A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety

Depression Clinical Trial

Official title:

A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04424407
• Other study ID #: IRB-56961
• Secondary ID: R61MH120245
• Status: Completed
• Phase: N/A
• Start date: May 28, 2021
• Est. completion date: March 23, 2024

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Several lines of evidence suggest that unhealthy sleep patterns contribute to depressive symptoms through disruption of brain networks that regulate emotional functions. However, we do not yet know to what degree the emotion regulation brain network is modified by the restoration of sleep, or whether the degree to which a sleep intervention modifies these neural targets mediates reductions in other depressive symptoms including suicidality.

The overall aim is to test the efficacy of an established sleep intervention (Cognitive Behavioral Therapy for Insomnia (CBT-I)) in reducing depressive symptoms through improving emotion regulation brain function in individuals with elevated depressive symptoms and clinically meaningful sleep disturbance.

In this study, we will assess feasibility of recruitment and retention as well as target engagement. Target engagement is defined as the treatment effect on increasing mPFC-amydgala connectivity, and/or decreasing amygdala reactivity during emotion reactivity and regulation paradigms. Participants will be 70 adults experiencing at least moderate sleep disturbances and who also have elevated anxious and/or depressive symptoms. Emotion distress and sleep disruption will be assessed prior to, and weekly while receiving six Cognitive Behavioral Therapy for Insomnia (CBT-I) across a period of 8 weeks. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: March 23, 2024
• Est. primary completion date: March 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 60 Years

Eligibility

Inclusion Criteria:

• Ages 25-60

• Subjective complaint of sleep disturbance for = 3 months (ISI>15)

• Subjective complaint of depression (BDI=14) and not at imminent risk for suicide, as measured by CSSRS assessment

• 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

• Medications that would significantly impact sleep, alertness, or mood

• >14 alcoholic drinks per week or >4 drinks per occasion

• General medical condition, disease or neurological disorder that interferes with the assessments or outpatient participation

• Substance abuse or dependence

• Mild traumatic brain injury

• Severe impediment to vision, hearing and/or hand movement, likely to interfere with the ability to follow study protocols

• Pregnant or breast feeding

• Current or lifetime history of bipolar disorder or psychosis

• Current or or expected cognitive behavior therapy or other evidence-based psychotherapies for another condition

• Received CBT-I within the past year

• Acute or unstable chronic illness

• Current exposure to trauma, or exposure to trauma within the past 3 months

• Working a rotating shift that overlaps with 2400h.

• Presence of suicidal ideations representing imminent risk as determined by the empirically-supported, standardized suicide risk assessment" to the exclusion criteria

• Individuals who are not CPAP adherent or have untreated OSA of moderate severity or worse (AHI = 15)

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Insomnia
• Sleep Initiation and Maintenance Disorders

Intervention

Behavioral:
• Cognitive Behavioral Therapy for Insomnia
Participants will meet with a psychologist once a week for six weeks to complete a brief CBT-I intervention. Cognitive Behavioral Therapy for Insomnia consists of a cognitive therapy and a behavioral therapy. The cognitive therapy is designed to identify incorrect ideas about sleep, challenge their validity, and replace them with correct information. This therapy tries to reduce worry, anxiety, and fear that one won't sleep by providing accurate information about sleep. The behavioral therapy increases sleep quality by limiting excessive time spent in bed to increase homeostatic sleep drive and sleep consolidation.

