Sleep DisordersPhase 4NCT00177216
Characteristics of Sleep Patterns in Young Adults With and Without Insomnia
A Phase 4 study testing Zolpidem and Escitalopram in people with Sleep Disorders, run by University of Pittsburgh at 1 site in United States.
Trial summary
This study will compare the symptoms, experiences, and laboratory sleep characteristics of young adults with and without insomnia. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Sleep Disorders
- What is being tested?
- Zolpidem and Escitalopram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2002to May 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Physically healthy
- Meets DSM-IV criteria for primary insomnia
- For subjects interested in PET study only: right-handedness
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Western Psychiatric Institute and Clinic/ University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Psychobiology and Treatment Response in Primary Insomnia
This study will compare the symptoms, experiences, and laboratory sleep characteristics of young adults with and without insomnia.
Read the detailed description
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
- Sleep Disorders
- Being tested
- Zolpidem, Escitalopram, Placebo
- Keywords
- Primary Insomnia, Insomnia, Placebo-Controlled, Double-Blind, Polysomnography, PET Studies, Escitalopram, Zolpidem
- Medical subject headings
- Sleep Wake Disorders, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZolpidemDrug
Also called Ambien
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.
EscitalopramDrug
Also called Celexa
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.
PlaceboDrug
Also called Placebo control
A placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime.
| Study group | Role | What they receive |
|---|---|---|
| Zolpidem | Experimental | 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. Receives: Drug: Escitalopram |
| Excitalopram | Experimental | 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. Receives: Drug: Zolpidem |
| Placebo | Placebo comparator | A placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pittsburgh Sleep Quality Index
Self-report measure of sleep quality developed at University of Pittsburgh by Daniel J. Buysse, M.D. The PSQI total score ranges from 0 to 21 with 0 being marvelous sleep and 21 being horrid sleep. The difference score, reported below, is the total score after at least 5 weeks of treatment in one of the three arms, minus the baseline total score. A negative score means that the sleep of the participant improved.
Measured: post treatment minus baseline assessment battery. This averaged 100 days.
Change in Diary Sleep Efficiency
The change in self-report sleep efficiency calculated from 7-day sleep diary (DSE): Sleep efficiency is the percent of (time spent asleep divided by the amount of time between good night time and final awakening). It ranges from 0 (no sleep at all) to 100 (asleep the second your head hits the pillow until you wake up in the morning and get out of bed). Participants report the time they go to bed, how long they think it takes them to fall asleep, how many minutes they are awake during the night, and then what time they finally wake up in the morning. These values are used to calculate the diary sleep efficiency for each night and then we averaged these across the 7 days of diary collected pre and post treatment. The values below are post treatment DSE minus pre treatment DSE. A positive number means that the DSE was higher (better) post treatment.
Measured: post treatment minus baseline. This averaged 69 days.
Secondary outcomes (1)
Change in PSG Sleep Efficiency for the Second Night in the Sleep Lab at Each Timepoint
Change in PSG Sleep Efficiency (SE) between post-treatment and baseline: Sleep efficiency is the percent of time spent asleep divided by the total sleep recording period in the sleep lab. This value is calculated using the results of the polysomnographic sleep study. It ranges from 0 (no sleep at all) to 100 (asleep the second the sleep recording starts (GNT) until the sleep recording ends (GMT) in the morning). The values below are post treatment SE minus pre treatment SE. A positive number means that the SE was higher (better) post treatment.
