Pharmacotherapy and Mechanisms of Sleep Disturbance in Alcohol Dependence (MA)
|ClinicalTrials.gov Identifier: NCT01014533|
Recruitment Status : Completed
First Posted : November 17, 2009
Results First Posted : November 1, 2017
Last Update Posted : December 6, 2017
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:
- To investigate three potential mechanisms of sleep disturbance in alcoholic patients: impaired sleep drive, impaired circadian regulation of alertness, and brain hyperactivation;
- To investigate short-term effects of medication on sleep and its regulatory mechanisms in alcoholics;
- 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.
|Condition or disease||Intervention/treatment|
|Alcohol Dependence Insomnia||Drug: Placebo dispensed to subject. Drug: Gabapentin dispensed to subject.|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||59 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||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.|
|Actual Study Start Date :||May 2007|
|Primary Completion Date :||September 2011|
|Study Completion Date :||September 2011|
Placebo Comparator: 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.
Drug: Placebo dispensed to subject.
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.
Active Comparator: 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.
Drug: Gabapentin dispensed to subject.
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 Name: Neurontin is the brand name for Gabapentin.
- Percentage of Total Sleep Time in Stage 2 Sleep Pre- and Post-study Medication (Stage 2 Percent) [ Time Frame: 1 week ]Electrophysiological measures of sleep stages: percent of total sleep time in stage 2 sleep
- Wake Time After Sleep Onset (WASO) Measured in Sleep Laboratory Recordings Pre- and Post- Study Medication [ Time Frame: 1 week ]Wake time after sleep onset (WASO) (number of minutes awake throughout the night after initial sleep onset)
- Relapse to Any Drinking [ Time Frame: 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01014533
|United States, Michigan|
|University of Michigan Health System|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Kirk J Brower, M.D.||University of Michigan|