical; Data; Data Collection; Deep Brain Stimulation; Development; Disease; Drops; Drug-Induced Dyskinesia; Dyskinetic syndrome; Education; Fingers; Fish Oils; Future; Gold; Healthcare Systems; Hour; Human; Incidence; Infusion procedures; Laboratories; Levodopa; Literature; Longitudinal Studies; Macaca; Measurement; Measures; Medical; Mental Depression; Methods; Minority; Modification; Monitor; Motor; Movement; Natural History; Neurodegenerative Disorders; Neurologic; Omega-3 Fatty Acids; Operative Surgical Procedures; Outcome; Parkinson Disease; Parkinsonian Disorders; Patients; Pharmaceutical Preparations; Pilot Projects; Placebos; Plasma; Prevalence; Quality of life; Randomized; Randomized Controlled Trials; Regimen; Reporting; Research; Research Design; Rodent Model; Safety; Sample Size; Severities; Speed; Techniques; Testing; Time; United States; Veterans; abnormal involuntary movement; dietary supplements; drug standard; foot; improved; instrument; neurotransmission; older men; pre-clinical; prevent; primary outcome; prospective; treatment duration; trend

DESCRIPTION (provided by applicant): Levodopa induced dyskinesias (LID) are involuntary, abnormal movements that occur in most patients with Parkinson disease(PD) as a consequence of chronic use of the most effective symptomatic drug, levodopa (LD). LID can range from subtle and unobtrusive to marked and disabling. There are surprisingly few treatments for LID, including amantadine and deep brain stimulation. In many instances, amantadine is either poorly tolerated, or provides inadequate benefit, and only a small minority are appropriate candidates for surgery. Given the finding that docosahexanoic acid (the most abundant omega-3 fatty acid in the brain), delays the onset and reduces the severity of dyskinesia in two different animal models of LID, a trial of docosahexanoic acid (DHA) in PD subjects about to start LD as part of their drug regimen, to prevent or slow the progression of LID is warranted. Prior to embarking on a large trial, preliminary data about safety and tolerability of DHA in PD subjects is needed, and collection of this data is the primary outcome of this pilot project proposal. 30 subjects who have not yet used levodopa, but are about to begin it will be randomized to daily DHA or placebo. Safety laboratory testing, adverse event monitoring, DHA plasma and CSF levels as well as compliance/subject retention will be outcomes collected. In addition, preliminary data about modification of incidence rates will be collected and compared between the two treatment groups. This information will aid in calculating an appropriate sample size and treatment period for a larger definitive future study. Dyskinesia manifests overwhelmingly when plasma levodopa levels are high enough to cause anti-parkinsonian benefits, and lessens or stops when levodopa levels drop below a threshold. Thus, the subject's dyskinesia measurements must occur during a levodopa administration period. Dyskinesia measurement will occur during a two-hour levodopa cycle administered to subjects at weeks 0, 6, 24, 52, 104. It is expected that a good proportion of subjects will manifest dyskinesia within the two-year observation period, as previous studies using the most objective means to measure dyskinesia report incidence rates of 67% or greater within the first year of levodopa use. An instrument to measure dyskinesia developed by this center will be used as an additional outcome, and is expected to measure dyskinesia more accurately and with greater sensitivity than the gold standard methods of clinical rating scales. By conclusion of this pilot project, the safety and tolerability, subject retention and compliance, plasma/CSF levels of DHA administration will be determined. Trends in dyskinesia development may be measured. This will provide the needed background information to proceed with a future larger trial of DHA to prevent dyskinesia in PD.

描述（由申请人提供）： 左旋多巴诱发的运动障碍 (LID) 是大多数帕金森病 (PD) 患者因长期使用最有效的对症药物左旋多巴 (LD) 而发生的不自主、异常运动。 LID 的范围可以从微妙的、不引人注目的到明显的和致残的。令人惊讶的是，LID 的治疗方法很少，包括金刚烷胺和深部脑刺激。在许多情况下，金刚烷胺要么耐受性差，要么提供的益处不足，并且只有一小部分人适合手术。鉴于在两种不同的 LID 动物模型中发现二十二碳六烯酸（大脑中最丰富的 omega-3 脂肪酸）可以延缓运动障碍的发作并减轻运动障碍的严重程度，一项针对 PD 受试者的二十二碳六烯酸 (DHA) 试验即将开始 LD 作为药物治疗的一部分，以预防或减缓 LID 的进展是有必要的。在开始大规模试验之前，需要有关 DHA 在 PD 受试者中的安全性和耐受性的初步数据，收集这些数据是该试点项目提案的主要成果。 30 名尚未使用左旋多巴但即将开始使用的受试者将被随机分配每日服用 DHA 或安慰剂。安全实验室测试、不良事件监测、DHA 血浆和脑脊液水平以及依从性/受试者保留率将被收集。此外，还将收集并比较两个治疗组之间发生率变化的初步数据。这些信息将有助于计算适当的样本量和治疗周期，以进行更大的确定性未来研究。当血浆左旋多巴水平足够高以产生抗帕金森病益处时，运动障碍明显表现出来，而当左旋多巴水平降至阈值以下时，运动障碍减轻或停止。因此，受试者的运动障碍测量必须在左旋多巴给药期间进行。运动障碍测量将在第 0、6、24、52、104 周对受试者进行两小时左旋多巴周期期间进行。预计很大一部分受试者将在两年观察期内表现出运动障碍，正如之前的研究使用测量运动障碍的最客观方法报告称，在使用左旋多巴的第一年内，其发病率为 67% 或更高。该中心开发的一种测量运动障碍的仪器将作为额外的结果，预计将比临床评定量表的金标准方法更准确、更灵敏地测量运动障碍。通过该试点项目的结束，将确定 DHA 给药的安全性和耐受性、受试者保留和依从性、血浆/脑脊液水平。可以测量运动障碍发展的趋势。这将为未来进行更大规模的 DHA 试验提供所需的背景信息，以预防 PD 运动障碍。