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

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Dr. Kirk Brower, University of Michigan
ClinicalTrials.gov Identifier:
NCT01014533
First received: November 16, 2009
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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 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 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 Intervention
Alcohol Dependence
Insomnia
Drug: Gabapentin or placebo dispensed to subject.

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Sleep architecture (quality of sleep) [ Time Frame: 1 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse to heavy drinking [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: May 2007
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Alcohol dependent subjects spend 3 nights in the UM sleep lab, then are randomized to receive either gabapentin or placebo for one week. They then return to the sleep lab for the same procedures. Healthy control subjects don not participate in the medication arm of the study.
Drug: Gabapentin or placebo dispensed to subject.
Alcohol dependent subjects have polysomnography in the UM Sleep Lab for three nights, then are randomized to receive gabapentin or placebo for 11 days, (600mg at bedtime on night 1, 1200mg at bedtime on nights 2-10, and 600mg at bedtime on night 11, then D/C). They return to the Sleep Lab for polysomnography on night 8 of medication so their sleep data can be compared.
Other Name: Neurontin
Drug: Gabapentin or placebo 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. On the 8th night of medication, subjects return to the lab and sleep 3 more nights with the same procedures. Control subjects don't participate in the medication arm of the study; they just complete the first 3 baseline sleep nights.
Other Name: Neurontin is the brand name for Gabapentin.
Active Comparator: Gabapentin
Alcohol dependent subjects are randomized to receive gabapentin or placebo after spending 3 baseline nights in the UM sleep lab. On Night 8 of medication, subjects return to the UM sleep lab and complete 3 sleep nights with the same procedures.
Drug: Gabapentin or placebo dispensed to subject.
Alcohol dependent subjects have polysomnography in the UM Sleep Lab for three nights, then are randomized to receive gabapentin or placebo for 11 days, (600mg at bedtime on night 1, 1200mg at bedtime on nights 2-10, and 600mg at bedtime on night 11, then D/C). They return to the Sleep Lab for polysomnography on night 8 of medication so their sleep data can be compared.
Other Name: Neurontin
Drug: Gabapentin or placebo 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. On the 8th night of medication, subjects return to the lab and sleep 3 more nights with the same procedures. Control subjects don't participate in the medication arm of the study; they just complete the first 3 baseline sleep nights.
Other Name: Neurontin is the brand name for Gabapentin.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)

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.
  • On 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 on 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01014533

Locations
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Dr. Kirk Brower
Investigators
Principal Investigator: Kirk J Brower, M.D. University of Michigan
  More Information

No publications provided

Responsible Party: Dr. Kirk Brower, Professor of Psychiatry, University of Michigan
ClinicalTrials.gov Identifier: NCT01014533     History of Changes
Other Study ID Numbers: HUM00010947, 1R01AA016117-01A1
Study First Received: November 16, 2009
Last Updated: January 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
Alcoholism
Alcohol dependence
Insomnia
Dim light melatonin onset
Gabapentin

Additional relevant MeSH terms:
Alcoholism
Dyssomnias
Sleep Disorders
Parasomnias
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Ethanol
Gabapentin
Gamma-Aminobutyric Acid
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anticonvulsants
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014