Sleep Modulation as Antidepressant Randomized Trial

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the effects of phase-targeted auditory stimulation in depressed patients and healthy controls. The main questions it aims to answer are: Is auditory down-phase stimulation efficient in improving depression symptoms as compared to sham stimulation? Can mood and other outcomes be prospectively estimated by multi-parametric passive data? Participants will perform auditory stimulation using a wearable device at home and provide data on their phone usage and activity. Researchers will compare depressed patients and healthy participants to see if auditory down-phase stimulation effects them differently.

Detailed Description
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This study consists of two parts: CLINICAL TRIAL PART: This part will be conducted in depressed and age- and sex-matched healthy participants. It has a double-blind, randomized crossover design. Each participant will undergo 1 week of baseline monitoring, followed by 1 week of in-home stimulation and 1 week of placebo condition interleaved with 1 week wash-out period. The last night of each intervention week will take place in a laboratory setting. A final week of follow-up will follow the second intervention week. The following data is collected: Single-channel EEG (at home) and high-density electroencephalogram (hdEEG) (in laboratory) MR imaging Daily questionnaires Passive behavioural and physiological measurements MONITORING PART: This observational study part will be conducted in depressed participants only. Each participant will undergo 5 weeks of remote monitoring using wearable devices and smartphones. Patients not eligible for the CLINICAL TRIAL PART, or that meet an exclusion criterion at any point in the study, can be assigned to this study part.

Official Title
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Assessing the Symptomatic Benefit of Slow-wave Activity Reduction Using Wearables and Sensor-based Characterization of Depression: a Randomized, Counter-balanced Crossover Study

Conditions
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Healthy, Depression

Intervention / Treatment
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* Device: Phase-targeted auditory stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults aged 18-55 years Motivated, no aversion against technology Able to give informed consent as documented by signature, and to follow the technical instructions Able to understand and speak German or English as required for the interview (HDRS) and to answer the questionnaires Diagnosis of depression according to DSM-5 criteria (depressed) OR no diagnosis of depression AND no depressive episode in the history (healthy) ≥17 points in Hamilton Depression Rating Score (HDRS, corresponding to at least moderate-mild depression, depressed) OR <8 points in HDRS (healthy) Stable or no pharmacological antidepressant therapy, no acute suicidal tendency (depressed) Exclusion Criteria: Pregnant or lactating women, women planning to get pregnant during the study period Bipolar disorder or psychotic symptoms in the history Relevant disease or medication that could present a risk for the participant or that could influence study findings Known sleep apnea (diagnosed or ESS ≥10 points) or periodic limb movement syndrome Known alcoholism or drug abuse Diagnosed hearing impairment/presbycusis Irregular intake of centrally depressing or stimulating medication known to alter sleep EEG (e.g., benzodiazepines) History of traumatic brain injury (except for concussion) or neurosurgical procedures/operations Known epilepsy or for any reason, intracranial space-occupying lesions or (infectious or autoimmune) inflammatory diseases of the central nervous system Shift workers Inability to follow the procedures of the study, e.g., due to language problems, dementia, etc. Skin diseases/skin problems (in the face/ear/chest area) or allergies that could be aggravated by electrode application Conditions that may interfere with the MRI (e.g., MR unsafe cardiac pacemaker or a defibrillator, MR unsafe metal in or near the head, spinal cord, eyes, or in the chest) Indications of sleep apnea (Apnea Hypopnea Index >15/h) or periodic limb movement syndrome (PLMS index >15/h) in the screening night Low stimulation efficiency (<500 stimulations detected by the device) in the screening night or in 3 subsequent home recording nights, e.g., due to very little deep sleep Participation in another clinical trial during the study period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Auditory stimulation first<br>This study group receives auditory stimulation in the first intervention week (second week of trial) and sham stimulation in the second intervention week (fourth week of trial). | Device: Phase-targeted auditory stimulation<br>* Bursts of pink noise (50 ms) played during deep non-REM sleep at specific phases of sleep slow waves.<br>|
| Other: Sham stimulation first<br>This study group receives sham stimulation in the first intervention week (second week of trial) and auditory stimulation in the second intervention week (fourth week of trial). | Device: Phase-targeted auditory stimulation<br>* Bursts of pink noise (50 ms) played during deep non-REM sleep at specific phases of sleep slow waves.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression severity | Change in Hamilton Depression Rating Score (HDRS) as compared to baseline score. The 17-item HDRS is on a scale of 0-52 with higher scores indicating more severe symptomatology. | baseline; after first intervention week; after second intervention week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Change in response rate in the Hamilton Depression Rating Score. Response is defined as a reduction of at least 50% compared to baseline or score <8 points. | after first intervention week; after second intervention week | 
| Subjective momentary sleepiness | Compare momentary sleepiness using the Karolinska Sleepiness Scale (KSS) between the two intervention weeks. KSS scores range from 1-10 with higher scores indicating higher sleepiness. | first intervention week; second intervention week | 
| Electroencephalographic (EEG) topography | Change in topography of the electric brain activity (EEG) during sham and stimulation night in the laboratory. Spectral decomposition of the signal will be performed to compare single frequency bins and established frequency bands (delta, theta, alpha, sigma, beta, gamma). | last night of first intervention week; last night of second intervention week | 
| MR Spectroscopy | Changes in Glutamate/Glutamine (combined as Glx) in the dorsolateral prefrontal cortex as assessed by magnetic resonance spectroscopy between sham and stimulation weeks. | after first intervention week; after second intervention week | 
| Brain connectivity | Change in resting state functional connectivity (fMRI) between sham and stimulation weeks. | after first intervention week; after second intervention week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Depression, Auditory stimulation, Sleep