Targeting Circadian and Cognitive Dysfunction in Bipolar Disorder with Modafinil

用莫达非尼治疗双相情感障碍的昼夜节律和认知功能障碍

• 批准号: 8725233
• 负责人: Katherine Elizabeth Burdick
• 金额: $ 25.43万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-22 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725233
• 关键词: Acute; Address; Adult; Adverse effects; Adverse event; Affective; Affective Symptoms; Amphetamines; Animal Model; Attention; Biological Assay; Biological Clocks; Biological Rhythm; Bipolar Disorder; Bipolar I; Chronic; Chronic Phase; Circadian Rhythms; Clinical; Clinical Trials Design; Cognition; Cognitive; Consensus; Data; Depressed mood; Disease; Disease remission; Excessive Daytime Sleepiness; Functional disorder; Genes; Hour; Human; Impaired cognition; Impairment; Individual; Intervention; Label; Learning; Light; Manic; Measures; Memory; Memory impairment; Mental Depression; Modafinil; Monitor; Moods; Narcolepsy; Nature; Neurocognition; Neurocognitive; Neurologic; Outcome Measure; Outpatients; Paper; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Placebo Control; Placebos; Process; Psychotic Disorders; Publishing; Quality of life; Questionnaires; Randomized; Recovery; Recurrence; Relapse; Relative (related person); Reporting; Risk; Safety; Schedule; Schizophrenia; Short-Term Memory; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Social Interaction; Stabilizing Agents; Symptoms; Testing; Time; United States Food and Drug Administration; Variant; Wakefulness; base; clinically relevant; cognitive function; computerized; depressive symptoms; diaries; executive function; experience; falls; functional disability; improved; novel; novel strategies; offspring; preference; primary outcome; processing speed; psychosocial; psychostimulant; psychotic symptoms; public health relevance; shift work; sleep abnormalities; sleep regulation; social; standard care; theories; trait; week trial

DESCRIPTION (provided by applicant): Despite advances in the treatment of bipolar disorder, most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, many patients continue to experience sleep disturbances, reduced daytime activity levels, and neurocognitive dysfunction. These persistent features of the illness represent critical treatment targets, as they do not adequately improve with standard mood stabilizing medications and they are strongly associated with functional disability and poor quality of life. Psychosocial therapies have focused on the importance of stabilizing sleep-wake cycles and daily routines such as mealtimes and regular social interactions, resulting in significant reductions in affective relapse. No study, to date, has attempted to stabilize circadian rhythms using a pharmacologic intervention in bipolar patients. Thus, the proposed 8-week, randomized, placebo-controlled pilot study will evaluate the safety and preliminarily assess the efficacy of the wake-promoting drug, modafinil (Provigil(R)), on sleep, daytime activity, and neurocognitive functioning in 48 euthymic bipolar patients. Modafinil is approved by the US Food and Drug Administration (FDA) for excessive daytime sleepiness associated with several sleep disorders (narcolepsy, sleep apnea, and shift-work disorder). In an off-label application, we will administer randomize in a 2:1 ratio to active modafinil (200mg/day) or placebo to 48 affectively stable patients with bipolar I disorder for 8 weeks. We will measure patients' subjective experience of sleep disruption and daytime wakefulness by questionnaires and daily diaries. In addition, we will focus on modafinil's potential to improve neurocognitive functioning, including attention, memory and higher order cognitive processes in patients with bipolar disorder, as it has previously been shown to enhance cognition in psychiatrically healthy individuals, patients with sleep disorders, and patients with schizophrenia. To measure cognitive functioning, we will deploy several paper-pencil and computerized tests before modafinil is administered and again at the end of the 8-week study. Finally, although not a primary focus of the current study, we will also investigate the effects of modafinil on low-grade depressive symptoms independent of sleep ratings, regularity of social rhythms, and patient-reported quality of life. We will closely monitor patiets for unforeseen changes in mood symptoms that are deemed to place them at risk for developing mania or depression and will discontinue the trial as deemed necessary. We expect that findings from this study will identify a novel approach for treating those persistent symptoms of bipolar disorder not adequately addressed with current mood stabilizing agents, potentially resulting in a more complete recovery and improvement in day-to-day functioning.

描述（由申请人提供）：尽管治疗了双相情感障碍，但大多数患者仍未实现完全的表演间恢复和功能障碍。在相对缓解期间，许多患者继续遭受睡眠障碍，白天活动水平降低和神经认知功能障碍。这些疾病的持续特征代表了关键的治疗靶标，因为它们无法通过标准的情绪稳定药物得到充分的改善，并且与功能障碍和生活质量差有密切相关。社会心理疗法的重点是稳定睡眠效果周期和日常工作（例如进餐时间和定期社交互动）的重要性，从而大大降低了情感复发。迄今为止，还没有尝试使用两极性患者的药理学干预来稳定昼夜节律。因此，提出的为期8周，随机，安慰剂对照的试点研究将评估促唤醒药物莫达非尼（Provigil（r）），睡眠，白天活动和神经认知功能在48例48例齐射双极性患者中的安全性。 莫达非尼获得美国食品药品监督管理局（FDA）的批准，用于与多种睡眠障碍有关的白天嗜睡过多（睡病，睡眠呼吸暂停和转移工作障碍）。在标签外应用中，我们将以2：1的比例与活动莫达非尼（200mg/天）或安慰剂与48例情感稳定的双相I障碍患者进行随机进行施用，持续8周。我们将通过问卷和日记来衡量患者对睡眠中断和白天清醒的主观经验。此外，我们将重点关注莫达非尼（Modafinil）提高神经认知功能的潜力，包括注意，记忆和躁郁症患者的高阶认知过程，因为它以前已被证明可以增强精神健康患者的认知，睡眠障碍患者和精神分裂症患者的认知。为了衡量认知功能，我们将在对莫达非尼进行几次纸笔和计算机测试进行部署，并在为期8周的研究结束时再次进行莫达非尼。最后，尽管不是当前研究的主要重点，但我们还将研究莫达非尼对与睡眠评级，社交节奏的规律性和患者报告的生活质量无关的低度抑郁症状的影响。 我们将密切监视Patiets的情绪症状的明显变化，这些变化被认为使他们面临躁狂或抑郁症的风险，并将在认为必要的情况下停止试验。我们预计，这项研究的发现将确定一种新的方法来治疗那些与当前情绪稳定剂有关的躁郁症持续症状，这可能导致日常功能的恢复和改善。