Measured: post treatment minus baseline PSG sleep studies. This averaged 70 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startFeb 2002
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sleep DisordersStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Daniel J. Buysse, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00177216
- Sponsor's protocol ID
- R01MH024652
- Other IDs
- R01MH024652, 010807
- Status last verified
- Feb 2016
- First submitted
- 12 Sep 2005
- Last updated
- 30 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: To gain access to data, researchers must submit a description of their project to the Principal Investigator, including the investigator's personal identification and institutional affiliation, a current CV, qualifications, duration of the proposed research, source of funding, and a conflict of interest statement. The protocol must include study aims, background and significance, methods and types of analysis, and a description of the data requested. Once approved, the investigator must complete a University of Pittsburgh IRB exempt research application form and document completion of a responsible conduct of research program. Data will be prepared by an 'honest broker' from the data management staff of the project. This person will complete the honest broker certification form required by our IRB. Data will be provided as a SAS data set, and will not include information that could identify individual research participants or that the original consent form expressly forbade.
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychobiology and Treatment Response in Primary Insomnia
- ClinicalTrials.gov ID
- NCT00177216
- Acronym / sponsor ID
- R01MH024652
- Conditions
- Sleep Disorders
- Keywords
- Primary Insomnia, Insomnia, Placebo-Controlled, Double-Blind, Polysomnography, PET Studies, Escitalopram, Zolpidem
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2002
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 30 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare the symptoms, experiences, and laboratory sleep characteristics of young adults with and without insomnia.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Zolpidem | Experimental | Drug: EscitalopramThe 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. |
| Excitalopram | Experimental | Drug: ZolpidemThe 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. |
| Placebo | Placebo comparator | Drug: PlaceboA placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Physically healthy
- Meets DSM-IV criteria for primary insomnia
- For subjects interested in PET study only: right-handedness
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZolpidemAlso: AmbienThe 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. | Drug | Excitalopram |
| EscitalopramAlso: CelexaThe 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. | Drug | Zolpidem |
| PlaceboAlso: Placebo controlA placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime. | Drug | Placebo |
Primary outcome
Change in Pittsburgh Sleep Quality Index
Time frame: post treatment minus baseline assessment battery. This averaged 100 days.
Self-report measure of sleep quality developed at University of Pittsburgh by Daniel J. Buysse, M.D. The PSQI total score ranges from 0 to 21 with 0 being marvelous sleep and 21 being horrid sleep. The difference score, reported below, is the total score after at least 5 weeks of treatment in one of the three arms, minus the baseline total score. A negative score means that the sleep of the participant improved.
Change in Diary Sleep Efficiency
Time frame: post treatment minus baseline. This averaged 69 days.
The change in self-report sleep efficiency calculated from 7-day sleep diary (DSE): Sleep efficiency is the percent of (time spent asleep divided by the amount of time between good night time and final awakening). It ranges from 0 (no sleep at all) to 100 (asleep the second your head hits the pillow until you wake up in the morning and get out of bed). Participants report the time they go to bed, how long they think it takes them to fall asleep, how many minutes they are awake during the night, and then what time they finally wake up in the morning. These values are used to calculate the diary sleep efficiency for each night and then we averaged these across the 7 days of diary collected pre and post treatment. The values below are post treatment DSE minus pre treatment DSE. A positive number means that the DSE was higher (better) post treatment.
1 secondary outcome
Change in PSG Sleep Efficiency for the Second Night in the Sleep Lab at Each Timepoint
Time frame: post treatment minus baseline PSG sleep studies. This averaged 70 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. To gain access to data, researchers must submit a description of their project to the Principal Investigator, including the investigator's personal identification and institutional affiliation, a current CV, qualifications, duration of the proposed research, source of funding, and a conflict of interest statement. The protocol must include study aims, background and significance, methods and types of analysis, and a description of the data requested. Once approved, the investigator must complete a University of Pittsburgh IRB exempt research application form and document completion of a responsible conduct of research program. Data will be prepared by an 'honest broker' from the data management staff of the project. This person will complete the honest broker certification form required by our IRB. Data will be provided as a SAS data set, and will not include information that could identify individual research participants or that the original consent form expressly forbade.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel J. Buysse, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zolpidem and Escitalopram in people with Sleep Disorders, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pittsburgh Sleep Quality Index (time frame: post treatment minus baseline assessment battery. This averaged 100 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2016.