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）： 左旋多巴引起的运动障碍（盖）是大多数帕金森氏病（PD）发生的非自愿性，异常运动，这是由于长期使用最有效的有症状药物Levodopa（LD）而发生的。盖子的范围从微妙，不引人注目，到标记和禁用。令人惊讶的是，盖子的治疗方法很少，包括阿甘丹丁和深脑刺激。在许多情况下，阿曼塔丁的耐受性不佳，要么提供不足的利益，而且只有少数是适当的手术候选者。鉴于发现二十六烷酸（大脑中最丰富的omega-3脂肪酸）延迟发作并降低了两个不同动物模型中发育不良的严重程度，这是一项docosahexanoic（DHA）的试验，PD受试者在PD受试者中的一部分，以预防其药物治疗方案，以防止其药物的进展，以防止其速度或慢速进行。在进行大型试验之前，需要进行有关DHA在PD受试者中安全性和耐受性的初步数据，并且该数据的收集是该试点项目建议的主要结果。 30名尚未使用Levodopa但即将开始的受试者将被随机分为DHA或安慰剂。安全实验室测试，不良事件监测，DHA血浆和CSF水平以及合规性/受试者保留将收集结果。此外，将收集有关发生率修改的初步数据，并在两个治疗组之间进行比较。该信息将有助于计算适当的样本量和治疗期，以进行更大的确定性研究。当等离子体左旋多巴水平足够高以引起抗Parkinsonian益处时，运动障碍都表现出绝大多数，而当左旋多巴水平下降到阈值以下时，则会减少或停止。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。在第0、6、6、24、52、104周给予受试者的两个小时的左旋多巴周期期间，会发生运动障碍测量。预计，有很大比例的受试者将在两年观察期内表现出发育不良期，因为先前的研究使用最客观的研究使用最客观的研究手段，该手段使用衡量运动障碍报告率在67％或更高的时间内使用了67％或更高的levopa。测量该中心开发的运动障碍的仪器将被用作额外的结果，并有望比临床评级量表的黄金标准方法更准确地测量运动障碍和具有更高的敏感性。通过该试点项目的结论，将确定安全性和耐受性，受试者保留和合规性，血浆/CSF的DHA给药水平。可以测量运动能力发育的趋势。这将提供所需的背景信息，以进行DHA的未来更大的试验，以防止PD中的运动障碍。