Effects of Eszopiclone on Sleep and Memory in Schizophrenia

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01641900
• Collaborator: Beth Israel Deaconess Medical Center (Other), Mclean Hospital (Other)
• Enrollment: 59
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The investigators will test the hypothesis that the sleep medication, eszopiclone, can normalize brain activity during sleep and improve memory in patients with schizophrenia. The investigators will do this by measuring sleep and memory performance on two conditions separated by one week: taking 3 mg of eszopiclone and taking placebo. The investigators will study healthy subjects and chronic, medicated outpatients with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: eszopiclone; Drug: placebo	N/A

Detailed Description

Sleep spindles, a defining oscillation of stage 2 non-rapid eye movement sleep (N2), are strongly linked to memory and IQ in healthy individuals. Schizophrenia is characterized by a spindle deficit that correlates with deficient sleep-dependent memory consolidation, symptom severity, IQ and executive function. In a small pilot study of schizophrenia patients, eszopiclone , significantly increased sleep spindles but its effect on memory was not significant. Here, in a larger double-blind, placebo-controlled, cross-over design study, we investigated whether eszopiclone can both increase spindle density and improve memory consolidation. Chronic, medicated schizophrenia outpatients and demographically-matched healthy control participants were randomly assigned to receive either placebo first or 3mg of eszopiclone first for two consecutive nights with high density polysomnography. Placebo and eszopiclone visits were one week apart. Participants were trained on the Motor Sequence Task (MST) at bedtime of the second night of each visit and tested the following morning to probe sleep-dependent motor memory consolidation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Sleep-dependent Memory Processing in Schizophrenia
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Schizophrenia Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. All participants receive two interventions: 3 mg eszopiclone and Placebo Intervention conditions are separated by 1 week.	Drug: eszopiclone; 3 mg of eszopiclone for two consecutive nights (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.; Other Names: Lunesta ; Drug: placebo; placebo capsule for two consecutive nights. (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.
Experimental: Healthy Controls Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use. All participants receive two interventions: 3 mg eszopiclone and Placebo Intervention conditions are separated by 1 week.	Drug: eszopiclone; 3 mg of eszopiclone for two consecutive nights (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.; Other Names: Lunesta ; Drug: placebo; placebo capsule for two consecutive nights. (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.

Outcome Measures

Primary Outcome Measures

1. Sleep Spindle Density [Spindles will be averaged for the Baseline (Night 1) and Experimental Nights (Night 2)]

   This measure is averaged for Baseline and Experimental nights. Sleep spindle density (number/minute) for non-Rapid Eye Movement Stage 2 sleep (N2) detected at channel Cz based on polysomnographic recordings.

Secondary Outcome Measures

1. Motor Procedural Memory Performance [Experimental Night (Night 2)]

   Overnight performance improvement on the finger tapping motor sequence task (MST).The MST involves pressing four numerically labeled keys on a standard keyboard with the fingers of the left hand, repeating a 5 digit sequence as quickly and accurately as possible for 12 trials at 30 seconds each separated by 30 sec rest periods. Different sequences were employed for the Placebo and Drug visits in a counter-balanced order. MST performance is measured as the number of correctly typed sequences in each trial. The primary outcome measure is overnight improvement calculated as the percent increase in average of correct sequences from the last three training trials to the average of first three test trials. Since the outcome measure is calculated as percent improvement from training to test for each participant, there is no highest or lowest possible score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• clinically stable outpatients with schizophrenia,

• proficient in English,

• able to give informed consent,

• maintained on a stable dose of atypical antipsychotic medications for at least 6 weeks prior to enrollment.

• healthy Control participants matched as a group to the patients for age, sex, and parental socioeconomic status.

Exclusion Criteria:

• Substance abuse or dependence within the past six months;

• other chronic medical conditions that affect sleep; (- pregnancy/breast feeding;

• hepatic impairment;

• treatment with inhibitors or inducers of CYP 3A4 or 2E1 enzymes (which metabolize eszopiclone);

• a history of head injury resulting in prolonged loss of consciousness or other neurological sequelae; (- mental retardation; (- a diagnosed sleep disorder other than insomnia,

• neurological disorder; sleep disorder, other than insomnia, identified in a clinical sleep evaluation.

