Sequenced Therapies for Comorbid and Primary Insomnias

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. Read our disclaimer for details. Identifier: NCT01651442
Recruitment Status : Active, not recruiting
First Posted : July 27, 2012
Last Update Posted : April 28, 2017
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Jack Edinger, PhD, National Jewish Health

Brief Summary:
Chronic insomnia is a prevalent disorder associated with increased health care costs, impaired functioning, and an increased risk for developing serious psychiatric disorders. Cognitive-behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported approaches for insomnia management. Unfortunately, few studies have compared the psychological/behavioral therapies and BzRAs for insomnia treatment. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose and fixed-agent pharmacotherapy strategies that do not represent usual adjustable dosing practices, relatively short follow-up intervals, and reliance on self-report or polysomnographic (PSG) sleep parameters as outcomes, rather than on more clinically relevant indicators of remission. Finally, studies have yet to test the benefits of treatment sequencing for those who do not respond to initial their insomnia therapy. This multi-site project will address these limitations. Two study sites will enroll a total of 224 participants who meet broad criteria for a chronic insomnia disorder, and a sizeable portion (60%) of this sample will have insomnia occurring comorbid to a psychiatric disorder. Participants will be evaluated with clinical assessments and PSG, and then will be randomly assigned to first-stage therapy with an easy-to-administer behavioral insomnia therapy (BT) or zolpidem (most widely prescribed BzRA). Centrally trained therapists will administer therapies according to manualized, albeit flexible, treatment algorithms. Initial outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered re-randomization to a second, 6-week treatment involving pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy-CT). All participants will be re-evaluated 12 weeks after protocol initiation, and at 3-, 6-, 9-, and 12-month follow-ups while continuing their final treatment. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, will serve as the primary outcome for treatment comparisons. Secondary outcomes will include sleep diary and PSG sleep measures; subjective ratings of sleep and daytime function; adverse events; dropout rates; and treatment acceptability. Our over-arching goal is to obtain new information that aids in the development of clinical guidelines for managing insomnia sufferers with and without comorbid psychiatric conditions.

Condition or disease Intervention/treatment Phase
Insomnia Comorbid to Psychiatric Disorder Primary Insomnia Behavioral: Behavioral Insomnia Therapy Drug: Zolpidem Drug: Trazodone Behavioral: Cognitive Therapy Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sequenced Therapies for Comorbid and Primary Insomnias
Actual Study Start Date : June 2011
Actual Primary Completion Date : February 28, 2017
Estimated Study Completion Date : July 2018

Arm Intervention/treatment
Active Comparator: Non-drug Sleep Therapy 1 Behavioral: Behavioral Insomnia Therapy
Sleep hygiene, stimulus control, and sleep restriction presented in four sessions.

Active Comparator: Sleep Medication 1 Drug: Zolpidem
5mg or 10mg

Active Comparator: Non-drug Sleep Therapy 2 Behavioral: Cognitive Therapy
Cognitive restructuring, constructive worry, behavioral experiments presented in four sessions.

Active Comparator: Sleep Medication 2 Drug: Trazodone
50mg to 150mg

Primary Outcome Measures :
  1. Insomnia Severity Index- Change from Baseline (Remission) [ Time Frame: 6 weeks, 12 weeks, 3 months, 6 months, 9 months & 12 months ]

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.

Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • a complaint of persistent (i.e., > 1 month) difficulties initiating or maintaining sleep despite adequate opportunity for sleep;
  • a sleep onset latency or wake time after sleep onset > 30 minutes 3 or more nights per week during two weeks sleep diary monitoring;
  • an Insomnia Severity Index (ISI) score > 10 indicating at least "mild" insomnia; and
  • a score ≥ 2 on either the interference or distress item of the screening ISI, indicating the insomnia causes significant distress or impairment in social, occupational, or other areas of functioning. These criteria represent those provided in the DSM-IV-TR87, Research Diagnostic Criteria3 and the International Classification of Sleep Disorders4, and will ensure a sample with clinically relevant insomnia.

Exclusion Criteria:

Exclusion criteria will be minimal to retain a broadly representative sample that includes patients with primary and insomnia comorbid to a psychiatric disorder. Likewise, individuals with a comorbid medical condition will be excluded only if the medical condition is life-threatening or would contra-indicate using study medications. Exclusion criteria are

  • an untreated psychiatric disorder (e.g., major depression) as these conditions have specific treatments and it would be inappropriate not to offer those treatments;
  • a lifetime diagnosis of any psychotic or bipolar disorder as sleep restriction and medications for insomnia may precipitate mania and hallucinations;
  • an imminent risk for suicide;
  • alcohol or drug abuse within the past year, since BzRAs are cross-tolerant with alcohol;
  • terminal or progressive physical illness (e.g., cancer, COPD), or neurological degenerative disease (e.g., dementia);
  • current use of medications known to cause insomnia (e.g., steroids);
  • sleep apnea (apnea/hypopnea index > 15), restless legs syndrome, periodic limb movement during sleep (PLMS with arousal > 15 per hour), or a circadian rhythm sleep disorder (e.g., advanced sleep phase syndrome);
  • habitual bedtimes later than 2:00 AM or rising times later than 10:00 AM;
  • consuming > 2 alcoholic beverages per day on a regular basis.

Individuals using sleep-aids (prescribed or over-the-counter) will be included if they are willing and able to discontinue medications at least 2 weeks before baseline assessment. Participants using alcohol as a sleep aid or alcohol after 7:00pm on a regular basis will be required to discontinue this practice at least two weeks prior to baseline assessment. Individuals using psychotropic medications (e.g., anxiolytics, antidepressants) will not be automatically excluded from the study. Those on stable dosages (for at least three months) of SSRI or SNRI medications and who show at least partial remission (via SCID) from their mood or anxiety disorder will be accepted in the study if they meet the selection criteria above. Patients using TCAs, MAOIs, or atypical antidepressants will be excluded even if in remission as the effects of these medications on sleep might confound interpretation of the findings. We will impose similar standards for those with MDD, dysthymia, panic disorder, phobia, and GAD. We realize that some decisions about enrollment may not always be easy to make, but we will rely on all available data and a consensus approach to guide our clinical decision making process

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 identifier (NCT number): NCT01651442

United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
Canada, Quebec
Université Laval
Quebec City, Quebec, Canada
Sponsors and Collaborators
Jack Edinger, PhD
National Institutes of Health (NIH)
Principal Investigator: Jack Edinger, PhD National Jewish Health
Principal Investigator: Charles Morin, PhD Universite Laval

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Jack Edinger, PhD, Principal Investigator, National Jewish Health Identifier: NCT01651442     History of Changes
Other Study ID Numbers: R01MH091053-01 ( U.S. NIH Grant/Contract )
First Posted: July 27, 2012    Key Record Dates
Last Update Posted: April 28, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Mental Disorders
Problem Behavior
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Behavioral Symptoms
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