Back to resultsImpact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks
Primary Purpose
Chronic Insomnia
Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Cognitive-Behavioural therapy for insomnia (CBT-I)
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Insomnia
Eligibility Criteria
Inclusion Criteria:
80 participants with chronic primary insomnia (40 per group) 40 good sleepers
Exclusion Criteria:
- Older than 65 y.o. or younger than 25 y.o.
- Contraindication to the MRI scanning
- Current neurological disorder
- Past history of brain lesion
- Major surgery (i.e., requiring general anesthesia) in the past 3 months
- Untreated thyroid disorder
- Chronic pain syndrome self-reported as interfering with sleep
- Recent and severe infection in the past 3 months
- Active cancer, or remitted cancer with cancer treatment within the last 2 years
- Stroke
- Myocardial infarct
- Arterial bypass or angioplasty
- Pacemaker
- Heart failure causing limitation of ordinary physical activity
- Renal insufficiency
- Sleep apnea with an apnea-hypopnea index > 5/h
- Restless legs syndrome with symptoms 3 days or more per week
- Periodic limb movements during sleep with index > 15/h
- REM-sleep behavior disorder
- Narcolepsy and other central disorders of hypersomnolence
- Sleepwalking more than once/month
- 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
- Severe mental disorders: bipolar disorder (Type I), schizophrenia, anxiety disorders, major depressive disorder, current substance use disorder, current post-traumatic stress disorder
- Current suicidality
- Frequent alcohol consumption (>10 glasses/week) or use of cannabis (more than once a week) or illicit drugs (more than once a month)
- Smoking cigarettes more than 10 cigarettes/day
- Pregnant or breastfeeding women
- Current psychotherapy or past cognitive-behavioural therapy for insomnia
- Current use of medication for depression or anxiety
- Unable to stop hypnosedative medications for at least 2 weeks prior to the first assessment
- For good sleepers: insomnia symptoms more than 3 times/ week.
Sites / Locations
- Perform Center, Concordia UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Immediate intervention
Waitlist
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
Insomnia Severity Index (ISI)
Self-reported insomnia severity
Pittsburgh Sleep Quality Index (PSQI)
Self-reported sleep quality
Total sleep time
Self-reported total sleep time from 14-day sleep diary
Total sleep time
Total sleep time from 14-day actigraphy
Sleep latency
Self-reported sleep latency from 14-day sleep diary
Sleep latency
Sleep latency from 14-day actigraphy
Wake-after-sleep-onset (WASO)
Self-reported duration of wake-after-sleep-onset from 14-day sleep diary
Wake-after-sleep-onset (WASO)
Duration of wake-after-sleep-onset from 14-day actigraphy
Sleep efficiency
Self-reported sleep efficiency from 14-day sleep diary
Sleep efficiency
Sleep efficiency from 14-day actigraphy
Diagnosis of insomnia disorder
A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V
PSG total sleep time
Total sleep time from overnight polysomnography
PSG sleep latency
Sleep latency from overnight polysomnography
PSG wake-after-sleep-onset (WASO)
Duration of wake-after-sleep-onset from overnight polysomnography
PSG sleep efficiency
Sleep efficiency from overnight polysomnography
Sleep stage durations (N1, N2, N3, REM)
Durations of each sleep stage from overnight polysomnography
Arousal index
Number of EEG arousals per hour from overnight polysomnography
Spindle density
Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography
Dim light melatonin onset (DLMO)
Objective measure of central circadian timing (dim light melatonin onset; DLMO) will be obtained from hourly evening saliva samples
Cortisol
Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening
Heart rate variability
Heart rate variability will be measured using the electrocardiogram leads during the overnight assessments
Blood pressure
Blood pressure is assessed using an oscillometer measurement of systolic and diastolic blood pressure in the morning following the overnight assessments
Circulating interleukin-6
Markers will be quantified using blood sample during the overnight assessments
Circulating tumor necrosis factor-alpha
Markers will be quantified using blood sample during the overnight assessments
Circulating C-reactive protein
Markers will be quantified using blood sample during the overnight assessments
Circulating neurotrophic factor BDNF
Markers will be quantified using blood sample during the overnight assessments
Beck Depression Inventory (BDI)
State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA)
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).
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).
The Implicit Positive and Negative Affect Test (IPANAT)
Beliefs and Attitudes about Sleep (DBAS)
Daytime Insomnia Symptom Response Scale (DISRS)
Self-report measures assessing sleep-related rumination
Attention
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)
Brain morphometric measure from MRI
Cortical thickness
Brain morphometric measure from MRI
White matter integrity (fractional anisotropy, mean diffusivity)
Brain measure from MRI
GABA
GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex)
Trier Inventory for Chronic Stress - short form
Subjective happiness scale
Self-reported measure of global subjective happiness. Total score ranges from 4 to 28 (higher score reflects greater happiness).
