Clinical trial NCT04468776: CBT-I or Zolpidem/Trazodone for Insomnia
Official title: Comparative Effectiveness of Zolpidem/Trazodone and Cognitive Behavioral Therapy for Insomnia in Rural Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Insomnia
Keywords: Insomnia
Chronic Insomnia
Zolpidem
Ambien
Cognitive-behavioral therapy for insomnia
CBT-I
Rural
Primary Care
Pragmatic Clinical Trial
Comparative Effectiveness
Trazodone
Lead sponsor: California Pacific Medical Center Research Institute
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: University of Pittsburgh
name: University of Arizona
name: University of Virginia
name: University of Illinois at Chicago
First posted: 2020-07-13
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 155 men and women aged 18-80 years living in rural areas.
Primary purpose: TREATMENT

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 155 participants will be enrolled and randomized in the United States. This trial is funded by the Patient-Centered Outcomes Research Institute.

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 6 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. COZI will study 155 patients recruited from 7 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.

Eligibility 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

Primary outcomes:
measure: Change in Insomnia Symptom Severity
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Number of Participants With Treatment Response of Insomnia Symptoms
timeFrame: Baseline, 6 months
measure: Number of Participants With Remission of Insomnia Symptoms
timeFrame: 6 months
Other outcomes:
measure: Change in Anxiety and Depression
timeFrame: Baseline, 6 months
measure: Change in Cognitive Function
timeFrame: Baseline, 6 months
measure: Change in Patient-Reported Health
timeFrame: Baseline, 6 months
measure: Change in Fatigue
timeFrame: Baseline, 6 months
measure: Change in Pain Intensity and Interference
timeFrame: Baseline, 6 months
measure: Change in Pittsburgh Sleep Quality Index
timeFrame: Baseline, 6 months
measure: Change in Daytime Sleepiness
timeFrame: Baseline, 6 months
measure: Change in Munich Chronotype
timeFrame: Baseline, 6 months
measure: Dysfunctional Beliefs and Attitudes About Sleep
timeFrame: Baseline, 6 months
measure: Number of Participants With Insomnia Treatment Side Effects
timeFrame: 1 month, 9 weeks, 6 months
measure: Medication Adherence
timeFrame: 1 month, 9 weeks, 6 months, 9 months, 12 months
measure: Self-reported Falls
timeFrame: 1 month, 9 weeks, 6 months
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: California Pacific Medical Center/Sutter Bay Hospitals
name: Katie L. Stone, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Daniel J. Buysse, MD
role: PRINCIPAL_INVESTIGATOR
References: