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CBT-I or Zolpidem/Trazodone for Insomnia (COZI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04468776
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : June 14, 2022
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
University of Pittsburgh
University of Arizona
University of Virginia
University of Illinois at Chicago
Information provided by (Responsible Party):
California Pacific Medical Center Research Institute

Brief Summary:
This study is a randomized (1:1:1) comparative effectiveness trial of medication (zolpidem or trazodone), cognitive-behavioral therapy for insomnia (CBT-I), and the combination (medication + CBT-I) for the treatment of chronic insomnia in men and women aged 18-80 living in rural areas with 1 year of follow-up. A total of 1200 participants will be enrolled and randomized in the United States. This trial is funded by the Patient-Centered Outcomes Research Institute.

Condition or disease Intervention/treatment Phase
Chronic Insomnia Drug: Zolpidem Behavioral: Internet Cognitive Behavioral Therapy for Insomnia (CBT-I) Drug: Trazodone Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study is a randomized (1:1:1) comparative effectiveness trial of medication preference (zolpidem or trazodone), CBT-I, and the combination for the treatment of insomnia in 1200 men and women aged 18-80 years living in rural areas.
Masking: Double (Investigator, Outcomes Assessor)
Masking Description: Masking of participants and providers is not possible given two very different treatment types. The Prime Principal Investigator and a statistician at the Data Coordinating Center will be masked to individual treatment assignment.
Primary Purpose: Treatment
Official Title: Comparative Effectiveness of Zolpidem/Trazodone and Cognitive Behavioral Therapy for Insomnia in Rural Adults
Actual Study Start Date : February 25, 2022
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : May 2025


Arm Intervention/treatment
Active Comparator: Medication (zolpidem or trazodone)
Zolpidem or trazodone, as prescribed by physician
Drug: Zolpidem
Zolpidem, as prescribed by physician
Other Name: Ambien

Drug: Trazodone
Trazodone, as prescribed by physician
Other Name: Desyrel

Active Comparator: Internet Cognitive Behavioral Therapy for Insomnia (CBT-I)
Internet-based CBT-I program
Behavioral: Internet Cognitive Behavioral Therapy for Insomnia (CBT-I)
6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention
Other Name: SHUTi

Experimental: Combination
Medication (zolpidem or trazodone) as prescribed by physician and Internet-based CBT-I program
Drug: Zolpidem
Zolpidem, as prescribed by physician
Other Name: Ambien

Behavioral: Internet Cognitive Behavioral Therapy for Insomnia (CBT-I)
6-week internet CBT-I multi-component intervention (SHUTi) including sleep restriction, stimulus control, cognitive restructuring, sleep behaviors, and relapse prevention
Other Name: SHUTi

Drug: Trazodone
Trazodone, as prescribed by physician
Other Name: Desyrel




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.


  2. 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.

  3. 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).

  4. 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.

  5. 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.


  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.


  11. 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.

  12. 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.

  13. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04468776


Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Stephen J. Thomas, PhD    205-934-3367    sjthoma@uabmc.edu   
Principal Investigator: Stephen J. Thomas, PhD         
United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 85721
Contact: Sairam Parthasarathy, MD    520-626-8309    sparthasarathy@deptofmed.arizona.edu   
Principal Investigator: Sairam Parthasarathy, MD         
United States, California
University of California, San Francisco-Fresno Active, not recruiting
Fresno, California, United States, 93701
United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Ann Depew, MA    303-398-1149    depewa@njhealth.org   
Principal Investigator: Jack D. Edinger, PhD         
United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65212
Contact: Christina McCrae, PhD    573-882-0982    mccraec@health.missouri.edu   
Principal Investigator: Christina McCrae, PhD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Asha Singh, MD    503-494-6066    singas@ohsu.edu   
Principal Investigator: Asha Singh, MD         
United States, Pennsylvania
Penn State Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Julio Fernandez-Mendoza, PhD, DBSM    717-531-6385    jfernandezmendoza@pennstatehealth.psu.edu   
Principal Investigator: Julio Fernandez-Mendoza, PhD, DBSM         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Daniel J. Buysse, MD    412-246-6413    buyssedj@upmc.edu   
Principal Investigator: Daniel J. Buysse, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Eric M. Davis, MD    434-982-0405    Emd9b@virginia.edu   
Principal Investigator: Eric M. Davis, MD         
Sponsors and Collaborators
California Pacific Medical Center Research Institute
Patient-Centered Outcomes Research Institute
University of Pittsburgh
University of Arizona
University of Virginia
University of Illinois at Chicago
Investigators
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Principal Investigator: Katie L. Stone, PhD California Pacific Medical Center/Sutter Bay Hospitals
Principal Investigator: Daniel J. Buysse, MD University of Pittsburgh
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Responsible Party: California Pacific Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT04468776    
Other Study ID Numbers: CER-2018C2-13262
CER-2018C2-13262 ( Other Grant/Funding Number: Patient-Centered Outcomes Research Institute )
First Posted: July 13, 2020    Key Record Dates
Last Update Posted: June 14, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by California Pacific Medical Center Research Institute:
Insomnia
Chronic Insomnia
Zolpidem
Ambien
Cognitive-behavioral therapy for insomnia
CBT-I
Rural
Primary Care
Pragmatic Clinical Trial
Comparative Effectiveness
Trazodone
Additional relevant MeSH terms:
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Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders
Zolpidem
Trazodone
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
GABA-A Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents