Alcoholism, Sleep Initiation and Maintenance Disorders
Conditions
Keywords
Alcoholism, Insomnia, Quetiapine, Seroquel
Brief summary
The primary purpose of this study is to determine how efficacy of quetiapine (seroquel XR) in improving the sleep in recovering alcohol dependent subjects.
Detailed description
Sober alcohol dependent subjects frequently complain of difficulty falling asleep as well as staying asleep which may eventually lead to relapse. Novel antipsychotic medications such as quetiapine have shown some efficacy in treating alcoholism and have also shown some benefit in improving insomnia. The primary aim of this study is to determine the degree to which quetiapine improves sleep 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. Secondary measures of sleep will include the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and actigraphy. Other additional aims will explore for alcohol use and cravings, change in psychiatric symptoms using the The Time Line Follow Back measure, Penn Alcohol Craving Scale (PACS), the Patient Health Questionnaire-9 item scale (PHQ-9), and the Beck's Anxiety Inventory (BAI) respectively. Twenty four subjects within the first year of sobriety will be enrolled. Participants will be undergo an extensive baseline screening procedure. After 2 consecutive in-laboratory polysomnograms they will be treated with either Quetiapine XR or matching placebo pills targetting a dose of 400 mg a night. The treatment duration will be 8 weeks and during the eight week of treatment they will undergo 2 more nights of in-laboratory polysomnogram. All subjects will also receive Medical Management therapy, a standardized psychosocial intervention which is medically-based and focusses on alcohol abstinence and medication compliance.
Interventions
DRUGQuetiapine XR
Quetiapine is a second generation antipsychotic medication, which has also recently shown to be associated with properties of mood stabilization in bipolar disorder.
DRUGPlacebo.
Inactive or inert pill which will be used as a comparator.
Sponsors
Subhajit Chakravorty
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
subjects between the ages of 18-65 years, with a DSM-IV diagnosis of current alcohol dependence (past year), can speak, understand, and print in English, and is capable of giving written informed consent
Exclusion criteria
Positive urine drug screen for opioids, cocaine, or amphetamine (excluding THC), dependence on other drugs excluding alcohol/nicotine/cannabis over the past year, unstable psychiatric, medical disorders, cataracts \[posterior capsular/ nuclear (grade NS3 or more), currently on any maintenance psychotropic medications affecting sleep, currently pregnant, nursing, or not using a reliable method of contraception; history of hypersensitivity to antipsychotic drugs, including quetiapine, severe cognitive impairment, severe untreated obstructive sleep apnea, and inadequately controlled diabetes mellitus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Efficiency (From an In-laboratory Polysomnogram) | Baseline, and week 8 of treatment. | The fraction of time spent asleep to the total time in bed (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insomnia Severity Index (ISI) | Baseline, weeks 1, 3, 5, and 7 of treatment. | ISI total score; this scale assesses for global insomnia severity (range 0-24). Higher scale scores indicate higher insomnia severity. |
| Pittsburgh Sleep Quality Index (PSQI) | Baseline, weeks 4, and 9. | PSQI total score (range 0-21). A PSQI total score \> 5 indicates insomnia, with higher scores denoting a decrease in sleep quality. The PSQI global score assesses for the overall quality of sleep and is computed by adding the 7 component scale scores. This widely used 19-item self-rated scale evaluates the subjective quality of sleep over the last 4 weeks. The PSQI was administered at baseline, and weeks 4, and 9. |
| Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram. | Baseline, and week 8 | The amount of time spent awake after initially falling asleep and before final awakening (in minutes). None to a fewer minutes is better (than a higher number of minutes). |
Countries
United States
Participant flow
Recruitment details
Addiction psychiatry clinic, behavioral health laboratory, and self referrals solicited through flyers.
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine Quetiapine XR | 10 |
| Placebo Placebo | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Quetiapine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age Continuous | 51 years STANDARD_DEVIATION 8 | 53 years STANDARD_DEVIATION 6 | 52 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 10 | 3 / 10 |
| serious Total, serious adverse events | 2 / 10 | 2 / 10 |
Outcome results
Primary
Sleep Efficiency (From an In-laboratory Polysomnogram)
The fraction of time spent asleep to the total time in bed (%).
