The Effects of Quetiapine (Seroquel XR) on Sleep During Alcohol Abstinence

• Sponsor: Subhajit Chakravorty (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00434876
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism; Sleep Initiation and Maintenance Disorders	Drug: Quetiapine XR; Drug: Placebo.	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effects of Quetiapine on Sleep During Alcohol Abstinence
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Quetiapine XR	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.; Other Names: Seroquel XR
Placebo Comparator: 2 Placebo	Drug: Placebo.; Inactive or inert pill which will be used as a comparator.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Philadelphia, OPC	Philadelphia	Pennsylvania	United States	19106

Sponsors and Collaborators

• Subhajit Chakravorty

Investigators

• Principal Investigator: Subhajit Chakravorty, MD, Philadelphia, OPC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Subhajit Chakravorty, Staff Physician, Corporal Michael J. Crescenz VA Medical Center
• ClinicalTrials.gov Identifier: NCT00434876
• Other Study ID Numbers: 101206
• First Posted: Feb 14, 2007
• Last Update Posted: Aug 9, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Subhajit Chakravorty, Staff Physician, Corporal Michael J. Crescenz VA Medical Center: Alcoholism; Insomnia; Quetiapine; Seroquel
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Alcoholism; Alcohol Abstinence; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	Addiction psychiatry clinic, behavioral health laboratory, and self referrals solicited through flyers.

Arm/Group Title	Quetiapine XR	Placebo
Arm/Group Description	The pills were taken at bedtime and the dose was titrated flexibly in the following fashion over the first week: 50 mg dose for 2 nights, followed by 200 mg a night for 2 nights, and then 300 mg a night for 2 nights and to a final dose of 400 mg daily starting on night # 7. Medication taper commenced at week 8 in the reverse stepwise fashion after the second set of two polysomnograms.	The matching placebo pills were similarly taken at bedtime and the dose was titrated flexibly in the following fashion over the first week: 50 mg dose for 2 nights, followed by 200 mg a night for 2 nights, and then 300 mg a night for 2 nights and to a final dose of 400 mg daily starting on night # 7. Medication taper commenced at week 8 in the reverse stepwise fashion after the second set of two polysomnograms.
Period Title: Overall Study
STARTED	11	11
COMPLETED	10	10
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Quetiapine	Placebo	Total
Arm/Group Description	Quetiapine XR	Placebo	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (6)	51 (8)	52 (7)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	10 100%	10 100%	20 100%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Sleep Efficiency (From an In-laboratory Polysomnogram)
Description	The fraction of time spent asleep to the total time in bed (%).
Time Frame	Baseline, and week 8 of treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine XR	Placebo
Arm/Group Description	Quetiapine XR	Placebo
Measure Participants	10	10
Sleep Efficiency (baseline)	70.70 (17.49)	78.63 (12.89)
Sleep Efficiency (after 8 weeks of treatment)	79.45 (16.52)	82.80 (11.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Quetiapine XR, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Insomnia Severity Index (ISI)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine XR	Placebo
Arm/Group Description	Quetiapine XR	Placebo
Measure Participants	10	10
ISI (baseline)	17.00 (4.08)	14.80 (7.14)
ISI (week 7)	5.40 (4.83)	6.70 (7.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Quetiapine XR, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Pittsburgh Sleep Quality Index (PSQI)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine XR	Placebo
Arm/Group Description	Quetiapine XR	Placebo
Measure Participants	10	10
PSQI (baseline)	14.70 (1.94)	14.60 (1.71)
PSQI (week 4)	13.20 (2.61)	13.80 (2.04)
PSQI (week 9)	14.50 (2.56)	13.80 (2.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Quetiapine XR, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Wake After Sleep Onset Time (WASO) From an In-laboratory Polysomnogram.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine XR	Placebo
Arm/Group Description	Quetiapine XR	Placebo
Measure Participants	10	10
WASO (baseline)	101.87 (81.80)	61.17 (37.77)
WASO (week 8)	60.71 (71.41)	66.99 (60.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Quetiapine XR, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Arm/Group Title	Quetiapine		Placebo
Arm/Group Description	Quetiapine XR		Placebo
All Cause Mortality
	Quetiapine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Quetiapine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		2/10 (20%)
Psychiatric disorders
Suicidal ideation	1/10 (10%)	1	1/10 (10%)	1
Relapse to heavy alcohol use leading to inpatient admission	1/10 (10%)	1	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Quetiapine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		3/10 (30%)
Cardiac disorders
Dizziness	1/10 (10%)		1/10 (10%)
Gastrointestinal disorders
Dry mouth	2/10 (20%)		0/10 (0%)
Constipation	1/10 (10%)		0/10 (0%)
General disorders
Fatigue	2/10 (20%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Somatic pain	1/10 (10%)		0/10 (0%)
Nervous system disorders
Headache	0/10 (0%)		1/10 (10%)
Psychiatric disorders
Somnolence	7/10 (70%)		3/10 (30%)
Insomnia	2/10 (20%)		0/10 (0%)
Increased apetite	1/10 (10%)		0/10 (0%)
Agitation	1/10 (10%)		0/10 (0%)
Decreased motivation	0/10 (0%)		1/10 (10%)

Limitations/Caveats

The limitations of this study include the small sample size, and assessment of PSQI, PHQ-9, BAI, and SF-12 at week 9 (immediately after washout from the study drug). The corruption of stored online actigraphic sleep data prevented its interpretation.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.