Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks

Not Applicable

Recruiting

• Conditions: Chronic Insomnia
• Interventions: Behavioral: Cognitive-Behavioural therapy for insomnia (CBT-I)

• Registration Number: NCT04024787
• Lead Sponsor: Concordia University, Montreal

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.

Study Timeline

• Study First Submitted: 2019-07-12
• Study First Submitted QC: 2019-07-17
• Study First Posted: 2019-07-18
• Study Start: 2019-07-30
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Primary Completion: 2025-03-30
• Study Completion: 2025-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immediate intervention	Cognitive-Behavioural therapy for insomnia (CBT-I)	-

Primary Outcome Measures

Name	Time	Method
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.
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 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 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.

Secondary Outcome Measures

Name	Time	Method
PSG total sleep time	3 months	Total sleep time 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
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).
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).
Trier Inventory for Chronic Stress - short form	3 months and 1 year
PSG wake-after-sleep-onset (WASO)	3 months	Duration of wake-after-sleep-onset from overnight polysomnography
Insomnia Severity Index (ISI)	3 months and 1 year	Self-reported insomnia severity
Pittsburgh Sleep Quality Index (PSQI)	3 months and 1 year	Self-reported sleep quality
Sleep latency	3 months	Sleep latency from 14-day actigraphy
Wake-after-sleep-onset (WASO)	3 months	Duration of wake-after-sleep-onset from 14-day actigraphy
PSG sleep efficiency	3 months	Sleep efficiency from overnight polysomnography
Spindle density	3 months	Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography
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
Daytime Insomnia Symptom Response Scale (DISRS)	3 months and 1 year	Self-report measures assessing sleep-related rumination
Sleep efficiency	3 months	Sleep efficiency from 14-day actigraphy
PSG sleep latency	3 months	Sleep latency from overnight polysomnography
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
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).
Attention	3 months	Attention will be assessed using computerized divided attention and multitasking tasks assessed in the evening and morning of the overnight assessments
GABA	3 months	GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex)
Positive and Negative Affect Schedule	3 months and 1 year
Total sleep time	3 months	Total sleep time from 14-day actigraphy
Diagnosis of insomnia disorder	3 months and 1 year	A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V
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
Beck Depression Inventory (BDI)	3 months and 1 year
Beliefs and Attitudes about Sleep (DBAS)	3 months and 1 year
Cortical thickness	3 months	Brain morphometric measure from MRI
Cortisol	3 months	Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening
Gray matter volume (GMV)	3 months	Brain morphometric measure from MRI
White matter integrity (fractional anisotropy, mean diffusivity)	3 months	Brain measure from MRI
The Implicit Positive and Negative Affect Test (IPANAT)	3 months and 1 year
Fatigue symptom inventory	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).

Trial Locations

Locations (1)

Perform Center, Concordia University; 🇨🇦 Montréal, Quebec, Canada