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

Chronic Insomnia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04024787
• Other study ID #: 30011416
• Status: Recruiting
• Phase: N/A
• Start date: July 30, 2019
• Est. completion date: July 30, 2025

Study information

• Verified date: February 2024
• Source: Concordia University, Montreal
• Contact: Thanh Dang-Vu, MD PhD
• Phone: 514-848-2424
• Email: tt.dangvu[@]concordia.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 30, 2025
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Insomnia
• Sleep Initiation and Maintenance Disorders

Intervention

Behavioral:
• Cognitive-Behavioural therapy for insomnia (CBT-I)
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.

Locations

Country	Name	City	State
Canada	Perform Center, Concordia University	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Concordia University, Montreal	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional magnetic resonance imaging (fMRI) to examine brain responses to working memory with increasing task difficulty	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.	3 months
Primary	Functional magnetic resonance imaging (fMRI) to examine brain responses to declarative memory encoding	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.	3 months
Primary	Functional magnetic resonance imaging (fMRI) to examine brain responses to insomnia-related stimuli	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.	3 months
Primary	Functional magnetic resonance imaging (fMRI) to examine functional connectivity within the default-mode and limbic networks at rest	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.	3 months
Secondary	Insomnia Severity Index (ISI)	Self-reported insomnia severity	3 months and 1 year
Secondary	Pittsburgh Sleep Quality Index (PSQI)	Self-reported sleep quality	3 months and 1 year
Secondary	Total sleep time	Self-reported total sleep time from 14-day sleep diary	3 months and 1 year
Secondary	Total sleep time	Total sleep time from 14-day actigraphy	3 months
Secondary	Sleep latency	Self-reported sleep latency from 14-day sleep diary	3 months and 1 year
Secondary	Sleep latency	Sleep latency from 14-day actigraphy	3 months
Secondary	Wake-after-sleep-onset (WASO)	Self-reported duration of wake-after-sleep-onset from 14-day sleep diary	3 months and 1 year
Secondary	Wake-after-sleep-onset (WASO)	Duration of wake-after-sleep-onset from 14-day actigraphy	3 months
Secondary	Sleep efficiency	Self-reported sleep efficiency from 14-day sleep diary	3 months and 1 year
Secondary	Sleep efficiency	Sleep efficiency from 14-day actigraphy	3 months
Secondary	Diagnosis of insomnia disorder	A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V	3 months and 1 year
Secondary	PSG total sleep time	Total sleep time from overnight polysomnography	3 months
Secondary	PSG sleep latency	Sleep latency from overnight polysomnography	3 months
Secondary	PSG wake-after-sleep-onset (WASO)	Duration of wake-after-sleep-onset from overnight polysomnography	3 months
Secondary	PSG sleep efficiency	Sleep efficiency from overnight polysomnography	3 months
Secondary	Sleep stage durations (N1, N2, N3, REM)	Durations of each sleep stage from overnight polysomnography	3 months
Secondary	Arousal index	Number of EEG arousals per hour from overnight polysomnography	3 months
Secondary	Spindle density	Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography	3 months
Secondary	Dim light melatonin onset (DLMO)	Objective measure of central circadian timing (dim light melatonin onset; DLMO) will be obtained from hourly evening saliva samples	3 months
Secondary	Cortisol	Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening	3 months
Secondary	Heart rate variability	Heart rate variability will be measured using the electrocardiogram leads during the overnight assessments	3 months
Secondary	Blood pressure	Blood pressure is assessed using an oscillometer measurement of systolic and diastolic blood pressure in the morning following the overnight assessments	3 months
Secondary	Circulating interleukin-6	Markers will be quantified using blood sample during the overnight assessments	3 months
Secondary	Circulating tumor necrosis factor-alpha	Markers will be quantified using blood sample during the overnight assessments	3 months
Secondary	Circulating C-reactive protein	Markers will be quantified using blood sample during the overnight assessments	3 months
Secondary	Circulating neurotrophic factor BDNF	Markers will be quantified using blood sample during the overnight assessments	3 months
Secondary	Beck Depression Inventory (BDI)		3 months and 1 year
Secondary	State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA)		3 months and 1 year
Secondary	Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q, adapted version)	Questionnaire assessing self-reported (subjective) memory complaints. Total score ranges from 29 to 203 (higher score reflects more self-reported cognitive complaints).	3 months and 1 year
Secondary	Work and Social Adjustment Scale (WSAS)	Self-reported measure assessing perceived functional impairment associated with insomnia. Total score ranges from 0 to 40 (lower score reflects less impairment).	3 months and 1 year
Secondary	The Implicit Positive and Negative Affect Test (IPANAT)		3 months and 1 year
Secondary	Beliefs and Attitudes about Sleep (DBAS)		3 months and 1 year
Secondary	Daytime Insomnia Symptom Response Scale (DISRS)	Self-report measures assessing sleep-related rumination	3 months and 1 year
Secondary	Attention	Attention will be assessed using computerized divided attention and multitasking tasks assessed in the evening and morning of the overnight assessments	3 months
Secondary	Gray matter volume (GMV)	Brain morphometric measure from MRI	3 months
Secondary	Cortical thickness	Brain morphometric measure from MRI	3 months
Secondary	White matter integrity (fractional anisotropy, mean diffusivity)	Brain measure from MRI	3 months
Secondary	GABA	GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex)	3 months
Secondary	Trier Inventory for Chronic Stress - short form		3 months and 1 year
Secondary	Subjective happiness scale	Self-reported measure of global subjective happiness. Total score ranges from 4 to 28 (higher score reflects greater happiness).	3 months and 1 year
Secondary	Temporal experience of pleasure scale (adapted version)	Self-reported measure of anticipatory and consummatory facets of pleasure. Total score ranges from 18 to 52 (higher score reflects greater pleasure).	3 months and 1 year
Secondary	Fatigue symptom inventory		3 months and 1 year
Secondary	Positive and Negative Affect Schedule		3 months and 1 year
Secondary	Munich Chronotype Questionnaire (MCTQ)	Questionnaire on self-reported sleep habits, assessing individual chronotype (e.g., early type, normal type late type).	3 months and 1 year