InsomniaNCT04424407
A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety
A study testing Cognitive Behavioral Therapy for Insomnia in people with Insomnia and Depression, run by Stanford University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 25 to 60 years
- Conditions the study is for
- Insomnia, Depression
- What is being tested?
- Cognitive Behavioral Therapy for Insomnia
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2021to 23 Mar 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Ages 25-60
- Subjective complaint of sleep disturbance for ≥ 3 months (ISI≥10)
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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-amygdala 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.
- Conditions
- Insomnia, Depression
- Being tested
- Cognitive Behavioral Therapy for Insomnia
- Keywords
- Insomnia, Depression, Anxiety, CBT-I, Cognitive Behavioral Therapy for Insomnia
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, Depression, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral Therapy for InsomniaBehavioural
Also called CBT-I
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.
| Study group | Role | What they receive |
|---|---|---|
| CBT-I | Other | Not described Receives: Behavioral: Cognitive Behavioral Therapy for Insomnia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
The Conscious condition of the Facial Expressions of Emotion task measures supraliminal (without backward masking) emotional face processing. Amygdala activation while viewing threat-related emotional faces relative to neutral faces was quantified using functional magnetic resonance imaging (fMRI) as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional faces using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to emotional faces, relative to neutral faces. A negative value for the change in amygdala activation means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes.
Measured: Assessed at week 0 and week 11
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Nonconscious Condition) as Assessed by Functional Magnetic Resonance Imaging
The Nonconscious condition of the Facial Expressions of Emotion task measures subliminal (with backward masking) emotional face processing. Amygdala activation while viewing threat-related emotional faces relative to neutral faces was quantified using fMRI as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional faces using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to emotional faces, relative to neutral faces. A negative value for the change in amygdala activation means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes.
Measured: Assessed at week 0 and week 11
Change in Amygdala Activation During the Emotion Regulation Scenes Task
Participants are asked to "look" or "decrease" their emotional response to negative and neutral valence images taken from the International Affective Picture System. Amygdala activation while viewing emotional scenes relative to neutral scenes, and while passively viewing emotional scenes relative to down-regulating emotion, was quantified using fMRI as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional scenes or while downregulating using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to the task demands, and a negative value means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes
Measured: Assessed at week 0 and week 11
Change in Amygdala-Medial Prefrontal Cortex Connectivity During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
This outcome tested whether amygdala connectivity with regions of the mPFC was changed following treatment using psychophysiological interaction (PPI) analysis for this contrast/task. Regions of the mPFC include: dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), dorsomedial prefrontal cortex (dmPFC), subgenual anterior cingulate cortex (sgACC), pregenual anterior cingulate cortex (pACC). PPI analyses produce a beta weight for each participant at each timepoint, and represents the degree to which the connectivity of the amygdala and mPFC is modulated by task conditions. A positive value means average connectivity increases in the task-contrast, and a positive value for the change score means an increase in average connectivity following CBT-I treatment. It is theorized that higher amygdala connectivity is associated with better outcomes.
Measured: Assessed at week 0 and week 11
Change in Beck Depression Inventory (BDI)
This measure is of the Beck Depression Inventory-II total score after excluding one sleep item.
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 summed to create an overall score of 0 to 63. higher scores indicate greater levels of severity. The ranges for depression are: 0-13 minimal, 14-19 mild, 20-28 moderate, and 29-63 severe. A negative change score means that average depression symptom severity was reduced following CBT-I treatment.
Measured: Assessed at week 0 and week 11
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. A positive change score means average sleep efficiency increased following CBT-I treatment.
Measured: Assessed at week 0 and week 11
Secondary outcomes (16)
Change in Beck Scale of Suicidal Ideation Total Score
The Beck Scale of Suicidal Ideation (BSSI) is designed to assess the severity of suicidal ideation over the past week. The total score is derived from the sum of the first 19 items, creating an overall score ranging from 0 to 38. Scores of 0 are interpreted as no suicidal ideation, 1-8 as low levels, 9-16 as moderate levels, and 17-38 as high levels. A negative change score means an average reduction in suicidal ideation following CBT-I treatment.
Measured: Assessed at week 0 and week 11
Change in Columbia Suicide Severity Rating Scale
The Columbia Suicide Severity Rating Scale (CSSRS) 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. The CSSRS does not provide a numerical score but categorizes risk levels based on responses. We report the proportions of risk at each timepoint.
Measured: Assessed at week 0 and week 11
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).
Measured: Assessed at week 0 and week 11
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.
Measured: Assessed at week 0 and week 11
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).
Measured: Assessed at week 0 and week 11
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.
Measured: Assessed at week 0 and week 11
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.
Measured: Assessed at week 0 and week 11
Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture
Sleep onset latency is the time it takes to fall asleep, specifically the amount of time in minutes from "LightsOff", which is the time at which the participant started trying to sleep, to stage 1 sleep. A negative change score means it took less time to fall asleep following CBT-I treatment.
