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

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ClinicalTrials.gov Identifier: NCT04424407
Recruitment Status : Not yet recruiting
First Posted : June 11, 2020
Last Update Posted : June 11, 2020
Sponsor:
Information provided by (Responsible Party):
Andrea Goldstein-Piekarski, Stanford University

Brief 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-amygala 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.


Condition or disease Intervention/treatment Phase
Insomnia Depression Behavioral: Cognitive Behavioral Therapy for Insomnia Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single-armed trial. All participants will receive Cognitive Behavioral Therapy for Insomnia
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety
Estimated Study Start Date : September 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
CBT-I 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.
Other Name: CBT-I




Primary Outcome Measures :
  1. Change in Emotion Regulation Network brain activation as assessed by functional magnetic resonance imaging [ Time Frame: Assessed at week 0 and week 11 ]
    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.

  2. Change in Emotion Regulation Network brain connectivity as assessed by functional magnetic resonance imaging [ Time Frame: Assessed at week 0 and week 11 ]
    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.

  3. Change in Beck Depression Inventory [ Time Frame: Assessed at week 0 and week 11 ]

    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.


  4. Change in PSG Sleep Efficiency [ Time Frame: Assessed at week 0 and week 11 ]
    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.


Secondary Outcome Measures :
  1. Change in Columbia Suicide Severity Rating Scale [ Time Frame: Assessed at week 0 and week 11 ]
    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.

  2. Change in Actigraph Sleep Onset Latency (SOL) as a Measure of Sleep Continuity [ Time Frame: Assessed at week 0 and week 11 ]
    Sleep Onset Latency (SOL) is the time (minutes) from "lights out" to actually falling asleep (sleep onset).

  3. Change in Actigraph Number of Arousals as a Measure of Sleep Continuity [ Time Frame: Assessed at week 0 and week 11 ]
    Number of Arousals is determined by number of times of awakening as seen on the actigraph data.

  4. Change in Actigraph Wake After Sleep Onset (WASO) as a Measure of Sleep Continuity [ Time Frame: Assessed at week 0 and week 11 ]
    Wake After Sleep Onset (WASO) are periods of wakefulness occurring after sleep onset, before final awakening (sleep offset).

  5. Change in Actigraph Total Sleep Time (TST) as a Measure of Sleep Continuity [ Time Frame: Assessed at week 0 and week 11 ]
    Total Sleep Time (TST) is the total time spent asleep, from the start of sleep onset to sleep offset subtracting any periods of wakefulness.

  6. Change in Actigraph Sleep Efficiency (SE) as a Measure of Sleep Continuity [ Time Frame: Assessed at week 0 and week 11 ]
    Sleep Efficiency (SE) is calculated as TST divided by total time spent in bed, multiplied by 100.

  7. Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture [ Time Frame: Assessed at week 0 and week 11 ]
    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.

  8. Change in PSG Number of Arousals as a Measure of Sleep Architecture [ Time Frame: Assessed at week 0 and week 11 ]
    Number of Arousals is determined by number of times of awakening by EEG changes.

  9. Change in PSG Wake After Sleep Onset (WASO) as a Measure of Sleep Architecture [ Time Frame: Assessed at week 0 and week 11 ]
    Wake After Sleep Onset (WASO) are periods of wakefulness occurring after sleep onset, before final awakening (sleep offset) measured by EEG changes.

  10. Change in PSG Total Sleep Time (TST) as a Measure of Sleep Architecture [ Time Frame: Assessed at week 0 and week 11 ]
    Total Sleep Time (TST) is the total time (minutes) spent asleep, from the start of sleep onsetto sleep offset, subtracting any periods of wakefulness. TST includes stages N1, N2, N3, and REM sleep.

  11. Change in PSG Sleep Efficiency (SE) as a Measure of Sleep Architecture [ Time Frame: Assessed at week 0 and week 11 ]

    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.


  12. Change in Sleep Physiology measured by PSG [ Time Frame: Assessed at week 0 and week 11 ]
    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.

  13. Change in Insomnia Severity Index (ISI) Scale Score [ Time Frame: Assessed at week 0 and week 11 ]
    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.

  14. Change in Social and Occupational Functioning Assessment Scale (SOFAS) [ Time Frame: Assessed at week 0 and week 11 ]
    The SOFAS is a clinician-rated, global rating scale of overall level of current functioning based on social and occupational functioning. The scoring considers impairments in functioning directly related to physical and/or mental impairments. Scores range from 0 - 100, with lower scores indicating lower levels of functioning.

  15. Change in World Health Organization quality of life assessment (WHOQoL) [ Time Frame: Assessed at week 0 and week 11 ]
    The WHOQOL-BRIEF is a 26-item brief version of the WHOQOL, that measures quality of life based on six domains: physical health, psychological state, level of independence, social relations, environment, and spirituality/religion/personal beliefs. Four general items about subjective overall QOL and health are also included. Only domain and general item scores are calculated in the WHOQOL-BREF. Items are scored on scales of 1 to 5, and higher scores indicate higher quality of life.

  16. Change in Beck Anxiety Inventory [ Time Frame: Assessed at week 0 and week 11 ]

    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.


  17. Change in Respiratory Sinus Arrhythmia (RSA)- measured by PSG [ Time Frame: Assessed at week 0 and week 11 ]
    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.



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Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • Caffeine consumption ≤ 3 8 ounce cups prior to lunch every day for ≥ 3 weeks prior to treatment
  • Written informed consent.

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 de novo cognitive behavior therapy 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04424407


Locations
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United States, California
Stanford University
Palo Alto, California, United States, 94304
Contact: Andrea N Goldstein-Piekarski    650-497-9414    agoldpie@stanford.edu   
Contact: Kathleen O'Hora    650-497-9346    kohora@stanford.edu   
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Andrea Goldstein-Piekarski, PhD Stanford University
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Responsible Party: Andrea Goldstein-Piekarski, Clinical Assistant Professor, Stanford University
ClinicalTrials.gov Identifier: NCT04424407    
Other Study ID Numbers: IRB-56961
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: June 11, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andrea Goldstein-Piekarski, Stanford University:
Insomnia
Depression
Anxiety
CBT-I
Cognitive Behavioral Therapy for Insomnia
Additional relevant MeSH terms:
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Sleep Initiation and Maintenance Disorders
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases