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| Name | Class |
|---|---|
| Beth Israel Deaconess Medical Center | OTHER |
| Mclean Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Schizophrenia | Experimental | 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. |
|
| Healthy Controls | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| eszopiclone | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Sleep Spindle Density | 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. | Spindles will be averaged for the Baseline (Night 1) and Experimental Nights (Night 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Motor Procedural Memory Performance | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Dara S Manoach, Ph.D. | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
There is no plan to share IPD data.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group: Schizophrenia | Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants completed both the Drug and Placebo arms. |
| FG001 | Group: Healthy Controls | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
All participants completed both the Drug and Placebo arms
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| ID | Title | Description |
|---|---|---|
| BG000 | Group: Schizophrenia | Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants completed both the Drug and Placebo arms. |
| BG001 | Group: Healthy Controls |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Sleep Spindle Density | 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. | Posted | Mean | Standard Deviation | Sleep spindle density (number/minutes) | Spindles will be averaged for the Baseline (Night 1) and Experimental Nights (Night 2) |
|
through study completion
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo With Schizophrenia | Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants who completed Placebo Intervention. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dara S. Manoach, Principal Investigator | Massachusetts General Hospital | 617-724-6148 | dara.manoach@mgh.harvard.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000069582 | Eszopiclone |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011719 | Pyrazines |
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|
| placebo | Drug | 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 Night (Night 2) |
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.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Motor Procedural Memory Performance | 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. | Posted | Mean | Standard Deviation | percentage of improvement on MST perform | Experimental Night (Night 2) |
|
|
|
| 0 |
| 28 |
| 0 |
| 28 |
| 0 |
| 28 |
| EG001 | Placebo Healthy Controls | 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. | 0 | 31 | 0 | 31 | 0 | 31 |
| EG002 | 3mg Eszopiclone With Schizophrenia | Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. Participants who completed Drug Intervention. | 0 | 28 | 0 | 28 | 0 | 28 |
| EG003 | 3mg Eszopiclone Healthy Controls | 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. | 0 | 31 | 0 | 31 | 0 | 31 |
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| D011725 |
| Pyridines |