Sequenced Therapies for Comorbid and Primary Insomnias

NCT01651442 | Completed Results DMC

• 2 other identifiers: R01MH091053-01R01MH091075
• Study Type: interventional
• Target: 211
• Locations: 2 countries
• Sites: 2

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.

Conditions

Insomnia Comorbid to Psychiatric Disorder; Primary Insomnia

Outcome Measures

Primary Outcomes (1)

• Percent of Participants Who Met Remission as Measured by the Insomnia Severity Index

  The Insomnia Severity Index (ISI) is a self-report questionnaire assessing the nature, severity, and impact of insomnia. Remission is determined to be a score less-than 8.

  6 weeks, 12 weeks, 3 months, 6 months, 9 months & 12 months

Study Arms (6)

Non-drug Sleep Therapy 1

ACTIVE COMPARATOR

Behavioral: Behavioral Insomnia Therapy

Sleep Medication 1

ACTIVE COMPARATOR

Drug: Zolpidem

Non-drug Sleep Therapy 2 Following Non-drug Sleep Therapy 1

ACTIVE COMPARATOR

Behavioral: Cognitive Therapy

Sleep Medication 2 Following Sleep Medication 1

ACTIVE COMPARATOR

Drug: Trazodone

Non-drug Sleep Therapy 1 Following Sleep Medication 1

ACTIVE COMPARATOR

Behavioral: Behavioral Insomnia Therapy

Sleep Medication 1 Following Non-drug Sleep Therapy 1

ACTIVE COMPARATOR

Drug: Zolpidem

Interventions

Behavioral Insomnia Therapy BEHAVIORAL

Sleep hygiene, stimulus control, and sleep restriction presented in four sessions.

Non-drug Sleep Therapy 1; Non-drug Sleep Therapy 1 Following Sleep Medication 1

Zolpidem DRUG

5mg or 10mg

Sleep Medication 1; Sleep Medication 1 Following Non-drug Sleep Therapy 1

Trazodone DRUG

50mg to 150mg

Sleep Medication 2 Following Sleep Medication 1

Cognitive Therapy BEHAVIORAL

Cognitive restructuring, constructive worry, behavioral experiments presented in four sessions.

Non-drug Sleep Therapy 2 Following Non-drug Sleep Therapy 1

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Jack Edinger, PhD: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Université Laval

Québec, Quebec, Canada

Location

Related Publications (4)

• Morin CM, Chen SJ, Ivers H, Beaulieu-Bonneau S, Krystal AD, Guay B, Belanger L, Cartwright A, Simmons B, Lamy M, Busby M, Edinger JD. Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions: A Randomized Clinical Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2349638. doi: 10.1001/jamanetworkopen.2023.49638.

  PMID: 38153735 DERIVED

• Edinger JD, Beaulieu-Bonneau S, Ivers H, Guay B, Belanger L, Simmons B, Morin CM. Association between insomnia patients' pre-treatment characteristics and their responses to distinctive treatment sequences. Sleep. 2022 Jan 11;45(1):zsab245. doi: 10.1093/sleep/zsab245.

  PMID: 34792177 DERIVED

• Morin CM, Edinger JD, Beaulieu-Bonneau S, Ivers H, Krystal AD, Guay B, Belanger L, Cartwright A, Simmons B, Lamy M, Busby M. Effectiveness of Sequential Psychological and Medication Therapies for Insomnia Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2020 Nov 1;77(11):1107-1115. doi: 10.1001/jamapsychiatry.2020.1767.

  PMID: 32639561 DERIVED

• Morin CM, Edinger JD, Krystal AD, Buysse DJ, Beaulieu-Bonneau S, Ivers H. Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial. Trials. 2016 Mar 3;17(1):118. doi: 10.1186/s13063-016-1242-3.

  PMID: 26940892 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Zolpidem; Trazodone; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Pyridones; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Bryan Simmons
• Organization: National Jewish Health

simmonsb@njhealth.org

303-398-1850

Study Officials

• Jack Edinger, PhD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Charles Morin, PhD

  Universite Laval

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: July 27, 2012
• Study Start: August 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 29, 2021
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Locations

CA (1); US (1)