Clinical trial NCT04024787: Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks
Official title: Neural Responses and Connectivity During Rest, Memory Encoding and Emotional Stimulation in Chronic Insomnia, and Their Relationships With Insomnia Treatment: a Wait-list Controlled Randomized Trial of Cognitive-behavioural Therapy for Insomnia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Insomnia
Lead sponsor: Concordia University, Montreal
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2019-07-18
Enrollment: 120
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Functional magnetic resonance imaging (fMRI) to examine brain responses to working memory with increasing task difficulty
timeFrame: 3 months
measure: Functional magnetic resonance imaging (fMRI) to examine brain responses to declarative memory encoding
timeFrame: 3 months
measure: Functional magnetic resonance imaging (fMRI) to examine brain responses to insomnia-related stimuli
timeFrame: 3 months
measure: Functional magnetic resonance imaging (fMRI) to examine functional connectivity within the default-mode and limbic networks at rest
timeFrame: 3 months
Secondary outcomes:
measure: Insomnia Severity Index (ISI)
timeFrame: 3 months and 1 year
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 3 months and 1 year
measure: Total sleep time
timeFrame: 3 months and 1 year
measure: Total sleep time
timeFrame: 3 months
measure: Sleep latency
timeFrame: 3 months and 1 year
measure: Sleep latency
timeFrame: 3 months
measure: Wake-after-sleep-onset (WASO)
timeFrame: 3 months and 1 year
measure: Wake-after-sleep-onset (WASO)
timeFrame: 3 months
measure: Sleep efficiency
timeFrame: 3 months and 1 year
measure: Sleep efficiency
timeFrame: 3 months
measure: Diagnosis of insomnia disorder
timeFrame: 3 months and 1 year
measure: PSG total sleep time
timeFrame: 3 months
measure: PSG sleep latency
timeFrame: 3 months
measure: PSG wake-after-sleep-onset (WASO)
timeFrame: 3 months
measure: PSG sleep efficiency
timeFrame: 3 months
measure: Sleep stage durations (N1, N2, N3, REM)
timeFrame: 3 months
measure: Arousal index
timeFrame: 3 months
measure: Spindle density
timeFrame: 3 months
measure: Dim light melatonin onset (DLMO)
timeFrame: 3 months
measure: Cortisol
timeFrame: 3 months
measure: Heart rate variability
timeFrame: 3 months
measure: Blood pressure
timeFrame: 3 months
measure: Circulating interleukin-6
timeFrame: 3 months
measure: Circulating tumor necrosis factor-alpha
timeFrame: 3 months
measure: Circulating C-reactive protein
timeFrame: 3 months
measure: Circulating neurotrophic factor BDNF
timeFrame: 3 months
measure: Beck Depression Inventory (BDI)
timeFrame: 3 months and 1 year
measure: State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA)
timeFrame: 3 months and 1 year
measure: Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q, adapted version)
timeFrame: 3 months and 1 year
measure: Work and Social Adjustment Scale (WSAS)
timeFrame: 3 months and 1 year
measure: The Implicit Positive and Negative Affect Test (IPANAT)
timeFrame: 3 months and 1 year
measure: Beliefs and Attitudes about Sleep (DBAS)
timeFrame: 3 months and 1 year
measure: Daytime Insomnia Symptom Response Scale (DISRS)
timeFrame: 3 months and 1 year
measure: Attention
timeFrame: 3 months
measure: Gray matter volume (GMV)
timeFrame: 3 months
measure: Cortical thickness
timeFrame: 3 months
measure: White matter integrity (fractional anisotropy, mean diffusivity)
timeFrame: 3 months
measure: GABA
timeFrame: 3 months
measure: Trier Inventory for Chronic Stress - short form
timeFrame: 3 months and 1 year
measure: Subjective happiness scale
timeFrame: 3 months and 1 year
measure: Temporal experience of pleasure scale (adapted version)
timeFrame: 3 months and 1 year
measure: Fatigue symptom inventory
timeFrame: 3 months and 1 year
measure: Positive and Negative Affect Schedule
timeFrame: 3 months and 1 year
measure: Munich Chronotype Questionnaire (MCTQ)
timeFrame: 3 months and 1 year
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Perform Center, Concordia University
state: Quebec
Study officials:
affiliation: Concordia University, Montreal
name: Thanh Dang-Vu, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: