Insomnia Comorbid to Psychiatric DisorderNCT01651442
Sequenced Therapies for Comorbid and Primary Insomnias
A study testing Behavioral Insomnia Therapy, Zolpidem and Trazodone in people with Insomnia Comorbid to Psychiatric Disorder and Primary Insomnia, run by Jack Edinger, PhD at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Insomnia Comorbid to Psychiatric Disorder, Primary Insomnia
- What is being tested?
- Behavioral Insomnia Therapy, Zolpidem and Trazodone
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 211 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Aug 2012to 1 Mar 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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.
- Being tested
- Behavioral Insomnia Therapy, Zolpidem, Trazodone, Cognitive Therapy
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Behavioral Insomnia TherapyBehavioural
Sleep hygiene, stimulus control, and sleep restriction presented in four sessions.
ZolpidemDrug
5mg or 10mg
TrazodoneDrug
50mg to 150mg
Cognitive TherapyBehavioural
Cognitive restructuring, constructive worry, behavioral experiments presented in four sessions.
| Study group | Role | What they receive |
|---|---|---|
| Non-drug Sleep Therapy 1 | Active comparator | Not described Receives: Behavioral: Behavioral Insomnia Therapy |
| Sleep Medication 1 | Active comparator | Not described Receives: Drug: Zolpidem |
| Non-drug Sleep Therapy 2 Following Non-drug Sleep Therapy 1 | Active comparator | Not described Receives: Behavioral: Cognitive Therapy |
| Sleep Medication 2 Following Sleep Medication 1 | Active comparator | Not described Receives: Drug: Trazodone |
| Non-drug Sleep Therapy 1 Following Sleep Medication 1 | Active comparator | Not described Receives: Behavioral: Behavioral Insomnia Therapy |
| Sleep Medication 1 Following Non-drug Sleep Therapy 1 | Active comparator | Not described Receives: Drug: Zolpidem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks, 12 weeks, 3 months, 6 months, 9 months & 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2012 (estimated)
- Study start1 Aug 2012
- Primary completion1 Mar 2017
- Study completion1 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Insomnia Comorbid to Psychiatric DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jack Edinger, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Jack Edinger, PhD, National Jewish Health
- Investigators
- Jack Edinger, PhD, Principal investigator, National Jewish HealthCharles Morin, PhD, Principal investigator, Universite Laval
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01651442
- Sponsor's protocol ID
- R01MH091053-01
- Other IDs
- R01MH091075
- Status last verified
- Aug 2019
- First submitted
- 26 Jun 2012
- Last updated
- 29 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 38153735Edinger 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.
PubMed 34792177Morin 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.
PubMed 32639561Morin 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.
PubMed 26940892
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequenced Therapies for Comorbid and Primary Insomnias
- ClinicalTrials.gov ID
- NCT01651442
- Acronym / sponsor ID
- R01MH091053-01
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 211 participants (actual)
- Lead sponsor
- Jack Edinger, PhDUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Study start
- 1 Aug 2012 (actual)
- Primary completion
- 1 Mar 2017 (actual)
- Study completion
- 1 Mar 2017 (actual)
- First posted
- 27 Jul 2012 (estimated)
- Results
- Posted 28 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Behavioral Insomnia TherapySleep hygiene, stimulus control, and sleep restriction presented in four sessions. | Behavioural | Non-drug Sleep Therapy 1, Non-drug Sleep Therapy 1 Following Sleep Medication 1 |
| Zolpidem5mg or 10mg | Drug | Sleep Medication 1, Sleep Medication 1 Following Non-drug Sleep Therapy 1 |
| Trazodone50mg to 150mg | Drug | Sleep Medication 2 Following Sleep Medication 1 |
| Cognitive TherapyCognitive restructuring, constructive worry, behavioral experiments presented in four sessions. | Behavioural | Non-drug Sleep Therapy 2 Following Non-drug Sleep Therapy 1 |
Primary outcome
Percent of Participants Who Met Remission as Measured by the Insomnia Severity Index
Time frame: 6 weeks, 12 weeks, 3 months, 6 months, 9 months & 12 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38153735Morin 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.
- Derived from this study: PubMed 34792177Edinger 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.
- Derived from this study: PubMed 32639561Morin 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.
- Derived from this study: PubMed 26940892Morin 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.
Related trials for Insomnia Comorbid to Psychiatric Disorder
Recruiting
Wearable Voice-Guided BBTi for Comorbid Insomnia and Sleep Apnea (COMISA)
Comorbid Insomnia and Sleep Apnea, Insomnia
Not yet recruiting
Does the Timing of Insomnia Therapy (CBT-i) Impact the Usage and Compliance of Upper Airway Stimulation (UAS) Treatment of Obstructive Sleep Apnea (OSA)
Obstructive Sleep Apnea, Comorbid Insomnia and Sleep Apnea
Not yet recruiting
Effective of Early Treatment of Insomnia on the Adherence of CPAP
Obstructive Sleep Apnea (OSA), Insomnia Chronic
Recruiting
Brief Interventions to Reduce Comorbid Alcohol and Cannabis Misuse and Sleep Impairment in Young Adults (Rest-Up RCT)
Insomnia, Alcohol Use
RecruitingPhase 2
Resilience Enhancement Following Sleep Treatment
Chronic Low Back Pain (CLBP), Insomnia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack Edinger, PhD principal investigator
National Jewish Health
Charles Morin, PhD principal investigator
Universite Laval
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Behavioral Insomnia Therapy, Zolpidem and Trazodone in people with Insomnia Comorbid to Psychiatric Disorder and Primary Insomnia, run by Jack Edinger, PhD at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Participants Who Met Remission as Measured by the Insomnia Severity Index (time frame: 6 weeks, 12 weeks, 3 months, 6 months, 9 months & 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01651442, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2021.