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出境医 / 临床实验 / Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks
Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Insomnia | Behavioral: Cognitive-Behavioural therapy for insomnia (CBT-I) | Not Applicable |
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 Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 120 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| 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. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | July 30, 2019 |
| Estimated Primary Completion Date : | July 30, 2021 |
| Estimated Study Completion Date : | July 30, 2022 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
| Experimental: Immediate 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. |
| No Intervention: Waitlist |
Outcome Measures
Primary Outcome Measures :
- Functional magnetic resonance imaging (fMRI) to examine brain responses to working memory with increasing task difficulty [ Time Frame: 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 declarative memory encoding [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 :
- Insomnia Severity Index (ISI) [ Time Frame: 3 months and 1 year ]Self-reported insomnia severity
- Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 3 months and 1 year ]Self-reported sleep quality
- Total sleep time [ Time Frame: 3 months and 1 year ]Self-reported total sleep time from 14-day sleep diary
- Total sleep time [ Time Frame: 3 months ]Total sleep time from 14-day actigraphy
- Sleep latency [ Time Frame: 3 months and 1 year ]Self-reported sleep latency from 14-day sleep diary
- Sleep latency [ Time Frame: 3 months ]Sleep latency from 14-day actigraphy
- Wake-after-sleep-onset (WASO) [ Time Frame: 3 months and 1 year ]Self-reported duration of wake-after-sleep-onset from 14-day sleep diary
- Wake-after-sleep-onset (WASO) [ Time Frame: 3 months ]Duration of wake-after-sleep-onset from 14-day actigraphy
- Sleep efficiency [ Time Frame: 3 months and 1 year ]Self-reported sleep efficiency from 14-day sleep diary
- Sleep efficiency [ Time Frame: 3 months ]Sleep efficiency from 14-day actigraphy
- Diagnosis of insomnia disorder [ Time Frame: 3 months and 1 year ]A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V
- PSG total sleep time [ Time Frame: 3 months ]Total sleep time from overnight polysomnography
- PSG sleep latency [ Time Frame: 3 months ]Sleep latency from overnight polysomnography
- PSG wake-after-sleep-onset (WASO) [ Time Frame: 3 months ]Duration of wake-after-sleep-onset from overnight polysomnography
- PSG sleep efficiency [ Time Frame: 3 months ]Sleep efficiency from overnight polysomnography
- Sleep stage durations (N1, N2, N3, REM) [ Time Frame: 3 months ]Durations of each sleep stage from overnight polysomnography
- Arousal index [ Time Frame: 3 months ]Number of EEG arousals per hour from overnight polysomnography
- Spindle density [ Time Frame: 3 months ]Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography
- Dim light melatonin onset (DLMO) [ Time Frame: 3 months ]Objective measure of central circadian timing (dim light melatonin onset; DLMO) will be obtained from hourly evening saliva samples
- Cortisol [ Time Frame: 3 months ]Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening
- Heart rate variability [ Time Frame: 3 months ]Heart rate variability will be measured using the electrocardiogram leads during the overnight assessments
- Blood pressure [ Time Frame: 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 [ Time Frame: 3 months ]Markers will be quantified using blood sample during the overnight assessments
- Circulating tumor necrosis factor-alpha [ Time Frame: 3 months ]Markers will be quantified using blood sample during the overnight assessments
- Circulating C-reactive protein [ Time Frame: 3 months ]Markers will be quantified using blood sample during the overnight assessments
- Circulating neurotrophic factor BDNF [ Time Frame: 3 months ]Markers will be quantified using blood sample during the overnight assessments
- Beck Depression Inventory (BDI) [ Time Frame: 3 months and 1 year ]
- State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) [ Time Frame: 3 months and 1 year ]
- Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q, adapted version) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 3 months and 1 year ]
- Beliefs and Attitudes about Sleep (DBAS) [ Time Frame: 3 months and 1 year ]
- Daytime Insomnia Symptom Response Scale (DISRS) [ Time Frame: 3 months and 1 year ]Self-report measures assessing sleep-related rumination
- Attention [ Time Frame: 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) [ Time Frame: 3 months ]Brain morphometric measure from MRI
- Cortical thickness [ Time Frame: 3 months ]Brain morphometric measure from MRI
- White matter integrity (fractional anisotropy, mean diffusivity) [ Time Frame: 3 months ]Brain measure from MRI
- GABA [ Time Frame: 3 months ]GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex)
- Trier Inventory for Chronic Stress - short form [ Time Frame: 3 months and 1 year ]
- Subjective happiness scale [ Time Frame: 3 months and 1 year ]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) [ Time Frame: 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 [ Time Frame: 3 months and 1 year ]
- Positive and Negative Affect Schedule [ Time Frame: 3 months and 1 year ]
- Munich Chronotype Questionnaire (MCTQ) [ Time Frame: 3 months and 1 year ]Questionnaire on self-reported sleep habits, assessing individual chronotype (e.g., early type, normal type late type).
Eligibility Criteria
| Ages Eligible for Study: | 25 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations
Contacts
| Contact: Thanh Dang-Vu, MD PhD | 514-848-2424 ext 3364 | tt.dangvu@concordia.ca |
Locations
| Canada, Quebec | |
| Perform Center, Concordia University | Recruiting |
| Montréal, Quebec, Canada, H4B 1R6 | |
| Contact: Thanh Dang-Vu, MD PhD | |
Sponsors and Collaborators
Concordia University, Montreal
Canadian Institutes of Health Research (CIHR)
Investigators
| Principal Investigator: | Thanh Dang-Vu, MD PhD | Concordia University, Montreal |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | July 12, 2019 | ||||
| First Posted Date ICMJE | July 18, 2019 | ||||
| Last Update Posted Date | January 27, 2021 | ||||
| Actual Study Start Date ICMJE | July 30, 2019 | ||||
| Estimated Primary Completion Date | July 30, 2021 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks | ||||
| Official Title ICMJE | 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 | ||||
| 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. |
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| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Not Applicable | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment 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. Masking: None (Open Label)Primary Purpose: Treatment |
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| Condition ICMJE | Chronic Insomnia | ||||
| Intervention ICMJE | 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. |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
120 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | July 30, 2022 | ||||
| Estimated Primary Completion Date | July 30, 2021 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria: 80 participants with chronic primary insomnia (40 per group) 40 good sleepers Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 25 Years to 65 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | Yes | ||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | Canada | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT04024787 | ||||
| Other Study ID Numbers ICMJE | 30011416 | ||||
| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Thanh Dang-Vu, Concordia University, Montreal | ||||
| Study Sponsor ICMJE | Concordia University, Montreal | ||||
| Collaborators ICMJE | Canadian Institutes of Health Research (CIHR) | ||||
| Investigators ICMJE |
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| PRS Account | Concordia University, Montreal | ||||
| Verification Date | January 2021 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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