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Pharmacotherapy and Mechanisms of Sleep Disturbance in Alcohol Dependence (MA)

2017年10月31日 更新者:Dr. Kirk Brower

This is a Study Exploring the Reasons Why People With Alcohol Dependence Have Sleep Disturbances, and Whether or Not a Study Medication, Gabapentin, vs. Placebo, Affects Those Sleep Patterns.

Insomnia and other sleep abnormalities are common, persistent, and associated with relapse in alcohol-dependent patients. The overall, long-term objectives of the proposed research are to investigate the neurophysiologic mechanisms of sleep disturbance that are associated with relapse in patients with alcohol dependence, and to target those mechanisms with medication in order to reduce relapse risk.

The specific research aims are:

  1. To investigate three potential mechanisms of sleep disturbance in alcoholic patients: impaired sleep drive, impaired circadian regulation of alertness, and brain hyperactivation;
  2. To investigate short-term effects of medication on sleep and its regulatory mechanisms in alcoholics;
  3. To investigate the short-term clinical course of alcoholism as a function of baseline sleep parameters.

In Study Phases I & II (Screening & Baseline: 10+ days), subjects are assessed to diagnose alcohol dependence, determine baseline values for drinking and sleeping, and rule out confounding sleep-impairing causes.

Phase III (Medication: 10 days), is a randomized, double-blind parallel design comparison of gabapentin vs. placebo on mechanisms of sleep. It is not a therapeutic or clinical trial. Phases II & III each have 7 days of monitoring sleep and activity, followed by 3 nights in the University of Michigan (UM) sleep laboratory to assess all-night EEG activity and Dim-Light Melatonin Onset (DLMO), a measure of circadian rhythm.

Phase IV is a 2-day medication taper and Phase V (Follow-up) consists of one visit or telephone call after 12 weeks to assess course of drinking.

In summary, sleep disturbance in alcoholic patients increases their risk of relapse. This study proposes to investigate the mechanisms causing sleep disturbance in alcoholics and to determine if those mechanisms predict return to drinking after 12 weeks.

Relevance: Alcoholism is a devastating chronic disorder that in any one year affects 10% of adults, costs over $185 billion, and causes more than 100,000 deaths in the U.S. Despite treatment, most alcoholic patients achieve only short-term abstinence. Medically-based treatment improvements are needed that target neurophysiologic mechanisms of relapse. Overall public health will be improved by developing science-based treatments that can augment existing, but only partially effective, treatment approaches.

研究概览

研究类型

介入性

注册 (实际的)

59

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Michigan
      • Ann Arbor、Michigan、美国、48109
        • University of Michigan Health System

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 65年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Meet DSM-IV criteria for alcohol dependence (as confirmed by the SCID)
  • Between 3 and 12 weeks since last drink (as measured by the TLFB)
  • At least 2 weeks since last detoxification medication, if relevant
  • An alcohol withdrawal rating score < 8 (as measured by the CIWA-Ar) to rule out acute alcohol withdrawal effects on sleep.
  • Expresses a desire to stop drinking or a willingness to abstain from alcohol and/or other drugs of abuse (except nicotine) during the course of the study

Exclusion Criteria:

