OMEGA-3 FATTY ACIDS IN BIPOLAR DISORDER PROPHYLAXIS

OMEGA-3 脂肪酸在双相情感障碍预防中的作用

• 批准号: 6375417
• 负责人: ANDREW L STOLL
• 金额: $ 50.38万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375417
• 关键词: behavioral /social science research tag; biomarker; bipolar depression; blood chemistry; brain imaging /visualization /scanning; clinical research; clinical trials; disease /disorder prevention /control; drug screening /evaluation; drug tolerance; human subject; human therapy evaluation; longitudinal human study; marine animal oil; mental disorder chemotherapy; mental disorder prevention; niacin; nuclear magnetic resonance spectroscopy; omega 3 fatty acid; pharmacokinetics; placebos; relapse /recurrence; therapy compliance; transdermal drug delivery; unsaturated fatty acids

The purpose of the proposed clinical trial is to assess the efficacy of omega-3 fatty acids (03FA) in preventing recurrence in patients with bipolar disorder, type 1. Omega-3 fatty acids from fish oil (a mixture of docosahexanoic (DHA) and eicosapentanoic (EPA) acids), are polyunsaturated lipids which inhibit intracellular signal transduction in a manner comparable to lithium and divalproex, 2 drugs with efficacy in bipolar disorder. An initial 4 month, double-blind, placebo-controlled, add-on study of 03FA treatment in 30 recently ill bipolar patients revealed that the omega-3 treated group had a significantly greater duration of remission compared to the placebo group (p = 0.002 Mantel-Cox). 03FA are non-toxic, essential dietary lipids, and there were few side-effects to the 03FA treatment. This initial indication of efficacy, combined with the need for safe and effective prophylactic treatments for bipolar disorder, warrant undertaking a larger and more rigorously designed 1-year prophylactic study, to be completed over a 3-4 year funding period. In the proposed 2-site primary study, 120 outpatients with bipolar disorder, type I, will be randomly assigned to receive add-on treatment with 03FA or placebo, for one year. The primary goal of this study is to assess the prophylactic effects of 03FA in a cohort of bipolar patients with a relatively high risk of recurrence. In contrast to the pilot study, the proposed trial will tightly control the baseline clinical state and concurrent pharmacotherapy of the subjects to provide a more homogeneous bipolar population. This will be accomplished through a lead-in and stabilization phase where patients will be gradually shifted to receive a standardized regimen (lithium or divalproex). Only subjects who are euthymic or subsyndromal at the end of the lead-in period will be eligible for the 1-year prophylactic study. The following biological markers will be examined as measures of compliance with the study protocol and/or as possible predictors of response to 03FA: 1. Plasma and erythrocyte fatty acid content. 2. The niacin skin patch test (a possible marker of in vivo omega-3 fatty acid activity). 3. Preliminary development of methods to noninvasively measure the 03FA content in brain using C13 magnetic resonance spectroscopy. If 03FA are indeed effective mood stabilizers for bipolar disorder, this project would provide additional evidence of aberrant signal transduction mechanisms in the pathophysiology of bipolar disorder, and may herald the advent of a new class of rationally designed mood stabilizing drugs.

拟议的临床试验的目的是评估omega-3脂肪酸（03FA）在预防1型双相情感障碍患者复发中的功效。来自鱼油的Omega-3脂肪酸（二十二碳己酸（DHA）和二十碳五烯酸（EPA）的混合物）是一种多不饱和脂质，其抑制细胞内信号转导的方式与锂和双丙戊酸相当，这两种药物对双相情感障碍有效。对30名新近患病的双相情感障碍患者进行了为期4个月的双盲、安慰剂对照、附加研究，结果显示，与安慰剂组相比，omega-3治疗组的缓解持续时间明显更长（p = 0.002）。03FA是无毒的，必需的膳食脂质，并且对03FA治疗几乎没有副作用。这一初步疗效指标，加上对双相情感障碍安全有效预防性治疗的需求，有必要开展一项规模更大、设计更严格的1年预防性研究，在3-4年的资助期内完成。在拟议的2点初步研究中，120名I型双相情感障碍门诊患者将被随机分配接受为期一年的03FA或安慰剂的附加治疗。本研究的主要目的是评估03FA在复发风险相对较高的双相患者队列中的预防作用。与试点研究相反，拟议的试验将严格控制受试者的基线临床状态和同期药物治疗，以提供更均匀的双相人群。这将通过引入和稳定阶段来实现，患者将逐渐转向接受标准化方案（锂或双丙戊酸）。只有在导入期结束时处于健康或亚综合征状态的受试者才有资格参加为期1年的预防研究。将检查以下生物标记物，作为遵守研究方案的措施和/或作为对03FA: 1反应的可能预测因素。血浆和红细胞脂肪酸含量。2. 烟酸皮肤贴片试验（体内omega-3脂肪酸活性的可能标志）。3. C13磁共振波谱法无创性测定脑内03FA含量的初步研究。如果03FA确实是双相情感障碍的有效情绪稳定剂，该项目将为双相情感障碍病理生理中的异常信号转导机制提供额外的证据，并可能预示着一类新的合理设计的情绪稳定药物的出现。