Valerian for Sleep Disturbance in Healthy Older Adults

描述（申请人提供）：睡眠障碍在老年人中很常见。多达40%的老年人抱怨睡眠问题，包括无法快速入睡、频繁夜间醒来或清晨醒来。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物作为助眠药，尽管观察到这些药物会进一步扰乱睡眠模式并产生不良副作用。草药作为膳食补充剂已经相当受欢迎，在未来几十年可能会被越来越多的成年人使用。替代草药，如缬草，是2001年美国最畅销的20种草药产品之一，具有增强睡眠的潜力，但其功效需要在老年人中得到证实。缬草含有多种化合物，包括戊酸及其衍生物。缬草成分的药代动力学特性尚未被报道，也没有任何关于缬草成分的药代动力学特性与客观睡眠测量的关系。有限的小样本安慰剂对照试验文献表明，缬草可以改善睡眠，而且副作用率很低。本初步研究的具体目的是确定推荐剂量缬草的睡眠增强作用，并描述其在抱怨睡眠障碍的老年人中的药代动力学特性。我们开发了一种测定缬草酸的方法，并将描述单剂量缬草和连续治疗两周后稳定状态下缬草的药代动力学，并将多导睡眠图显示的增强睡眠效果与缬草PK联系起来。我们的工作假设是，每天夜间服用缬草两周后会增强睡眠（慢性），但单剂量缬草不太可能增强睡眠（急性）。该设计将是一项单组、双盲、安慰剂对照的交叉试验，在20名相对健康的老年男性和女性中进行，年龄在55至80岁之间。我们期望研究结果将为缬草对老年人主观和客观睡眠质量影响的大型随机临床试验提供初步数据支持。

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.