Patients on conventional agents, benzodiazepines, or other sleep agents will be excluded. Potential controls will be excluded for a personal history of mental illness, a family history of schizophrenia spectrum disorder or psychosis, and treatment with medications known to affect sleep or cognition.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Beth Israel Deaconess Medical Center
• Mclean Hospital

Investigators

• Principal Investigator: Dara S Manoach, Ph.D., Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dara S. Manoach, PhD, Professor of Psychology, Dept. of Psychiatry, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01641900
• Other Study ID Numbers: R01MH092638
• First Posted: Jul 17, 2012
• Last Update Posted: Jun 14, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Dara S. Manoach, PhD, Professor of Psychology, Dept. of Psychiatry, Massachusetts General Hospital: sleep; memory; schizophrenia; eszopiclone
• Additional relevant MeSH terms: Schizophrenia; Eszopiclone

Study Results

Participant Flow

Arm/Group Title	Group: Schizophrenia	Group: Healthy Controls
Arm/Group Description	Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants completed both the Drug and Placebo arms.	Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use. Participants completed both the Drug and Placebo arms.
Period Title: Overall Study
STARTED	28	31
Completed Placebo Intervention	27	29
Completed Drug Intervention	26	29
COMPLETED	26	29
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Group: Schizophrenia	Group: Healthy Controls	Total
Arm/Group Description	Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants completed both the Drug and Placebo arms.	Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use. Participants completed both the Drug and Placebo arms.	Total of all reporting groups
Overall Participants	26	29	55
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 100%	29 100%	55 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.3 (7.5)	30.1 (6.2)	31.13 (6.91)
Sex: Female, Male (Count of Participants)
Female	5 19.2%	8 27.6%	13 23.6%
Male	21 80.8%	21 72.4%	42 76.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.8%	3 10.3%	4 7.3%
Not Hispanic or Latino	19 73.1%	19 65.5%	38 69.1%
Unknown or Not Reported	6 23.1%	7 24.1%	13 23.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 11.5%	3 10.3%	6 10.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 23.1%	0 0%	6 10.9%
White	12 46.2%	17 58.6%	29 52.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 19.2%	9 31%	14 25.5%
Region of Enrollment (participants) [Number]
United States	26 100%	29 100%	55 100%

Outcome Measures

1. Primary Outcome

Title	Sleep Spindle Density
Description	This measure is averaged for Baseline and Experimental nights. Sleep spindle density (number/minute) for non-Rapid Eye Movement Stage 2 sleep (N2) detected at channel Cz based on polysomnographic recordings.
Time Frame	Spindles will be averaged for the Baseline (Night 1) and Experimental Nights (Night 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group: Schizophrenia	Group: Healthy Controls
Arm/Group Description	Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants completed both the Drug and Placebo arms.	Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use. Participants completed both the Drug and Placebo arms.
Measure Participants	26	29
Placebo (placebo capsule)	2.02 (0.44)	2.13 (0.51)
Drug (3mg eszopiclone)	2.25 (0.41)	2.44 (0.44)

2. Secondary Outcome

Title	Motor Procedural Memory Performance
Description	Overnight performance improvement on the finger tapping motor sequence task (MST).The MST involves pressing four numerically labeled keys on a standard keyboard with the fingers of the left hand, repeating a 5 digit sequence as quickly and accurately as possible for 12 trials at 30 seconds each separated by 30 sec rest periods. Different sequences were employed for the Placebo and Drug visits in a counter-balanced order. MST performance is measured as the number of correctly typed sequences in each trial. The primary outcome measure is overnight improvement calculated as the percent increase in average of correct sequences from the last three training trials to the average of first three test trials. Since the outcome measure is calculated as percent improvement from training to test for each participant, there is no highest or lowest possible score.
Time Frame	Experimental Night (Night 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group: Schizophrenia	Group: Healthy Controls
Arm/Group Description	Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants completed both the Drug and Placebo arms.	Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use. Participants completed both the Drug and Placebo arms.
Measure Participants	26	29
Placebo (Placebo capsule)	13.35 (15.62)	15.1 (12.22)
Drug (3mg eszopiclone)	9.69 (17.53)	16.69 (17.14)

Adverse Events

Time Frame	through study completion
Arm/Group Title	Placebo With Schizophrenia		Placebo Healthy Controls		3mg Eszopiclone With Schizophrenia		3mg Eszopiclone Healthy Controls
Arm/Group Description	Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants who completed Placebo Intervention.		Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use.Participants who completed Placebo Intervention.		Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants who completed Drug Intervention.		Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use.Participants who completed Drug Intervention.
All Cause Mortality
	Placebo With Schizophrenia		Placebo Healthy Controls		3mg Eszopiclone With Schizophrenia		3mg Eszopiclone Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/31 (0%)		0/28 (0%)		0/31 (0%)
Serious Adverse Events
	Placebo With Schizophrenia		Placebo Healthy Controls		3mg Eszopiclone With Schizophrenia		3mg Eszopiclone Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/31 (0%)		0/28 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Placebo With Schizophrenia		Placebo Healthy Controls		3mg Eszopiclone With Schizophrenia		3mg Eszopiclone Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/31 (0%)		0/28 (0%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.