Official Title: “The Effects of Quetiapine on Sleep During Alcohol Abstinence”

The purpose of this study to determine how effective quetiapine (seroquel XR) is in improving the sleep and also maintaining sobriety in recovering alcohol dependent veteran subjects.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2008

Sober alcoholics frequently complain of difficulty falling asleep as well as staying asleep which may eventually lead to relapse. Previous research reports a relationship between sleep problems and alcoholism, with ten percent of all alcoholism-related costs attributable to insomnia and its consequences. Novel antipsychotic medications such as quetiapine have been investigated for efficacy in treating alcoholism. A recent pilot study of quetiapine, conducted at the affiliated University of Pennsylvania Medical Center, demonstrated its efficacy in promoting sleep and reducing alcohol use among alcohol dependent subjects.

The primary aim of this study is to determine the degree to which quetiapine improves insomnia in veterans during the early phase of recovery from alcohol dependence. The sleep efficiency (from an in-lab polysomnogram) will be the primary outcome measure, to assess the overall improvement in sleep. Secondary measures of sleep will include the objective sleep-wake recordings using actigraphy, Pittsburgh Sleep Quality Index, Insomnia Severity Index (to assess insomnia characteristics), Epworth Sleepiness Scale (to assess daytime sleepiness). A secondary aim is to assess the relationship between insomnia severity and alcohol use. The Time Line Follow Back measure will be the outcome measure to assess alcohol use between visits. Another additional aim will be to assess the relationship between change in the anxiety and depressive symptoms and an improvement in the sleep on the quetiapine. The PHQ-9, Hamilton Anxiety Rating Scale, Timeline Follow Back measure, sleep efficiency (from an in-laboratory polysomnogram), the objective sleep-wake recordings using the actigraph and the Pittsburgh Sleep Quality Index,will be used as the outcome measures.

To meet the aims of this study, 24 subjects will be enrolled. After achieving at least 3 days of abstinence, participants will be undergo baseline screening for psychiatric, medical and sleep disorders as well as drug use disorders, including a portable home sleep study.

Subsequently the subjects will stay for two consecutive nights in sleep laboratory. After the first set of sleep studies, subjects will be randomly assigned to receive either placebo or quetiapine. The subjects will then be followed weekly using the Medical Management paradigm (similar to the one used in the NIAAA COMBINE study). Medical Management is a standardized psychosocial intervention which is medically based and focused on alcohol abstinence and medication compliance and conducted by a qualified nurse or the principal investigator. This intervention will initially include feedback to the subject, psycho-education about his/her alcohol use disorder and currently prescribed study medication. The dose of quetiapine XR will gradually be increased up to a target dose of 400mg/ day over 7 days, maintained as such for seven weeks. This will be followed by a second two night polysomnography study. After the overnight sleep studies the quetiapine will be tapered off, over the next 7 days.

Intervention(s) in this Clinical Trial

• Drug: Quetiapine XR
  • Quetiapine is a second generation antipsychotic medication, which has also recently shown to be associated with properties of mood stabilization in bipolar disorder.
• Drug: Placebo.
  • Inactive or inert pill which will be used as a comparator.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Quetiapine XR
• Placebo Comparator: 2
  • Placebo

Primary Measures

• Sleep Efficiency (from an in-laboratory polysomnogram)
  • Time Frame: 8 weeks.
    Safety Issue?: No

Secondary Measures

• Objective sleep-wake recordings using actigraphy.
  • Time Frame: 8 weeks.
    Safety Issue?: No
• Pittsburgh Sleep Quality Index, Insomnia Severity Index and Epworth Sleepiness Scale.
  • Time Frame: 8 weeks.
    Safety Issue?: No
• Time Line Followback, Penn Alcohol craving scale.
  • Time Frame: 8 weeks.
    Safety Issue?: No
• PHQ-9, Beck's Anxiety Rating Scale
  • Time Frame: 8 weeks.
    Safety Issue?: No

Inclusion Criteria:

• Males and females between the ages of 18-65 years DSM-IV diagnosis of current alcohol dependence Drinking criteria: drinks more than an average of 12 standard drinks/week in the last 30 drinking days.
• Can speak, understand, and print in English Is capable of giving written informed consent

Exclusion Criteria:

• Positive urine drug screen for opioids, cocaine, or amphetamine (excluding THC) Subject has abused or been dependent on opiates or other psychoactive substances (excluding alcohol, nicotine or occasional use of marijuana) in the past 12 months. Use of prescription opioids prior to treatment entry is allowed at discretion of the PI Hepatocellular disease
• [as indicated by serum ALT/AST (ALT/AST > 4)] at baseline.
• Any current unstable or serious psychiatric condition (e.g. schizophrenia, bipolar disorder, or PTSD) Any unstable or serious medical/neurologic illness including cataracts
• [posterior capsular/ nuclear (grade NS3 or more)] or epilepsy Regular use of any psychotropic medications/ disulfiram regularly within the last 7 days prior to randomization or needs immediate treatment with a psychotropic medication (except for detoxification medications or benadryl used sparingly for sleep) Subjects who are pregnant, nursing, or not using a reliable method of contraception History of hypersensitivity to antipsychotic drugs, including quetiapine Evidence of severe cognitive impairment Patient with severe sleep apnea (sleep study with an apnea-hypopnea index > 30) on the first night of baseline polysomnograms

Patient with diabetes mellitus meeting one or more of the following criteria:

• Unstable DM, defined as enrollment glycosylated hemoglobin (HbA1c) > 8.5%
• Unstable DM as evidenced by a change in insulin dose of > 10% or recent (< 8 weeks) change in oral hypoglycemic dose

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Department of Veterans Affairs

Overall Clinical Trial Officials and Contacts

Subhajit Chakravorty, MD Principal Investigator Philadelphia, OPC  

Overall Contact: Lauren Witte, BA (215) 823-5800 Lauren.Witte@va.gov

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00434876

Study ID Number: 101206

ClinicalTrials.gov Identifier: NCT00434876

Health Authority: United States: Federal Government