Chronic Insomnia
Conditions
Brief summary
Individuals with chronic insomnia have persistent difficulty falling and staying asleep, as well as complaints of altered daytime functioning that may be associated with cognitive impairments. The neural processes underlying these daytime complaints may involve abnormal activation of brain regions and neural networks involved in working memory, memory encoding and emotions. The goal of this study is to assess whether a psychological treatment for insomnia will reverse these abnormalities in brain responses to cognitive tasks and at rest. A secondary objective of the study is to characterize impairments in attentional processing and assess if the impairments can be reversed by the psychological treatment. We hypothesized that the psychological treatment for insomnia will lead to a normalization of the brain responses to working memory, declarative memory encoding, insomnia-related stimuli, and the functional connectivity within the default-mode and limbic networks.
Detailed description
Study hypothesis Brain responses associated with working memory task and declarative memory encoding will be decreased in chronic insomnia compared to good sleepers and, among individuals with chronic insomnia, cognitive-behavioral therapy for insomnia will lead to larger recovery in these brain responses, compared to a 3-month wait period. Brain responses to emotional stimulation, especially to insomnia-related stimuli, will be increased in chronic insomnia compared to good sleepers, and, among individuals with chronic insomnia, cognitive-behavioral therapy for insomnia will lead to larger reduction in these brain responses, compared to a 3-month wait period. Connectivity in the default-mode and limbic networks during resting-state will be increased in chronic insomnia compared to good sleepers, and, among individuals with chronic insomnia, cognitive-behavioral therapy for insomnia will lead to larger reduction in this connectivity, compared to a 3-month wait period.
Interventions
Participants with chronic primary insomnia are randomized into 2 groups with a 1:1 allocation ratio, after the completion of the pre-treatment assessment. Post-treatment and post-waitlist assessment occur after the 3-month treatment or waiting period. One group will receive the intervention immediately after the pre-treatment assessment and the other group will receive the intervention after a waiting period of 3 months. The intervention consists of manualized cognitive-behavioural therapy for insomnia. This treatment includes psychoeducation about sleep and circadian rhythms, stimulus control, sleep restriction, relaxation, and cognitive therapy. The therapy is administered individually. Participants meet for 8 sessions of 50 minutes spread over 12 weeks.
Sponsors
Concordia University, Montreal
Canadian Institutes of Health Research (CIHR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is a randomized controlled trial. Participants with chronic insomnia are randomized to either immediate cognitive-behavioural therapy or a 3-month wait-list period using a 1:1 allocation ratio. Randomization is conducted with block sizes of 4 participants. Randomization results are contained in sealed opaque envelopes that are opened in the presence of the participants after the completion of the pre-treatment assessment. A second assessment will be conducted after the treatment or waiting period. A follow-up assessment is conducted 12 months after the completion of the post-treatment assessment. A group of good sleepers, matched on age and gender with the insomniacs, will also be recruited and assessed at baseline only to provide a normative reference group.
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
80 participants with chronic primary insomnia (40 per group) 40 good sleepers
Exclusion criteria
1. Older than 65 y.o. or younger than 25 y.o. 2. Contraindication to the MRI scanning 3. Current neurological disorder 4. Past history of brain lesion 5. Major surgery (i.e., requiring general anesthesia) in the past 3 months 6. Untreated thyroid disorder 7. Chronic pain syndrome self-reported as interfering with sleep 8. Recent and severe infection in the past 3 months 9. Active cancer, or remitted cancer with cancer treatment within the last 2 years 10. Stroke 11. Myocardial infarct 12. Arterial bypass or angioplasty 13. Pacemaker 14. Heart failure causing limitation of ordinary physical activity 15. Renal insufficiency 16. Sleep apnea with an apnea-hypopnea index \> 5/h 17. Restless legs syndrome with symptoms 3 days or more per week 18. Periodic limb movements during sleep with index \> 15/h 19. REM-sleep behavior disorder 20. Narcolepsy and other central disorders of hypersomnolence 21. Sleepwalking more than once/month 22. Having worked on night shifts or rotating shifts for more than 2 weeks in the last 3 months or expecting to do so during the study period 23. Severe mental disorders: bipolar disorder (Type I), schizophrenia, anxiety disorders, major depressive disorder, current substance use disorder, current post-traumatic stress disorder 24. Current suicidality 25. Frequent alcohol consumption (\>10 glasses/week) or use of cannabis (more than once a week) or illicit drugs (more than once a month) 26. Smoking cigarettes more than 10 cigarettes/day 27. Pregnant or breastfeeding women 28. Current psychotherapy or past cognitive-behavioural therapy for insomnia 29. Current use of medication for depression or anxiety 30. Unable to stop hypnosedative medications for at least 2 weeks prior to the first assessment 31. For good sleepers: insomnia symptoms more than 3 times/ week.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional magnetic resonance imaging (fMRI) to examine brain responses to declarative memory encoding | 3 months | Functional magnetic resonance imaging (fMRI) will be used to look at changes in brain activations to declarative memory encoding in individuals with chronic insomnia compared to good sleepers, as well as the modifications in these brain activations after cognitive-behavioral therapy for insomnia. |