Time frame: Baseline, and week 8 of treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine XR | Sleep Efficiency (From an In-laboratory Polysomnogram) | Sleep Efficiency (baseline) | 70.70 percentage | Standard Deviation 17.49 |
| Quetiapine XR | Sleep Efficiency (From an In-laboratory Polysomnogram) | Sleep Efficiency (after 8 weeks of treatment) | 79.45 percentage | Standard Deviation 16.52 |
| Placebo | Sleep Efficiency (From an In-laboratory Polysomnogram) | Sleep Efficiency (baseline) | 78.63 percentage | Standard Deviation 12.89 |
| Placebo | Sleep Efficiency (From an In-laboratory Polysomnogram) | Sleep Efficiency (after 8 weeks of treatment) | 82.80 percentage | Standard Deviation 11.57 |
p-value: 0.49Mixed Models Analysis
Secondary
Insomnia Severity Index (ISI)
ISI total score; this scale assesses for global insomnia severity (range 0-24). Higher scale scores indicate higher insomnia severity.
Time frame: Baseline, weeks 1, 3, 5, and 7 of treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine XR | Insomnia Severity Index (ISI) | ISI (baseline) | 17.00 units on a scale | Standard Deviation 4.08 |
| Quetiapine XR | Insomnia Severity Index (ISI) | ISI (week 7) | 5.40 units on a scale | Standard Deviation 4.83 |
| Placebo | Insomnia Severity Index (ISI) | ISI (baseline) | 14.80 units on a scale | Standard Deviation 7.14 |
| Placebo | Insomnia Severity Index (ISI) | ISI (week 7) | 6.70 units on a scale | Standard Deviation 7.34 |
p-value: 0.04Mixed Models Analysis
Secondary
Pittsburgh Sleep Quality Index (PSQI)
PSQI total score (range 0-21). A PSQI total score \> 5 indicates insomnia, with higher scores denoting a decrease in sleep quality. The PSQI global score assesses for the overall quality of sleep and is computed by adding the 7 component scale scores. This widely used 19-item self-rated scale evaluates the subjective quality of sleep over the last 4 weeks. The PSQI was administered at baseline, and weeks 4, and 9.
Time frame: Baseline, weeks 4, and 9.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine XR | Pittsburgh Sleep Quality Index (PSQI) | PSQI (baseline) | 14.70 units on a scale | Standard Deviation 1.94 |
| Quetiapine XR | Pittsburgh Sleep Quality Index (PSQI) | PSQI (week 4) | 13.20 units on a scale | Standard Deviation 2.61 |
| Quetiapine XR | Pittsburgh Sleep Quality Index (PSQI) | PSQI (week 9) | 14.50 units on a scale | Standard Deviation 2.56 |
| Placebo | Pittsburgh Sleep Quality Index (PSQI) | PSQI (baseline) | 14.60 units on a scale | Standard Deviation 1.71 |
| Placebo | Pittsburgh Sleep Quality Index (PSQI) | PSQI (week 4) | 13.80 units on a scale | Standard Deviation 2.04 |
| Placebo | Pittsburgh Sleep Quality Index (PSQI) | PSQI (week 9) | 13.80 units on a scale | Standard Deviation 2.78 |
p-value: 0.57Mixed Models Analysis
Secondary
Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram.
The amount of time spent awake after initially falling asleep and before final awakening (in minutes). None to a fewer minutes is better (than a higher number of minutes).
Time frame: Baseline, and week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine XR | Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram. | WASO (baseline) | 101.87 minutes | Standard Deviation 81.8 |
| Quetiapine XR | Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram. | WASO (week 8) | 60.71 minutes | Standard Deviation 71.41 |
| Placebo | Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram. | WASO (baseline) | 61.17 minutes | Standard Deviation 37.77 |
| Placebo | Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram. | WASO (week 8) | 66.99 minutes | Standard Deviation 60.62 |
p-value: 0.03Mixed Models Analysis