- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04468776
CBT-I or Zolpidem/Trazodone for Insomnia (COZI)
Comparative Effectiveness of Zolpidem/Trazodone and Cognitive Behavioral Therapy for Insomnia in Rural Adults
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Insomnia is a common health problem that causes distress, impaired function, and increased risk for other health problems. Chronic insomnia is defined by problems with the quality or amount of sleep, including difficulty falling asleep, frequent awakenings, and/or awakening early and being unable to return to sleep. In developing this application, patients, providers, payors, and the investigators identified both concerns and opportunities with current treatments for chronic insomnia. Medications and Cognitive-Behavioral therapy for insomnia (CBT-I; a treatment program to improve sleep through changes in behavior and thinking) are both effective for treating insomnia. Zolpidem, the most frequently prescribed insomnia medication, is widely available, but may cause side effects and dependency. Trazodone is increasingly prescribed off-label for treatment of insomnia, but evidence of efficacy and safety is more limited. CBT-I is the recommended first line treatment by many professional organizations, but it is not widely available in physicians' practices. Patients, providers, and payors face important unanswered questions: Which treatment should be used for the treatment of chronic insomnia? Is combination therapy more effective, and does it result in lower zolpidem use? Who responds best to which treatment? These dilemmas are particularly relevant to patients and providers in rural areas, where access to behavioral health specialists is limited, and concerns regarding use of controlled substances is particularly acute.
To address these questions, we propose the study, Comparative Effectiveness of Zolpidem/Trazodone and Cognitive Behavioral Therapy for Insomnia in Rural Adults (COZI). The investigators will use a well-tested Internet version of CBT-I, which is just as effective as in-person CBT-I, but more widely available. The aims of COZI are to: 1: Compare the effectiveness of medication preference (zolpidem or trazodone), CBT-I, and combination treatment for insomnia symptoms over 12 months. 2: Compare the effectiveness of medication preference, CBT-I, and combination treatment for other symptoms and problems, including health-related quality of life, mood, and health outcomes. 3: Compare the side effects of medication preference, CBT-I, and combination treatment. 4: Conduct an exploratory analysis of heterogeneity of treatment effects for common factors (age, gender, socio-economic status, degree or rurality, and other factors). COZI will study 1200 patients (400 per treatment) recruited from 8 health care systems across the country, each of which has established practices in rural areas. Patients will be treated with medication prescribed by their own physician (zolpidem or trazodone), Internet CBT-I, or a combination of the two. The investigators will evaluate treatment effects at 9 weeks, and 6 and 12 months (with limited additional assessments for adverse events and medication use at 1 and 9 months). Our study questions and design reflect early and ongoing engagement of key stakeholders including patients, providers, and payors, who are members of the Study Advisory Committee (SAC). SAC members will work with study investigators to recommend the best strategies for recruiting patients, measuring treatment effects, and disseminating study findings. The SAC will meet quarterly. Patients and other stakeholders have already provided guidance on which treatments are most worth studying, and which symptoms would best reflect the effects of treatment. Patients and other stakeholders will also be part of the Steering Committee, which is the main decision-making group for our study, and which will meet monthly. COZI will lead to answers for patients and providers addressing insomnia; improved health and function for millions of rural Americans; and sustainable changes in how insomnia is treated in rural practices.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35233
- University of Alabama at Birmingham
-
-
Arizona
-
Tucson, Arizona, United States, 85721
- University of Arizona
-
-
California
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Fresno, California, United States, 93701
- University of California, San Francisco-Fresno
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San Francisco, California, United States, 94158
- Sutter Health
-
-
Colorado
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Denver, Colorado, United States, 80206
- National Jewish Health
-
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Missouri
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Columbia, Missouri, United States, 65212
- University of Missouri
-
-
Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
-
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Penn State Hershey Medical Center
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh
-
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Virginia
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Charlottesville, Virginia, United States, 22908
- University of Virginia
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 18-80
- Insomnia Severity Index score > 10
- Regular internet and computer access
- Receives primary care in a Non-metropolitan/Rural residence
Exclusion Criteria:
- Use of hypnotic medication >2 times in the past week
- Current cognitive or cognitive behavioral treatment for insomnia
- Psychotic disorder
- Bipolar disorder
- Current substance use disorder
- Severe Chronic obstructive pulmonary disease (COPD) or other severe pulmonary disease (such as asthma or lung fibrosis)
- Cognitive impairment or dementia
- History of spontaneous or hypnotic-induced complex sleep behavior
- Delayed sleep phase disorder (DSPD)
- Shift work that includes working the night shift (between the hours of 12:00 a.m. - 6:00 a.m.)