Measured: Assessed at week 0 and week 11
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. A negative change score means on average there were fewer overnight arousals following CBT-I treatment.
Measured: Assessed at week 0 and week 11
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. A negative change value means there was less WASO on average after CBT-I treatment.
Measured: Assessed at week 0 and week 11
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. A positive change score means the average TST increased following CBT-I.
Measured: Assessed at week 0 and week 11
Change in Sleep Physiology Measured by PSG
Fronto-central 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. A positive change score means there was an increase in absolute power in the specified frequency band following CBT-I treatment.
Measured: Assessed at week 0 and week 11
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), then summed to create an overall score of 0 to 28. 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. A negative change score means average insomnia symptoms improved following CBT-I treatment.
Measured: Assessed at week 0 and week 11
Change in 36-Item Short Form Survey (SF-36) Score
The SF-36 measures health-related quality of life based on eight domains: physical activity, social activities, limitations in activities due to physical health problems, bodily pain, general mental health, limitations in activities due to emotional problems, vitality, and general health perceptions. Items are recoded then averaged together to create each an average score for all items that the respondent answered. The eight subscales are then into two component summary t-scores (Mental and Physical Component Summary t-scores), each with a mean of 50 and a standard deviation of 10. A t-score higher than 50 means better mental or physical health than the general population, and a t-score below 50 means worse than the general population. Instructions for scoring these component scores recommends that they be set to missing if any subscales are missing. A positive change score means the Component Summary Score improved following CBT-I.
Measured: Assessed at week 0 and week 11
Change in Beck Anxiety Inventory (BAI)
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), then summed to create an overall score range of 0 to 63. 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. A negative change score means that average anxiety symptom severity was reduced following CBT-I treatment.
Measured: Assessed at week 0 and week 11
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.
Measured: Assessed at week 0 and week 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start28 May 2021
- Primary completion23 Mar 2024
- Study completion23 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InsomniaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-armed trial. All participants will receive Cognitive Behavioral Therapy for Insomnia
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Andrea Goldstein-Piekarski, Stanford University
- Investigators
- Andrea Goldstein-Piekarski, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04424407
- Sponsor's protocol ID
- IRB-56961
- Other IDs
- R61MH120245
- Status last verified
- Sep 2025
- First submitted
- 3 Jun 2020
- Last updated
- 15 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Krause AJ, Osorno R, Solomon NL, Ahmadi M, Lam P, Magana O, Blozyte-Sakenis E, Harris LN, Babros MC, Izabel SS, Bernert RA, Williams LM, Gross JJ, Ma J, Lazzeroni LC, Yesavage JA, Manber R, Saletin JM, Goldstein-Piekarski AN. Examining fronto-limbic brain and sleep mechanisms of antidepressant effects in cognitive-behavioral therapy for insomnia. Neuropsychopharmacology. 2026 Aug;51(9):1657-1668. doi: 10.1038/s41386-026-02431-0. Epub 2026 May 7.
PubMed 42098309
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety
- ClinicalTrials.gov ID
- NCT04424407
- Acronym / sponsor ID
- IRB-56961
- Conditions
- Insomnia, Depression
- Keywords
- Insomnia, Depression, Anxiety, CBT-I, Cognitive Behavioral Therapy for Insomnia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 28 May 2021 (actual)
- Primary completion
- 23 Mar 2024 (actual)
- Study completion
- 23 Mar 2024 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 15 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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-amygdala 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-armed trial. All participants will receive Cognitive Behavioral Therapy for Insomnia
| Arm | Type | Receives |
|---|---|---|
| CBT-I | Other | Behavioral: Cognitive Behavioral Therapy for Insomnia |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Ages 25-60
- Subjective complaint of sleep disturbance for ≥ 3 months (ISI≥10)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral Therapy for InsomniaAlso: CBT-IParticipants 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. | Behavioural | CBT-I |
Primary outcome
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
Time frame: Assessed at week 0 and week 11
The Conscious condition of the Facial Expressions of Emotion task measures supraliminal (without backward masking) emotional face processing. Amygdala activation while viewing threat-related emotional faces relative to neutral faces was quantified using functional magnetic resonance imaging (fMRI) as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional faces using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to emotional faces, relative to neutral faces. A negative value for the change in amygdala activation means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes.
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Nonconscious Condition) as Assessed by Functional Magnetic Resonance Imaging
Time frame: Assessed at week 0 and week 11
The Nonconscious condition of the Facial Expressions of Emotion task measures subliminal (with backward masking) emotional face processing. Amygdala activation while viewing threat-related emotional faces relative to neutral faces was quantified using fMRI as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional faces using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to emotional faces, relative to neutral faces. A negative value for the change in amygdala activation means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes.
