Auditory Slow Wave Enhancement After Concussion

Study Overview
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Brief Summary
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The prevalence of a traumatic brain injury (TBI) in children and adolescents is around 30% with 70-90% being classified as mild (concussion). Because the brain of a child is still developing, a TBI can have devastating effects and possibly creates lifetime challenges. Sleep seems to play an important role in the post-concussion recovery process. Auditory stimulation during sleep has been shown to reliably boost slow waves, a solid marker for the depth of sleep, and can thus be used to deepen sleep. This study aims to investigate the effects of sleep enhancement via auditory stimulation on recovery after a concussion in children and adolescents in their home. Therefore, half of the patients receive one week of auditory stimulation during deep sleep at their home using a mobile device. The other half follows the same study protocol, but no tones are administered (sham). Cognitive tests as well as symptom questionnaires are used to assess the recovery process. It is hypothesized that the patients in the intervention group will recover better than the ones who haven't received the intervention. Additionally, a group of children and adolescents who never sustained a concussion is included as a control.

Detailed Description
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In total, 120 participants are planned: 60 patients (30 intervention, 30 sham) and 60 controls (30 intervention, 30 sham). This was estimated from a power analysis and based on previous results. Patients are recruited from the University Children's Hospital Zurich. At first, the participants will complete a baseline assessment of neuropsychological measures (cognitive tests and questionnaires). After completion of the baseline assessment, the participants receive deep sleep enhancement with auditory stimulation for seven nights, but half of them will only receive sham stimulation (device application, but no stimulation). Additionally, they wear an actigraph throughout the whole week. Afterwards, they fill in again some questionnaires (intermediate assessment). One month after study inclusion, the first follow-up will take place where neuropsychological and (optionally) neurological measures will be collected. The second follow-up takes place six months after study inclusion and involves again filling in questionnaires about post-concussive symptoms. The study will be monitored regularly in terms of data validation and source data verification. Adverse events and device deficiencies are carefully documented and reported according to the guidelines of swissmedic and the responsible ethics committee.

Official Title
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The Effect of Sleep and Slow Wave Enhancement on Recovery From a Concussion in Children and Adolescents: A Longitudinal, Randomized, Double-Blind, and Sham-Controlled Study

Conditions
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Concussion Post Syndrome

Intervention / Treatment
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* Device: Auditory Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature Age between 6 and 18 years Good knowledge of German of the patient and at least one legal representative Patients: Presentation to the Emergency of the University Children's Hospital Zurich because of a concussion (diagnosed by medical doctor) Exclusion Criteria: Preterm birth (< 37 gestational weeks) Diagnosed hearing disorder Psychiatric, syndromal, or neurological pre-existing condition (except for previous concussion) Skin disorder/skin problem in the face/ear area that requires Treatment Usage of neuroactive substances Patients: Concomitant injury that requires intense pain medication or a prolonged hospital stay, or that causes limited use of the dominant Hand Patients: Previous moderate-severe TBI Controls: Injury of the dominant hand, on head, arm, or leg Controls: Previous TBI (of any severity) Additional inclusion criteria for the optional MRI measurement for both groups: Age at least 8 years Fulfilment of all MRI safety criteria The participant and the legal representative would want to know about incidental findings. Girls: No pregnancy or breast feeding.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Participants in this group will receive all-night auditory stimulation during sleep over one week using a portable, in-home device (MHSL-SleepBand). | Device: Auditory Stimulation<br>* The device records biosignals and precisely plays tones to enhance sleep slow waves.<br>|
| Sham Comparator: Control group<br>Participants in this group will receive sham-stimulation, i.e. the device will be applied (biosignals will be recorded), but no tones will be played. | Device: Auditory Stimulation<br>* The device records biosignals and precisely plays tones to enhance sleep slow waves.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Performance - attention | Assessed by standardized test (normative values). | Measured one month after study inclusion. | 
| Cognitive Performance - processing speed | Assessed by standardized test (normative values). | Measured one month after study inclusion. | 
| Cognitive Performance - executive function | Assessed by standardized test (normative values). | Measured one month after study inclusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective recovery | Assessed by standardized symptom questionnaires. | Measured at baseline, one week later (intermediate assessment), one month later (follow-up 1) and six months later (follow-up 2). | 
| Algorithm performance | The algorithm flags which are produced by the mobile device used for the auditory stimulation (i.e. sleep detection flags, stimulation flags). They are used to investigate the algorithm performance for each subject. | Recorded during seven nights of stimulation or sham (intervention week). | 
| Neurological outcome | Measured using Magnetic Resonance Imaging (standard structural and hemodynamic imaging, DTI, and susceptibility weighting) to investigate the neurological outcome. | One month after study inclusion (follow-up 1). | 
| Injury characteristics | Only for patients: Injury characteristics collected from the Hospital Information System that might influence baseline and follow-up measures and their change over time. | baseline, pre-intervention | 
| Other possible moderators of the Intervention | For example age and socio-economic status. | Collected at the baseline assessment. | 
| EEG power | Power in frequency bands (delta, theta, alpha, beta, gramma). | Recorded during the intervention week. | 
| Sleep stages | EEG, EOG and EMG used for sleep scoring (sleep stages). | Recorded during the intervention week. | 
| Sleep EEG characteristics | Characteristics of sleep EEG Features (slow waves, spindles). | Recorded during the intervention week. | 
| Subjective sleep | Assessed by standardized questionnaire | Collected throughout the whole study participation, in total 6 months (baseline, one week later (intermediate assessment), one month later (follow-up 1) and six months later (follow-up 2)). | 
| Actigraphy | Measured by GENEActiv (activity bouts). | Recorded during the intervention week. | 
| Objective and subjective sleep measures | Sleep measured by EEG and actigraphy (objective) as well as questionnaires (subjective) | Recorded at all study visits over a period of six months (baseline assessment, intervention week, follow-up 1 and follow-up 2).. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep, auditory stimulation, post-concussive symptoms, in-home EEG