- History of fracture or injurious fall in the past 12 months
- Currently pregnant, planning to become pregnant, or breastfeeding
- Other severe or uncontrolled mental or physical disorders that would make participation difficult or unsafe
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Medication (zolpidem or trazodone)
Zolpidem or trazodone, as prescribed by physician
|
Zolpidem, as prescribed by physician
Other Names:
Trazodone, as prescribed by physician
Other Names:
|
Active Comparator: Internet Cognitive Behavioral Therapy for Insomnia (CBT-I)
Internet-based CBT-I program
|
6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention
Other Names:
|
Experimental: Combination
Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program
|
Zolpidem, as prescribed by physician
Other Names:
Trazodone, as prescribed by physician
Other Names:
6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insomnia Symptoms
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
Change in Insomnia Severity Index score from baseline to follow-up.
The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks.
Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms.
|
Baseline, 9 weeks, 6 months, 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment Response of Insomnia Symptoms
Time Frame: 9 weeks, 6 months, 12 months
|
Treatment response defined as a ≥6 point reduction in Insomnia Severity Index score from baseline to follow-up.
The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks.
Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms.
|
9 weeks, 6 months, 12 months
|
Remission of Insomnia Symptoms
Time Frame: 9 weeks, 6 months, 12 months
|
Remission of Insomnia defined as Insomnia Severity Index <8 at follow-up.
The Insomnia Severity Index is a 7-item self-report questionnaire that measures severity of insomnia symptoms during the last two weeks.
Each item is scored 0 (no problem) to 4 (very severe problem) and total between 0-28, with higher scores indicating more severe insomnia symptoms.
|
9 weeks, 6 months, 12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anxiety and Depression
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The Patient Health Questionnaire (PHQ-8) is an 8-item self-report measure for assessing depression severity. The items are summed to yield a score between 0 and 24, with higher scores indicating more frequent depression symptoms. The Generalized Anxiety Disorder (GAD) Scale is a 7-item self-report measure used for screening and assessing severity of GAD. The items are summed to yield a score between 0 and 21, with higher scores indicating more severe GAD symptoms. |
Baseline, 9 weeks, 6 months, 12 months
|
Pittsburgh Sleep Quality Index
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The Pittsburgh Sleep Quality Index (PSQI) is an 18-item self-report measure that assesses sleep quality in the past month.
These items are combined into seven component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction).
The seven component scores are added to produce a global sleep quality score ranging from 0 to 21.
Higher global scores reflect lower sleep quality.
|
Baseline, 9 weeks, 6 months, 12 months
|
Daytime Sleepiness
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The Epworth Sleepiness Scale (ESS) is an 8-item self-report measure that assesses daytime sleepiness by asking about the likelihood of dozing in certain situations.
Individual items are summed to yield the ESS score between 0 (never doze) to 24 (doze a lot).
|
Baseline, 9 weeks, 6 months, 12 months
|
Cognitive Function
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The PROMIS Cognitive Function Short Form (8a) is an 8-item self-report measure related to executive functioning.
Individual item responses range from 1 (very often) to 5 (never) with higher scores signifying higher cognitive function.
|
Baseline, 9 weeks, 6 months, 12 months
|
Patient-Reported Health
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The PROMIS Global Health is a 10-item self-report measure that assess general domains of health and functioning. Individual item responses range from 1 (excellent/none) to 5 (poor/always) and a single pain item ranges from 0 (no pain) to 10 (worst pain). Lower scores indicate greater health-related quality of life. The Medical Outcome Survey (SF-12) is a 12-item self-report measure of physical and mental health. Scores can be expressed with two component scores: Physical Component Score (PCS) and Mental Component Score (MCS). The component scores can range from 0 to 100, with higher scores indicating better health. |
Baseline, 9 weeks, 6 months, 12 months
|
Insomnia Treatment Side Effects
Time Frame: 1 month, 9 weeks, 6 months, 9 months, 12 months
|
Side effects (frequency, severity, impairment) are recorded via self-report adapted from the FIBSER.