Change in Amygdala Activation During the Emotion Regulation Scenes Task
Time frame: Assessed at week 0 and week 11
Participants are asked to "look" or "decrease" their emotional response to negative and neutral valence images taken from the International Affective Picture System. Amygdala activation while viewing emotional scenes relative to neutral scenes, and while passively viewing emotional scenes relative to down-regulating emotion, was quantified using fMRI as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional scenes or while downregulating using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to the task demands, and a negative value means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes
Change in Amygdala-Medial Prefrontal Cortex Connectivity During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
Time frame: Assessed at week 0 and week 11
This outcome tested whether amygdala connectivity with regions of the mPFC was changed following treatment using psychophysiological interaction (PPI) analysis for this contrast/task. Regions of the mPFC include: dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), dorsomedial prefrontal cortex (dmPFC), subgenual anterior cingulate cortex (sgACC), pregenual anterior cingulate cortex (pACC). PPI analyses produce a beta weight for each participant at each timepoint, and represents the degree to which the connectivity of the amygdala and mPFC is modulated by task conditions. A positive value means average connectivity increases in the task-contrast, and a positive value for the change score means an increase in average connectivity following CBT-I treatment. It is theorized that higher amygdala connectivity is associated with better outcomes.
Change in Beck Depression Inventory (BDI)
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 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 summed to create an overall score of 0 to 63. higher scores indicate greater levels of severity. The ranges for depression are: 0-13 minimal, 14-19 mild, 20-28 moderate, and 29-63 severe. A negative change score means that average depression symptom severity was reduced following CBT-I treatment.
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. A positive change score means average sleep efficiency increased following CBT-I treatment.
16 secondary outcomes
Change in Beck Scale of Suicidal Ideation Total Score
Time frame: Assessed at week 0 and week 11
Change in Columbia Suicide Severity Rating Scale
Time frame: Assessed at week 0 and week 11
Change in Actigraph Sleep Onset Latency (SOL) as a Measure of Sleep Continuity
Time frame: Assessed at week 0 and week 11
Change in Actigraph Number of Arousals as a Measure of Sleep Continuity
Time frame: Assessed at week 0 and week 11
Change in Actigraph Wake After Sleep Onset (WASO) as a Measure of Sleep Continuity
Time frame: Assessed at week 0 and week 11
Change in Actigraph Total Sleep Time (TST) as a Measure of Sleep Continuity
Time frame: Assessed at week 0 and week 11
Change in Actigraph Sleep Efficiency (SE) as a Measure of Sleep Continuity
Time frame: Assessed at week 0 and week 11
Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture
Time frame: Assessed at week 0 and week 11
Change in PSG Number of Arousals as a Measure of Sleep Architecture
Time frame: Assessed at week 0 and week 11
Change in PSG Wake After Sleep Onset (WASO) as a Measure of Sleep Architecture
Time frame: Assessed at week 0 and week 11
Change in PSG Total Sleep Time (TST) as a Measure of Sleep Architecture
Time frame: Assessed at week 0 and week 11
Change in Sleep Physiology Measured by PSG
Time frame: Assessed at week 0 and week 11
Change in Insomnia Severity Index (ISI) Scale Score
Time frame: Assessed at week 0 and week 11
Change in 36-Item Short Form Survey (SF-36) Score
Time frame: Assessed at week 0 and week 11
Change in Beck Anxiety Inventory (BAI)
Time frame: Assessed at week 0 and week 11
Change in Respiratory Sinus Arrhythmia (RSA)- Measured by PSG
Time frame: Assessed at week 0 and week 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42098309Krause AJ, Osorno R, Solomon NL, Ahmadi M, Lam P, Magana O, Blozyte-Sakenis E, Harris LN, Babros MC, Izabel SS, Bernert RA, Williams LM, Gross JJ, Ma J, Lazzeroni LC, Yesavage JA, Manber R, Saletin JM, Goldstein-Piekarski AN. Examining fronto-limbic brain and sleep mechanisms of antidepressant effects in cognitive-behavioral therapy for insomnia. Neuropsychopharmacology. 2026 Aug;51(9):1657-1668. doi: 10.1038/s41386-026-02431-0. Epub 2026 May 7.
- Individual participant dataSharing planned: No
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Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
Evaluation of Cognitive Behavioral Therapy for Insomnia (CBT-I) in Individuals With Mild Traumatic Brain Injury (mTBI)
Sleep Architecture, Mild Traumatic Brain Injury
RecruitingPhase 3
A Trial to See if Daridorexant Can Help Adults and Elderly People With Insomnia Sleep Better During the Night and Function Better During the Day
Insomia Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Goldstein-Piekarski, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Behavioral Therapy for Insomnia in people with Insomnia and Depression, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging (time frame: Assessed at week 0 and week 11). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04424407, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2025.