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).
Fatigue symptom inventory
Positive and Negative Affect Schedule
Munich Chronotype Questionnaire (MCTQ)
Questionnaire on self-reported sleep habits, assessing individual chronotype (e.g., early type, normal type late type).
Full Information
NCT ID
NCT04024787
First Posted
July 12, 2019
Last Updated
March 7, 2022
Sponsor
Concordia University, Montreal
Collaborators
Canadian Institutes of Health Research (CIHR)
1. Study Identification
Unique Protocol Identification Number
NCT04024787
Brief Title
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
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 30, 2019 (Actual)
Primary Completion Date
July 30, 2023 (Anticipated)
Study Completion Date
July 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Concordia University, Montreal
Collaborators
Canadian Institutes of Health Research (CIHR)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Insomnia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Immediate intervention
Arm Type
Experimental
Arm Title
Waitlist
Arm Type
No Intervention
Intervention Type
Behavioral
Intervention Name(s)
Cognitive-Behavioural therapy for insomnia (CBT-I)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Functional magnetic resonance imaging (fMRI) to examine brain responses to working memory with increasing task difficulty
Description
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.
Time Frame
3 months
Title
Functional magnetic resonance imaging (fMRI) to examine brain responses to declarative memory encoding
Description
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.
Time Frame
3 months
Title
Functional magnetic resonance imaging (fMRI) to examine brain responses to insomnia-related stimuli
Description
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.
Time Frame
3 months
Title
Functional magnetic resonance imaging (fMRI) to examine functional connectivity within the default-mode and limbic networks at rest
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Insomnia Severity Index (ISI)
Description
Self-reported insomnia severity
Time Frame
3 months and 1 year
Title
Pittsburgh Sleep Quality Index (PSQI)
Description
Self-reported sleep quality
Time Frame
3 months and 1 year
Title
Total sleep time
Description
Self-reported total sleep time from 14-day sleep diary
Time Frame
3 months and 1 year
Title
Total sleep time
Description
Total sleep time from 14-day actigraphy
Time Frame
3 months
Title
Sleep latency
Description
Self-reported sleep latency from 14-day sleep diary
Time Frame
3 months and 1 year
Title
Sleep latency
Description
Sleep latency from 14-day actigraphy
Time Frame
3 months
Title
Wake-after-sleep-onset (WASO)
Description
Self-reported duration of wake-after-sleep-onset from 14-day sleep diary
Time Frame
3 months and 1 year
Title
Wake-after-sleep-onset (WASO)
Description
Duration of wake-after-sleep-onset from 14-day actigraphy
Time Frame
3 months
Title
Sleep efficiency
Description
Self-reported sleep efficiency from 14-day sleep diary
Time Frame
3 months and 1 year
Title
Sleep efficiency
Description
Sleep efficiency from 14-day actigraphy
Time Frame
3 months
Title
Diagnosis of insomnia disorder
Description
A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V
Time Frame
3 months and 1 year
Title
PSG total sleep time
Description
Total sleep time from overnight polysomnography
Time Frame
3 months
Title
PSG sleep latency
Description
Sleep latency from overnight polysomnography
Time Frame
3 months
Title
PSG wake-after-sleep-onset (WASO)
Description
Duration of wake-after-sleep-onset from overnight polysomnography
Time Frame
3 months
Title
PSG sleep efficiency
Description
Sleep efficiency from overnight polysomnography
Time Frame
3 months
Title
Sleep stage durations (N1, N2, N3, REM)
Description
Durations of each sleep stage from overnight polysomnography
Time Frame
3 months
Title
Arousal index
Description
Number of EEG arousals per hour from overnight polysomnography
Time Frame
3 months
Title
Spindle density
Description
Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography
Time Frame
3 months
Title
Dim light melatonin onset (DLMO)
Description
Objective measure of central circadian timing (dim light melatonin onset; DLMO) will be obtained from hourly evening saliva samples
Time Frame
3 months
Title
Cortisol
Description
Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening
Time Frame
3 months
Title
Heart rate variability
Description
Heart rate variability will be measured using the electrocardiogram leads during the overnight assessments
Time Frame
3 months
Title
Blood pressure
Description
Blood pressure is assessed using an oscillometer measurement of systolic and diastolic blood pressure in the morning following the overnight assessments
Time Frame
3 months
Title
Circulating interleukin-6
Description
Markers will be quantified using blood sample during the overnight assessments
Time Frame
3 months
Title
Circulating tumor necrosis factor-alpha
Description
Markers will be quantified using blood sample during the overnight assessments
Time Frame
3 months
Title
Circulating C-reactive protein
Description
Markers will be quantified using blood sample during the overnight assessments
Time Frame
3 months
Title
Circulating neurotrophic factor BDNF
Description
Markers will be quantified using blood sample during the overnight assessments
Time Frame
3 months
Title
Beck Depression Inventory (BDI)
Time Frame
3 months and 1 year
Title
State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA)
Time Frame
3 months and 1 year
Title
Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q, adapted version)
Description
Questionnaire assessing self-reported (subjective) memory complaints. Total score ranges from 29 to 203 (higher score reflects more self-reported cognitive complaints).