Scores range from 0 (no side effects; better) to 21 (worse).
Those reporting severity of greater than moderate and/or frequency greater than 50% of the time in their self-report, or who spontaneously report a side effect, are contacted by the study coordinator.
Information is gathered regarding the nature and duration of the event and action taken.
Determination of causality and outcomes attributed to the event are then made.
|
1 month, 9 weeks, 6 months, 9 months, 12 months
|
Falls
Time Frame: Baseline, 1 month, 9 weeks, 6 months, 9 months, 12 months
|
Falls are reported via self-report, including context, location, and consequences of falls.
Those reporting two or more falls, or a fall resulting in medical care, are contacted by the study coordinator.
Information is gathered regarding the nature and duration of the event and action taken.
Determination of causality and outcomes attributed to the event are then made.
|
Baseline, 1 month, 9 weeks, 6 months, 9 months, 12 months
|
Medications
Time Frame: Baseline, 1 month, 9 weeks, 6 months, 9 months, 12 months
|
Medication use is assessed using self-reported prescription, over-the-counter, and supplement name and frequency.
|
Baseline, 1 month, 9 weeks, 6 months, 9 months, 12 months
|
Fatigue
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The PROMIS Fatigue instrument is a 7-item self-report measure that assesses recent fatigue and how fatigue interfered with daily activities.
Scores range from 7 to 35, with higher scores indicating greater fatigue.
|
Baseline, 9 weeks, 6 months, 12 months
|
Pain Intensity and Interference
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The PROMIS Pain Intensity scale is a 3-item instrument used to assess how much pain a person has. Scores range from 3-15, with higher scores indicating greater pain intensity. The PROMIS Pain Interference scale is a 6-item instrument used to assess the consequences of pain in different domains of daily life. Scores range from 6-30, with higher scores indicating greater interference. |
Baseline, 9 weeks, 6 months, 12 months
|
Munich Chronotype Questionnaire
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
The Munich Chronotype Questionnaire (MCTQ) is a self-report scale to assess sleep structure, patterns, duration, and quality.
Scores range from 16 to 86, with the lower scores representing later chronotypes.
|
Baseline, 9 weeks, 6 months, 12 months
|
Dysfunctional Beliefs and Attitudes about Sleep
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale is a 16-item instrument used to evaluate dysfunctional thoughts related to insomnia.
Each item is scored 0-10 and the total is the average of the 16 item scores (range 0-10), with higher scores indicating greater dysfunctional beliefs about sleep.
|
Baseline, 9 weeks, 6 months, 12 months
|
Other factors that may affect treatment response (exploratory)
Time Frame: Baseline, 9 weeks, 6 months, 12 months
|
Sleep diary, Covid-19, nocturia symptoms, treatment expectancy, treatment satisfaction, tobacco use, alcohol use, caffeine use, demographics, and medical history.
|
Baseline, 9 weeks, 6 months, 12 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Daniel J. Buysse, MD, University of Pittsburgh
- Principal Investigator: Katie L. Stone, PhD, California Pacific Medical Center/Sutter Bay Hospitals
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Wake Disorders
- Sleep Initiation and Maintenance Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Tranquilizing Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Hypnotics and Sedatives
- Anti-Anxiety Agents
- GABA Agents
- Antidepressive Agents, Second-Generation
- Sleep Aids, Pharmaceutical
- GABA-A Receptor Agonists
- GABA Agonists
- Selective Serotonin Reuptake Inhibitors
- Zolpidem
- Trazodone
Other Study ID Numbers
- CER-2018C2-13262 (Other Grant/Funding Number: Patient-Centered Outcomes Research Institute)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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