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Sponsored by: |
National Institute of Mental Health (NIMH) |
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Information provided by: | National Institute of Mental Health (NIMH) |
ClinicalTrials.gov Identifier: | NCT00177216 |
This study will compare the symptoms, experiences, and laboratory sleep characteristics of young adults with and without insomnia.
Condition | Intervention | Phase |
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Sleep Disorders |
Drug: Escitalopram Drug: Zolpidem Drug: Placebo |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Psychobiology and Treatment Response in Primary Insomnia |
Estimated Enrollment: | 99 |
Study Start Date: | February 2002 |
Estimated Study Completion Date: | January 2028 |
Primary Completion Date: | May 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Participants receiving an enzodiazepine receptor agonist (BzRA), zolpidem
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Drug: Zolpidem
Benzodiazepine receptor agonist (BzRA), zolpidem, treatment for insomnia
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2: Experimental
Participants receiving an antidepressant, escitalopram
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Drug: Escitalopram
Antidepressant, escitalopram, treatment for insomnia
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3: Placebo Comparator
Participants receiving a placebo
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Drug: Placebo
Placebo control
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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.
Ages Eligible for Study: | 20 Years to 50 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
United States, Pennsylvania | |
Western Psychiatric Institute and Clinic/ University of Pittsburgh Medical Center | |
Pittsburgh, Pennsylvania, United States, 15213 |
Principal Investigator: | Daniel J. Buysse, MD | University of Pittsburgh |
Responsible Party: | University of Pittsburgh School of Medicine ( Daniel J. Buysse, MD ) |
Study ID Numbers: | R01 MH24652, 010807, DATR A2-AID |
Study First Received: | September 12, 2005 |
Last Updated: | August 20, 2008 |
ClinicalTrials.gov Identifier: | NCT00177216 |
Health Authority: | United States: Federal Government |
Primary Insomnia Insomnia Placebo-Controlled Double-Blind |
Polysomnography PET Studies Escitalopram Zolpidem |
Zolpidem Sleep Initiation and Maintenance Disorders Signs and Symptoms Mental Disorders Neurologic Manifestations Dyssomnias |
Sleep Disorders Dexetimide Citalopram Serotonin Sleep Disorders, Intrinsic |
Parasympatholytics Neurotransmitter Agents Neurotransmitter Uptake Inhibitors Cholinergic Antagonists Molecular Mechanisms of Pharmacological Action Anti-Dyskinesia Agents Physiological Effects of Drugs Psychotropic Drugs Antiparkinson Agents Cholinergic Agents Therapeutic Uses Hypnotics and Sedatives Antidepressive Agents, Second-Generation |
Antidepressive Agents Nervous System Diseases Central Nervous System Depressants Serotonin Uptake Inhibitors Pharmacologic Actions Muscarinic Antagonists Serotonin Agents Autonomic Agents GABA Agonists GABA Agents Peripheral Nervous System Agents Central Nervous System Agents |