| Functional magnetic resonance imaging (fMRI) to examine brain responses to insomnia-related stimuli | 3 months | Functional magnetic resonance imaging (fMRI) will be used to look at changes in brain activations to insomnia-related pictures in individuals with chronic insomnia compared to good sleepers, as well as the modifications in these brain activations after cognitive-behavioral therapy for insomnia. |
| Functional magnetic resonance imaging (fMRI) to examine functional connectivity within the default-mode and limbic networks at rest | 3 months | Functional magnetic resonance imaging (fMRI) will be used to look at changes in resting state functional connectivity in individuals with chronic insomnia compared to good sleepers, as well as the modifications in this functional connectivity after cognitive-behavioral therapy for insomnia, with a focus on the default-mode and limbic networks. |
| Functional magnetic resonance imaging (fMRI) to examine brain responses to working memory with increasing task difficulty | 3 months | Functional magnetic resonance imaging (fMRI) will be used to look at changes in brain activations to working memory in individuals with chronic insomnia compared to good sleepers, as well as the modifications in these brain activations after cognitive-behavioral therapy for insomnia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pittsburgh Sleep Quality Index (PSQI) | 3 months and 1 year | Self-reported sleep quality |
| Total sleep time | 3 months and 1 year | Self-reported total sleep time from 14-day sleep diary |
| Sleep latency | 3 months and 1 year | Self-reported sleep latency from 14-day sleep diary |
| Wake-after-sleep-onset (WASO) | 3 months and 1 year | Self-reported duration of wake-after-sleep-onset from 14-day sleep diary |
| Sleep efficiency | 3 months and 1 year | Self-reported sleep efficiency from 14-day sleep diary |
| Diagnosis of insomnia disorder | 3 months and 1 year | A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V |
| PSG total sleep time | 3 months | Total sleep time from overnight polysomnography |
| PSG sleep latency | 3 months | Sleep latency from overnight polysomnography |
| PSG wake-after-sleep-onset (WASO) | 3 months | Duration of wake-after-sleep-onset from overnight polysomnography |
| PSG sleep efficiency | 3 months | Sleep efficiency from overnight polysomnography |
| Sleep stage durations (N1, N2, N3, REM) | 3 months | Durations of each sleep stage from overnight polysomnography |
| Arousal index | 3 months | Number of EEG arousals per hour from overnight polysomnography |
| Spindle density | 3 months | Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography |
| Dim light melatonin onset (DLMO) | 3 months | Objective measure of central circadian timing (dim light melatonin onset; DLMO) will be obtained from hourly evening saliva samples |
| Cortisol | 3 months | Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening |
| Heart rate variability | 3 months | Heart rate variability will be measured using the electrocardiogram leads during the overnight assessments |
| Blood pressure | 3 months | Blood pressure is assessed using an oscillometer measurement of systolic and diastolic blood pressure in the morning following the overnight assessments |
| Circulating interleukin-6 | 3 months | Markers will be quantified using blood sample during the overnight assessments |
| Circulating tumor necrosis factor-alpha | 3 months | Markers will be quantified using blood sample during the overnight assessments |
| Circulating C-reactive protein | 3 months | Markers will be quantified using blood sample during the overnight assessments |
| Circulating neurotrophic factor BDNF | 3 months | Markers will be quantified using blood sample during the overnight assessments |
| Beck Depression Inventory (BDI) | 3 months and 1 year | — |
| State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) | 3 months and 1 year | — |
| Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q, adapted version) | 3 months and 1 year | Questionnaire assessing self-reported (subjective) memory complaints. Total score ranges from 29 to 203 (higher score reflects more self-reported cognitive complaints). |
| Work and Social Adjustment Scale (WSAS) | 3 months and 1 year | Self-reported measure assessing perceived functional impairment associated with insomnia. Total score ranges from 0 to 40 (lower score reflects less impairment). |
| The Implicit Positive and Negative Affect Test (IPANAT) | 3 months and 1 year | — |
| Beliefs and Attitudes about Sleep (DBAS) | 3 months and 1 year | — |
| Daytime Insomnia Symptom Response Scale (DISRS) | 3 months and 1 year | Self-report measures assessing sleep-related rumination |
| Attention | 3 months | Attention will be assessed using computerized divided attention and multitasking tasks assessed in the evening and morning of the overnight assessments |
| Gray matter volume (GMV) | 3 months | Brain morphometric measure from MRI |
| Cortical thickness | 3 months | Brain morphometric measure from MRI |
| White matter integrity (fractional anisotropy, mean diffusivity) | 3 months | Brain measure from MRI |
| GABA | 3 months | GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex) |
| Trier Inventory for Chronic Stress - short form | 3 months and 1 year | — |
| Subjective happiness scale | 3 months and 1 year | Self-reported measure of global subjective happiness. Total score ranges from 4 to 28 (higher score reflects greater happiness). |
| Positive and Negative Affect Schedule | 3 months and 1 year | — |
| Munich Chronotype Questionnaire (MCTQ) | 3 months and 1 year | Questionnaire on self-reported sleep habits, assessing individual chronotype (e.g., early type, normal type late type). |
| Temporal experience of pleasure scale (adapted version) | 3 months and 1 year | Self-reported measure of anticipatory and consummatory facets of pleasure. Total score ranges from 18 to 52 (higher score reflects greater pleasure). |
| Fatigue symptom inventory | 3 months and 1 year | — |
| Insomnia Severity Index (ISI) | 3 months and 1 year | Self-reported insomnia severity |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORThanh Dang-Vu, MD PhD
Concordia University, Montreal
Outcome results
None listed