Pharmacotherapy and Mechanisms of Sleep Disturbance in Alcohol Dependence
Condition: Alcohol Dependence; Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders; Dyssomnias; Parasomnias; Alcoholism
Study type: Interventional

Summary: 
      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.
    


Intervention name(s): Placebo dispensed to subject.; Gabapentin dispensed to subject.
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Neurontin is the brand name for Gabapentin.
Intervention MeSH terms: Gabapentin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Alcoholism; Alcohol dependence; Insomnia; Dim light melatonin onset; Gabapentin