Locations

Country	Name	City	State
United States	Stanford University	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Emotion Regulation Network brain activation as assessed by functional magnetic resonance imaging	During functional magnetic resonance imaging the Emotion Regulation Network will be engaged by emotional tasks, and circuit activation will be quantified by blood flow in regions of interest.	Assessed at week 0 and week 11
Primary	Change in Emotion Regulation Network brain connectivity as assessed by functional magnetic resonance imaging	During functional magnetic resonance imaging the Emotion Regulation Network will be engaged by emotional tasks, and circuit connectivity will be quantified by the correlation of the blood flow between regions of interest.	Assessed at week 0 and week 11
Primary	Change in Beck Depression Inventory	This measure is of the Beck Depression Inventory-II total score after excluding one sleep item. The average item score for the remaining 20 items will be multiplied by 21 (the original number of items), to create a modified depression scale that maintains the original range (ranges: 0-13 minimal, 14-19 mild, 20-28 moderate, and 29-63 severe).; The BDI-II is a 21-item self-report scale with high validity and reliability that assesses the severity of depression symptoms. The depression items consist of: sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, irritability, changes in appetite, concentration difficulty, tiredness or fatigue, and loss of interest in sex. Items are scored from 0 to 3, and higher scores indicate greater levels of severity.	Assessed at week 0 and week 11
Primary	Change in PSG Sleep Efficiency	Sleep efficiency (SE) is the percentage of total time in bed actually spent sleeping. Based on the overnight PSG sleep recording, SE will be calculated as the total time (minutes) spent asleep (sum of Stages N1, N2, N3, and REM) divided by the total time (minutes) in bed, and multiplied by 100.	Assessed at week 0 and week 11
Secondary	Change in Columbia Suicide Severity Rating Scale	The Columbia Suicide Severity Rating Scale is a 12-item checklist that was designed to quantify the severity of suicidal ideation and behavior. It is composed of two parts. The first six questions ask about suicidal ideation and behavior in the past month while the last six questions ask about suicidal ideation and behavior since the last visit. The CSSRS has been proven to be reliable and valid. It has also been shown to have high sensitivity and specificity to the different suicidal behavior classifications.	Assessed at week 0 and week 11
Secondary	Change in Actigraph Sleep Onset Latency (SOL) as a Measure of Sleep Continuity	Sleep Onset Latency (SOL) is the time (minutes) from "lights out" to actually falling asleep (sleep onset).	Assessed at week 0 and week 11
Secondary	Change in Actigraph Number of Arousals as a Measure of Sleep Continuity	Number of Arousals is determined by number of times of awakening as seen on the actigraph data.	Assessed at week 0 and week 11
Secondary	Change in Actigraph Wake After Sleep Onset (WASO) as a Measure of Sleep Continuity	Wake After Sleep Onset (WASO) are periods of wakefulness occurring after sleep onset, before final awakening (sleep offset).	Assessed at week 0 and week 11
Secondary	Change in Actigraph Total Sleep Time (TST) as a Measure of Sleep Continuity	Total Sleep Time (TST) is the total time spent asleep, from the start of sleep onset to sleep offset subtracting any periods of wakefulness.	Assessed at week 0 and week 11
Secondary	Change in Actigraph Sleep Efficiency (SE) as a Measure of Sleep Continuity	Sleep Efficiency (SE) is calculated as TST divided by total time spent in bed, multiplied by 100.	Assessed at week 0 and week 11
Secondary	Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture	Sleep Onset Latency (SOL) is the time (minutes) from "lights out" or start of total recording time, to actually falling asleep as indicated by EEG changes.	Assessed at week 0 and week 11
Secondary	Change in PSG Number of Arousals as a Measure of Sleep Architecture	Number of Arousals is determined by number of times of awakening by EEG changes.	Assessed at week 0 and week 11
Secondary	Change in PSG Wake After Sleep Onset (WASO) as a Measure of Sleep Architecture	Wake After Sleep Onset (WASO) are periods of wakefulness occurring after sleep onset, before final awakening (sleep offset) measured by EEG changes.	Assessed at week 0 and week 11
Secondary	Change in PSG Total Sleep Time (TST) as a Measure of Sleep Architecture	Total Sleep Time (TST) is the total time (minutes) spent asleep, from the start of sleep onset to sleep offset, subtracting any periods of wakefulness. TST includes stages N1, N2, N3, and REM sleep.	Assessed at week 0 and week 11
Secondary	Change in PSG Sleep Efficiency (SE) as a Measure of Sleep Architecture	Sleep Efficiency (SE) is calculated as TST divided by total time spent in bed, multiplied by 100.; Duration of non-rapid eye movement (NREM) sleep includes stages N1, N2, and N3, and is measured in minutes. The duration of sleep outside of those stages that is associated with specific EEG stages is REM sleep.	Assessed at week 0 and week 11
Secondary	Change in Sleep Physiology measured by PSG	Topographical EEG power spectral density analysis associated with sleep stages will be calculated in the Delta (0.5-Hz), Theta (4-7Hz), Alpha (7-11Hz), Sigma (12-15Hz), Beta-1 (15-20Hz), Beta-2 (20-35Hz) and Gamma (35-45Hz) bands, according to published methods.	Assessed at week 0 and week 11
Secondary	Change in Insomnia Severity Index (ISI) Scale Score	Subjective ratings of sleep disturbance and insomnia severity will be assessed with the Insomnia Severity Index. The Insomnia Severity Index (ISI) is a 7-item self-report measure of insomnia type, severity, and impact on functioning. The items consist of severity of sleep onset, sleep maintenance, early morning awakenings, sleep dissatisfaction, interference with daytime functioning, noticeability of sleep problems by others, and distress caused by sleep difficulties. Items are scored from 0 to 4 (0 = no problem, 4 = very severe problem). Score ranges of insomnia are: 0-7 absent, 8-14 sub-threshold, 15-21 moderate, and 22-28 severe. The ISI has good validity and reliability.	Assessed at week 0 and week 11
Secondary	Change in 36-Item Short Form Survey (SF-36) Score	The SF-36 measures health-related quality of life based on eight domains: limitations in physical activities because of health problems, limitations in social activities because of physical or emotional problems, limitations in usual role activities because of physical health problems, bodily pain, general mental health (psychological distress and well-being), limitations in usual role activities because of emotional problems, vitality (energy and fatigue), and general health perceptions. Items are recoded then averaged together to create each scale. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.	Assessed at week 0 and week 11
Secondary	Change in Beck Anxiety Inventory	The BAI is a 21-item self-report scale that assesses the severity of anxiety symptoms.; Items are scored from 0 to 3 (0 = not at all, 3 = severe). Higher scores indicate greater levels of severity, and the ranges for anxiety levels are: 0-9 normal to minimal, 10-18 mild to moderate, 19-29 moderate to severe, and 30-63 severe. The BAI consists of two factors: somatic and cognitive.	Assessed at week 0 and week 11
Secondary	Change in Respiratory Sinus Arrhythmia (RSA)- measured by PSG	RSA is the phenomenon of an increased heart rate during inhalation and a decreased heart rate during exhalation. Since these fluctuations are controlled mainly by vagal influences on the heart, RSA serves as a reliable metric for measuring parasympathetic activity. RSA has been proven to be a reliable measure of emotion regulation and emotional responding in numerous studies.	Assessed at week 0 and week 11