Clinical trial NCT06373718: Sleep Mechanisms Of Regulating Emotions
Official title: A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety (R33 Phase)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insomnia
Depression
Keywords: Insomnia
Depression
Anxiety
CBT-I
Cognitive Behavioral Therapy for Insomnia
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2024-04-18
Enrollment: 150
Sex: ALL
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Enrolled participants will be randomized into either the Immediate Treatment group, or the Enhanced Sleep Hygiene group. Both study groups will receive CBT-I.
Primary purpose: TREATMENT

Brief summary: This project is the second phase of a two-phased project investigating the impact of a proven sleep intervention, Cognitive Behavioral Therapy for Insomnia (CBT-I) on engagement of the emotion regulation brain network as a putative mechanistic target.

Detailed description: Several lines of evidence suggest that insomnia contributes to emotionally distressing depressive mood symptoms through disruption of brain networks that regulate emotional functions. Of particular concern, insomnia is associated with an increased risk for suicide, even when accounting for the presence of other depressive symptoms. However, it is not yet know to what degree that the emotion regulation brain network is modified by the restoration of sleep, or whether the degree to which a sleep intervention engages these neural targets mediates reductions in depressive symptoms and suicidality.

This project is the second phase of a two-phased project investigating the impact of a proven sleep intervention, Cognitive Behavioral Therapy for Insomnia (CBT-I) on engagement of the emotion regulation brain network as a putative mechanistic target.

This project aims to extend the initial findings from the first phase (IRB-56961) to (1) confirm target engagement, defined as the treatment effect on increasing mPFC-amygdala connectivity, and/or decreasing amygdala reactivity during emotion reactivity and regulation paradigms, by testing the hypothesis that compared with a control condition, CBT-I participants will show significant change in the emotion regulation network targets that met the Go Criteria of the first phase in the direction of normalization, at the end of treatment, (2) examine the relationships of target engagement to treatment outcomes by study group, and (3) test whether emotion regulation network measures at baseline predict depressive symptom and suicidality reduction.

Participants will be 150 adults experiencing at least moderate sleep disturbances and who also have elevated anxious and/or depressive symptoms. Eligible participants will be randomized into either the Immediate Treatment group, which will receive six sessions of CBT-I over the eight weeks of treatment phase immediately after randomization, or the Enhanced Sleep Hygiene group, which will be provided with two sessions of sleep hygiene / sleep education and four additional meetings including monitoring of sleep and mood symptoms and will be offered the same CBT-I as the Immediate Treatment group upon completion of the 6-month follow-up session, approximately 7 months after randomization. Emotion distress and sleep disruption will be assessed prior to, and weekly during the eight weeks of treatment phase. CBT-I improves sleep patterns through a combination of sleep restriction, stimulus control, mindfulness training, cognitive therapy targeting dysfunctional beliefs about sleep, and sleep hygiene education. Using fMRI scanning, emotion regulation network neural targets will be assayed prior to and following completion of CBT-I treatment.

Eligibility criteria: Inclusion Criteria:

* Males and females of any racial or ethnic group, aged 25-60
* Subjective complaint of insomnia associated with daytime impairment or distress (ISI ≥ 10)
* Insomnia complaint ≥ 3 months in duration
* Subjective complaint of depressive symptoms as defined by scores of ≥ 14 on the BDI
* Fluent and literate in English
* Written, informed consent
* Reside within 60 miles of Stanford University

Exclusion Criteria:

* Presence of other sleep or circadian rhythm disorders that significantly contribute to their sleep disturbance. The presence of these disorders will be assessed by the DUKE structured interview for sleep disorders
* Use of psychotropic medications that would significantly impact sleep, alertness, or mood and unwilling or unable to discontinue medication specifically prescribed for sleep disturbance \> two weeks (anti-depressants) or \>1 week (sleep medications) prior to baseline data collection
* Excessive alcohol consumption (\>14 drinks per week or \> 4 drinks per occasion)
* Presence of suicidal ideations representing imminent risk as determined by the empirically-supported, standardized suicide risk assessment
* General medical condition, disease or neurological disorder that interferes with the assessments
* Substance abuse or dependence
* History of significant head trauma followed by persistent neurological deficits or known structural brain abnormalities OR traumatic brain injury in the past two months
* Severe impediment to vision, hearing and/or hand movement, likely to interfere with the ability to complete the assessments, or are unable and/or unlikely to follow the study protocols
* Pregnant or breast feeding
* Current or lifetime history of bipolar disorder or psychosis
* Current or expected cognitive behavior therapy or other evidence-based psychotherapies for another condition
* Received cognitive behavioral therapy for insomnia within the past year
* Acute or unstable chronic illness: including but not limited to: uncontrolled thyroid disease, kidney, prostate or bladder conditions causing excessively frequent urination (\> 3 times per night); medically unstable congestive heart failure, angina, other severe cardiac illness as defined by treatment regimen changes in the prior 3 months; stroke with serious sequelae; cancer if \< 1 year since end of treatment; asthma, emphysema, or other severe respiratory diseases uncontrolled with medications; and neurological disorders such as Alzheimer's disease, Parkinson's disease and unstable epilepsy as defined by treatment regimen changes in the prior 3 months; unstable adult onset diabetes as defined by treatment regimen changes in the prior 3 months
* Current exposure to trauma, or exposure to trauma within the past 3 months
* Working a rotating shift that overlaps with 2400h
* Individuals who were high risk for sleep apnea on the Berlin Questionnaire and are not CPAP adherent or have untreated OSA of moderate severity or worse (AHI ≥ 15)

Primary outcomes:
measure: Change in Emotion Regulation Network brain activation as assessed by functional magnetic resonance imaging
timeFrame: Assessed at baseline (week 1) and end of treatment (week 13)
measure: Change in Emotion Regulation Network brain connectivity as assessed by functional magnetic resonance imaging
timeFrame: Assessed at baseline (week 1) and end of treatment (week 13)
measure: Change in Beck Depression Inventory
timeFrame: Assessed at baseline (week 1), throughout treatment phase (weeks 3-11), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in PSG Sleep Efficiency
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Insomnia Severity Index (ISI) Scale Score
timeFrame: Assessed at baseline (week 1), throughout treatment phase (weeks 3-11), end of treatment (week 13), and 6-month follow-up (week 39)
Secondary outcomes:
measure: Change in Columbia Suicide Severity Rating Scale
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Actigraph Sleep Onset Latency (SOL) as a Measure of Sleep Continuity
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Actigraph Number of Arousals as a Measure of Sleep Continuity
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Actigraph Wake After Sleep Onset (WASO) as a Measure of Sleep Continuity
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Actigraph Total Sleep Time (TST) as a Measure of Sleep Continuity
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Actigraph Sleep Efficiency (SE) as a Measure of Sleep Continuity
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in PSG Number of Arousals as a Measure of Sleep Architecture
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in PSG Wake After Sleep Onset (WASO) as a Measure of Sleep Architecture
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in PSG Total Sleep Time (TST) as a Measure of Sleep Architecture
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in PSG Sleep Efficiency (SE) as a Measure of Sleep Architecture
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Sleep Physiology measured by PSG
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in 36-Item Short Form Survey (SF-36) Score
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Beck Anxiety Inventory
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
measure: Change in Respiratory Sinus Arrhythmia (RSA)- measured by PSG
timeFrame: Assessed at baseline (week 1), end of treatment (week 13), and 6-month follow-up (week 39)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
References: