Pharmacotherapy and Mechanisms of Sleep Disturbance in Alcohol Dependence

NCT01014533 | Completed Results DMC

• 2 other identifiers: HUM000109471R01AA016117-01A1
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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

Conditions

Alcohol Dependence; Insomnia

Keywords

Alcoholism; Alcohol dependence; Insomnia; Dim light melatonin onset; Gabapentin

Outcome Measures

Primary Outcomes (2)

• Percentage of Total Sleep Time in Stage 2 Sleep Pre- and Post-study Medication (Stage 2 Percent)

  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

  Wake time after sleep onset (WASO) (number of minutes awake throughout the night after initial sleep onset)

  1 week

Secondary Outcomes (1)

• Relapse to Any Drinking

  12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Gabapentin

ACTIVE COMPARATOR

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.

Interventions

Placebo dispensed to subject. DRUG

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.

Placebo

Gabapentin dispensed to subject. DRUG

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.

Also known as: Neurontin is the brand name for Gabapentin.

Gabapentin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dr. Kirk Brower: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Alcoholism; Sleep Initiation and Maintenance Disorders

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Kirk Brower
• Organization: University of Michigan

kbrower@med.umich.edu

Study Officials

• Kirk J Brower, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: November 17, 2009
• Study Start: May 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: December 6, 2017
• Results First Posted: November 1, 2017

Record last verified: 2017-10

Locations

US (1)