  • Subjects who meet DSM-IV criteria for dependence on any psychoactive substance other than alcohol (except nicotine) in the past 3 months (per SCID interview).
  • Subjects with a current (past 1 month) DSM-IV diagnosis of panic disorder, generalized anxiety disorder, post-traumatic stress disorder, major depression, anorexia nervosa, or bulimia nervosa (per SCID interview) and/or that require ongoing psychotropic medication.
  • Subjects who have a lifetime diagnosis meeting DSM-IV criteria for bipolar disorder, schizophrenia, schizoaffective disorder, delusional (paranoid) disorders, or obsessive-compulsive disorder.
  • Urine drug screen positive for amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, or opioids. (If positive, subjects have one opportunity to test negative after a week of abstinence).
  • Medical disorders or pain syndromes that may affect sleep; history of head trauma with loss of consciousness; history of seizures (except alcohol-related seizures).
  • Subjects with elevated renal tests (blood urea nitrogen or creatinine), because gabapentin is renally eliminated, or elevated liver transaminases (>3X normal), or abnormal thyroid tests as thyroid problems can affect sleep.
  • Sleep disorders other than insomnia such as sleep apnea/hypopnea index >10 per hour or periodic limb movement disorder; PLM>15 movements per hour with arousals.
  • Taking medications known to affect sleep (e.g., antidepressants, anticonvulsants, centrally acting antihistamines, neuroleptics, sedative-hypnotics, stimulants, centrally acting antihypertensives [alpha-methyldopa, reserpine, clonidine], oral corticosteroids, and theophylline within the past 2 weeks or 5 weeks for fluoxetine).
  • Subjects taking medications used to treat addiction (e.g., disulfiram, naltrexone or acamprosate) are excluded because of unknown effects on sleep.
  • Subjects who do evening or midnight shift work. (Subjects who have traveled across multiple time zones in the previous two weeks will be included only at the discretion of the P.I.)
  • Pregnancy, breast feeding, or inadequate contraception in women of child-bearing potential.
  • Subjects who are unable or unlikely to follow the study protocol in the investigator 's opinion, because of cognitive deficits (Mini-Mental State Exam score < 27), a personality disorder, a serious suicide risk, dangerousness to others, illiteracy, or unstable or distant living situation.
  • Subjects with a known allergy, hypersensitivity or contraindication to study medication.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:其他
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:双倍的

武器和干预

参与者组/臂
干预/治疗
安慰剂比较:Placebo
After 3 nights in the UM sleep lab and randomization, this arm receives placebo for one week. They then return to the sleep lab for the same procedures.
Placebo for 11 days, (one pill at bedtime on nights 1 and 2, 2 pills at bedtime on nights 3-10, and 1 pill at bedtime on night 11, then D/C). They return to the Sleep Lab for polysomnography on nights 8 - 10 of medication so their sleep data can be compared.
有源比较器:Gabapentin
After spending 3 baseline nights in the UM sleep lab, alcohol dependent subjects are randomized. This arm receives gabapentin . On nights 1 and 2 of medication, the dose is 600 mg by mouth 30 min before bedtime. On nights 3-10, the dose is 1200 mg by mouth 30 min before bedtime. On nights 8-10 of medication, subjects return to the UM sleep lab and complete 3 sleep nights with the same procedures. On night 11, the dose is reduced to 600 mg by mouth 30 min before bedtime, and then stopped.
After spending 3 baseline nights in the UM Sleep Lab, alcohol dependent subjects are randomized to receive either gabapentin or placebo for 11 days. (1 pill (600 mg) at bedtime on nights 1 and 2, 2 pills (totalling 1200 mg) at bedtime on nights 3-10, and 1 pill (600 mg) at bedtime on night 11, then D/C). On nights 8 - 10 of medication, subjects return to the lab and sleep 3 more nights with the same procedures.
其他名称:
  • Neurontin is the brand name for Gabapentin.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Percentage of Total Sleep Time in Stage 2 Sleep Pre- and Post-study Medication (Stage 2 Percent)
大体时间:1 week
Electrophysiological measures of sleep stages: percent of total sleep time in stage 2 sleep
1 week
Wake Time After Sleep Onset (WASO) Measured in Sleep Laboratory Recordings Pre- and Post- Study Medication
大体时间:1 week
Wake time after sleep onset (WASO) (number of minutes awake throughout the night after initial sleep onset)
1 week

次要结果测量

结果测量
措施说明
大体时间
Relapse to Any Drinking
大体时间:12 weeks
Relapse to any drinking is counted as participants who drank any beverage alcohol from end of sleep laboratory study (night 10) to twelve weeks later
12 weeks

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Kirk J Brower, M.D.、University of Michigan

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2007年5月1日

初级完成 (实际的)

2011年9月1日

研究完成 (实际的)

2011年9月1日

研究注册日期

首次提交

2009年11月16日

首先提交符合 QC 标准的

2009年11月16日

首次发布 (估计)

2009年11月17日

研究记录更新

最后更新发布 (实际的)

2017年12月6日

上次提交的符合 QC 标准的更新

2017年10月31日

最后验证

2017年10月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

Placebo dispensed to subject.的临床试验

3
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