Characteristics of Sleep Patterns in Young Adults With and Without Insomnia

NCT ID: NCT00177216

Last Updated: 2016-03-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-02-28

Study Completion Date

2008-05-31

Brief Summary

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This study will compare the symptoms, experiences, and laboratory sleep characteristics of young adults with and without insomnia.

Detailed Description

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The overall aim of this research study is to compare the symptoms, experiences and laboratory sleep characteristics of young adults with and without insomnia. Insomnia is a pattern of difficulty falling asleep, staying asleep or feeling poorly rested despite an adequate amount of time for sleep, which occurs nearly every night for one month or longer. For those with insomnia, we will look at the effects of an intervention with one of two medications (escitalopram or zolpidem) or an inactive pill (placebo). This intervention will be followed by re-evaluation of symptoms, experiences and laboratory sleep characteristics. The three hypotheses being investigated are: compared to control subjects, those with insomnia will demonstrate affective disturbance and heightened arousal; the different medications will have different degrees of effect on the two dimensions being measured (affective disturbance and heightened arousal); and PET scans will reveal different patterns of activity in the brains of groups of people with insomnia.

We will specifically focus on the syndrome of Primary Insomnia (PI), defined by DSM-IV as insomnia that lasts for at least one month and causes significant impairment or distress. PI excludes insomnia that occurs exclusively during the course of another sleep, mental, substance-induced, or medical disorder. Insomnia is a significant public health problem because of its prevalence, morbidity, and the risk it poses for the development of subsequent mental disorders, particularly depressive and anxiety disorders. Understanding the psychobiology of primary insomnia is a critical step toward addressing questions regarding its relationships with mood and anxiety disorders.

Our model of insomnia builds on two major concepts running through previous insomnia research, affective disturbance and heightened arousal, as driving factors for the sleep-wake disturbances that define PI. Implicit in this model is that individuals with PI have different degrees of each dysfunction, which accounts for their heterogeneity of clinical symptoms. Contemporary theories of affect structure suggest that these two dimensions may be orthogonal in pure form, but are nevertheless related in clinical conditions characterized by mixed anxiety-depression, such as PI. Measures of affective disturbance and arousal in this study will include questionnaires, diary-based assessments, and physiological measures.

Pharmacological treatment probes may help to further distinguish the roles of affective disturbance and heightened arousal in insomnia. We will use a benzodiazepine receptor agonist (BzRA), zolpidem, and an antidepressant, escitalopram. BzRA potentiate the effects of GABA (1), but have minimal direct activity at any other receptor types. They are efficacious treatments for insomnia (2-4), but have little effect on mood. We chose zolpidem because it is relatively specific for hypnotic versus anxiolytic or other actions (5), because it is the most widely-prescribed BzRA hypnotic, and because it is well-tolerated (6). Clinically-effective doses of even "nonsedating" antidepressants can also improve symptoms in PI (7), suggesting that direct sedation is not their only mechanism for improving insomnia. We chose escitalopram because it is neither strongly alerting nor sedating in clinical and polysomnographic studies. This "sleep-neutral" profile will allow us to use it for its effects on affective disturbance, rather than its nonspecific sedating properties. Escitalopram's specific effect on serotonin reuptake blockade and its lack of affinity for Bz receptors distinguish it from zolpidem as a pharmacologic probe.

Functional neuroimaging studies in wakefulness and sleep may also help to identify the substrate of affective disturbance and heightened arousal in insomnia. Affective disturbance in the form of MDD is associated with alterations in both regional deactivation patterns during NREM sleep, and regional activation patterns during REM sleep. These observations suggest that a sleep-wake functional neuroimaging paradigm in insomnia patients, in conjunction with behavioral measures, may help to identify which brain systems mediate heightened arousal and affective disturbance, and how these systems interact.

Conditions

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Sleep Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Zolpidem

The benzodiazepine receptor agonist (BzRA), zolpidem was given in an initial dose of 5 mg by mouth every night, 30 minutes prior to bedtime. The dose was increased to a maximum of 10 mg after the first week if there was no improvement in overall symptoms (CGI score of 4 or \>). The dose was decreased to 5 mg if side effects occurred.

Group Type EXPERIMENTAL

Escitalopram

Intervention Type DRUG

The antidepressant, escitalopram was initiated at 5 mg by mouth every night, 30 minutes prior to bedtime. If there were no side effects, the dose was increased every four days until the target dose of 20 mg (maximum dose) was reached by day 13. If significant side effects appeared, the highest tolerated dose was used.

Excitalopram

The antidepressant, escitalopram was initiated at 5 mg by mouth every night, 30 minutes prior to bedtime. If there were no side effects, the dose was increased every four days until the target dose of 20 mg (maximum dose) was reached by day 13. If significant side effects appeared, the highest tolerated dose was used.

Group Type EXPERIMENTAL

Zolpidem

Intervention Type DRUG

The benzodiazepine receptor agonist (BzRA), zolpidem was given in an initial dose of 5 mg by mouth every night, 30 minutes prior to bedtime. The dose was increased to a maximum of 10 mg after the first week if there was no improvement in overall symptoms (CGI score of 4 or \>). The dose was decreased to 5 mg if side effects occurred.

Placebo

A placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

A placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime.

Interventions

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Zolpidem

The benzodiazepine receptor agonist (BzRA), zolpidem was given in an initial dose of 5 mg by mouth every night, 30 minutes prior to bedtime. The dose was increased to a maximum of 10 mg after the first week if there was no improvement in overall symptoms (CGI score of 4 or \>). The dose was decreased to 5 mg if side effects occurred.

Intervention Type DRUG

Escitalopram

The antidepressant, escitalopram was initiated at 5 mg by mouth every night, 30 minutes prior to bedtime. If there were no side effects, the dose was increased every four days until the target dose of 20 mg (maximum dose) was reached by day 13. If significant side effects appeared, the highest tolerated dose was used.

Intervention Type DRUG

Placebo

A placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime.

Intervention Type DRUG

Other Intervention Names

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Ambien Celexa Placebo control

Eligibility Criteria

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Inclusion Criteria

* Physically healthy
* Meets DSM-IV criteria for primary insomnia
* For subjects interested in PET study only: right-handedness

Exclusion Criteria

* Currently taking antidepressants, antianxiety medications or medications for sleep disorders
* Currently experiencing symptoms of psychiatric disorders such as major depressive disorder, bipolar disorder, generalized anxiety disorder
* Significant or unstable acute or chronic medical conditions, such as seizure disorder, tumor, liver disease, active peptic ulcer disease, arthritis, irritable bowel disease
* Meets DSM-IV criteria for sleep apnea or periodic limb movement disorder
Minimum Eligible Age

20 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel J. Buysse, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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Western Psychiatric Institute and Clinic/ University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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R01MH024652

Identifier Type: NIH

Identifier Source: secondary_id

View Link

010807

Identifier Type: OTHER

Identifier Source: secondary_id

R01MH024652

Identifier Type: NIH

Identifier Source: org_study_id

View Link

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