Valerian for Sleep Disturbance in Healthy Older Adults

描述(申请人提供)：睡眠障碍在老年人中非常常见。多达40%的老年人抱怨睡眠问题，包括无法快速入睡、夜间频繁醒来或清晨醒来。未经治疗的睡眠障碍可能会增加患抑郁症和早期死亡的风险。老年人经常使用处方催眠药和非处方药作为睡眠辅助药物，尽管观察到这些药物进一步扰乱了睡眠模式，并有不良副作用。草药作为膳食补充剂已经相当受欢迎，并可能在未来几十年被越来越多的成年人使用。替代草药，如Valerian，2001年在美国最畅销的草药产品中跻身前20名，具有改善睡眠的潜力，但其有效性需要在老年人中确定。缬草含有多种化合物，包括戊酸及其衍生物。有关安定成分的药代动力学性质还没有报道，也没有关于安定成分与客观睡眠措施有关的药代动力学性质的任何已知。一篇有限的小样本安慰剂对照试验的文献表明，安定可以改善睡眠，并且副作用非常低。这项初步研究的具体目的是确定推荐剂量的安定改善睡眠的效果，并描述其在主诉睡眠障碍的老年人中的药代动力学特性。我们已经建立了一种测定戊酸的方法，并将描述连续治疗两周后单次给药和稳定状态下安定的药代动力学，并将多导睡眠图所显示的改善睡眠的效果与安定PK联系起来。我们的工作假设是，Valerian在每日夜间服药两周后(慢性)会改善睡眠，但不太可能在单次服药后改善睡眠(急性)。这项设计将是一项单组、双盲、安慰剂对照的交叉试验，对象为20名年龄在55岁至80岁之间、相对健康的老年女性和男性。我们期望这项研究结果将提供初步数据，支持一项关于安定对老年人主观和客观睡眠质量影响的大型随机临床试验。

DESCRIPTION (provided by applicant): Sleep disturbances are very common in the elderly. As many as 40% of older adults complain about sleep problems, including inability to fall asleep quickly, frequent nocturnal awakenings, or early morning awakenings. Untreated sleep disturbances may increase the risk for depression and early mortality. Older adults frequently use prescription hypnotic and over-the-counter medications as sleep aids, despite observations these drugs further disrupt sleep patterns and have untoward side effects. Herbal medicines as dietary supplements are already quite popular and likely to be used by increasing numbers of adults in the next few decades. Alternative herbal medicines, such as valerian, which was in the top 20 best selling herbal products in the United States in 2001, have the potential to enhance sleep but their efficacy needs to be established in older adults. Valerian contains a variety of compounds including valerenic acid and its derivatives. The pharmacokinetic properties of the valerian constituents have not been reported and there is nothing known about the pharmacokinetic properties of valerian constituents in relation to objective sleep measures. A limited literature of small-sample placebo-controlled trials suggests that valerian may improve sleep and has a very low rate of side effects. The specific aims of this preliminary study are to determine the sleep enhancing effects of a recommended dose of valerian and to describe its pharmacokinetic properties in older adults with a complaint of sleep disturbance. We have developed an assay for valerenic acid and will describe the pharmacokinetics of valerian after a single dose and at steady state following two weeks of continuous treatment and relate the sleep enhancing effects as shown by polysomnography to valerian PK. Our working hypothesis is that valerian will enhance sleep after two weeks of daily nighttime dosing (chronic), but is not likely to enhance sleep after a single dose (acute). The design will be a single group, double-blind, placebo controlled cross-over trial in 20 relatively healthy older adult women and men, 55 to 80 years old. We expect the study outcomes will provide preliminary data in support of a large randomized clinical trial of valerian effects on subjective and objective sleep quality in older adults.