Time Frame
3 months and 1 year
Title
Work and Social Adjustment Scale (WSAS)
Description
Self-reported measure assessing perceived functional impairment associated with insomnia. Total score ranges from 0 to 40 (lower score reflects less impairment).
Time Frame
3 months and 1 year
Title
The Implicit Positive and Negative Affect Test (IPANAT)
Time Frame
3 months and 1 year
Title
Beliefs and Attitudes about Sleep (DBAS)
Time Frame
3 months and 1 year
Title
Daytime Insomnia Symptom Response Scale (DISRS)
Description
Self-report measures assessing sleep-related rumination
Time Frame
3 months and 1 year
Title
Attention
Description
Attention will be assessed using computerized divided attention and multitasking tasks assessed in the evening and morning of the overnight assessments
Time Frame
3 months
Title
Gray matter volume (GMV)
Description
Brain morphometric measure from MRI
Time Frame
3 months
Title
Cortical thickness
Description
Brain morphometric measure from MRI
Time Frame
3 months
Title
White matter integrity (fractional anisotropy, mean diffusivity)
Description
Brain measure from MRI
Time Frame
3 months
Title
GABA
Description
GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex)
Time Frame
3 months
Title
Trier Inventory for Chronic Stress - short form
Time Frame
3 months and 1 year
Title
Subjective happiness scale
Description
Self-reported measure of global subjective happiness. Total score ranges from 4 to 28 (higher score reflects greater happiness).
Time Frame
3 months and 1 year
Title
Temporal experience of pleasure scale (adapted version)
Description
Self-reported measure of anticipatory and consummatory facets of pleasure. Total score ranges from 18 to 52 (higher score reflects greater pleasure).
Time Frame
3 months and 1 year
Title
Fatigue symptom inventory
Time Frame
3 months and 1 year
Title
Positive and Negative Affect Schedule
Time Frame
3 months and 1 year
Title
Munich Chronotype Questionnaire (MCTQ)
Description
Questionnaire on self-reported sleep habits, assessing individual chronotype (e.g., early type, normal type late type).
Time Frame
3 months and 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
80 participants with chronic primary insomnia (40 per group) 40 good sleepers
Exclusion Criteria:
Older than 65 y.o. or younger than 25 y.o.
Contraindication to the MRI scanning
Current neurological disorder
Past history of brain lesion
Major surgery (i.e., requiring general anesthesia) in the past 3 months
Untreated thyroid disorder
Chronic pain syndrome self-reported as interfering with sleep
Recent and severe infection in the past 3 months
Active cancer, or remitted cancer with cancer treatment within the last 2 years
Stroke
Myocardial infarct
Arterial bypass or angioplasty
Pacemaker
Heart failure causing limitation of ordinary physical activity
Renal insufficiency
Sleep apnea with an apnea-hypopnea index > 5/h
Restless legs syndrome with symptoms 3 days or more per week
Periodic limb movements during sleep with index > 15/h
REM-sleep behavior disorder
Narcolepsy and other central disorders of hypersomnolence
Sleepwalking more than once/month
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
Severe mental disorders: bipolar disorder (Type I), schizophrenia, anxiety disorders, major depressive disorder, current substance use disorder, current post-traumatic stress disorder
Current suicidality
Frequent alcohol consumption (>10 glasses/week) or use of cannabis (more than once a week) or illicit drugs (more than once a month)
Smoking cigarettes more than 10 cigarettes/day
Pregnant or breastfeeding women
Current psychotherapy or past cognitive-behavioural therapy for insomnia
Current use of medication for depression or anxiety
Unable to stop hypnosedative medications for at least 2 weeks prior to the first assessment
For good sleepers: insomnia symptoms more than 3 times/ week.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thanh Dang-Vu, MD PhD
Phone
514-848-2424
Ext
3364
Email
tt.dangvu@concordia.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thanh Dang-Vu, MD PhD
Organizational Affiliation
Concordia University, Montreal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Perform Center, Concordia University
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4B 1R6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thanh Dang-Vu, MD PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks
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