Closed Loop Acoustic Stimulation During Sedation With Dexmedetomidine

Study Overview
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Brief Summary
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Prospective within-subject study of dexmedetomidine sedation paired with CLAS conditions in repeated blocks. Intervention will consist of CLAS in-phase with EEG slow waves. Anti-phase stimulation will serve as an active control while sham stimulation will serve as a passive control.

Detailed Description
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Both nonpharmacologic and pharmacologic interventions augment expression of EEG slow waves that mimic those of natural sleep. Closed loop auditory stimulation (CLAS) is a noninvasive inexpensive approach to augment the spectral power and duration of these slow waves. Whether in-phase CLAS may address this need is unknown, since acoustic potentiation of pharmacologically-induced slow waves has not been investigated. This prospective within-subject study of dexmedetomidine sedation paired with CLAS will assess the feasibility of augmenting EEG slow waves during sedation.

Official Title
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Closed Loop Acoustic Stimulation During Sedation With Dexmedetomidine

Conditions
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Sleep, Sedation Complication

Intervention / Treatment
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* Radiation: MRI
* Diagnostic Test: Quantitative Sensory Testing (QST)
* Diagnostic Test: Home sleep study
* Other: Acoustic stimulation (65db) up-slope of EEG with QST
* Other: Acoustic stimulation (65db) down-slope of EEG with QST
* Other: 0 db with QST
* Drug: Dexmedetomidine
* Other: Breathe-Squeeze Task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-40 years Healthy volunteers (American Society of Anesthesiologists Physical Status 1-2). Exclusion Criteria: Diagnosed sleep disorders Habitually short sleepers Diagnosed psychiatric disorders Use of psychoactive medication (e.g., antidepressants, mood stabilizers or antipsychotics), diagnosed hearing disorder Neck circumference > 40 cm Body Mass Index > 30 Acknowledged recreational drug or nicotine use Resting heart rate during slow wave sleep < 40 beats per minute Pregnancy or nursing Persistently inconsistent or elevated QST heat pain tolerance thresholds (>50 ºC).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLASS-D Cohort<br>Within-subject crossover cohort with intervention, acoustic stimulation delivered in phase with the anticipated trough of EEG slow wave oscillation, and 0 dB stimulation. | Radiation: MRI<br>* A non-contrast brain MRI will be acquired for localizing EEG slow waves<br>* Other names: Structural magnetic resonance imaging;Diagnostic Test: Quantitative Sensory Testing (QST)<br>* Quantitative sensory testing (QST) using increasing ramp thermal stimulation (32-52 ºC) will be delivered to compare arousal thresholds between conditions.<br>* Other names: Quantitative Sensory Testing;Diagnostic Test: Home sleep study<br>* Unattended home sleep studies will be conducted on the night preceding sedation and on the night following sedation to assess changes in slow wave homeostasis.<br>* Other names: Unattended polysomnography;Other: Acoustic stimulation (65db) up-slope of EEG with QST<br>* Acoustic stimulation (65 db) synchronized in-phase with the up-slope of EEG slow waves<br>* Other names: In-phase CLAS with sensory testing;Other: Acoustic stimulation (65db) down-slope of EEG with QST<br>* 65 dB acoustic stimulation synchronized with the down-slope of the EEG slow waves (anti-phase)<br>* Other names: Anti-phase CLAS with sensory testing;Other: 0 db with QST<br>* sham stimulation (0 dB volume)<br>* Other names: Sham CLAS with sensory testing;Drug: Dexmedetomidine<br>* All participants will receive dexmedetomidine with sedation titrated step-wise to 2, 3 or 4 ng/ml<br>* Other names: Dexmedetomidine hydrochloride;Other: Breathe-Squeeze Task<br>* All participants will be asked to perform the breathe-squeeze task throughout the experiment. This will allow us to determine loss and return of responsiveness.<br>* Other names: Internally directed behavioral task;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in EEG slow wave amplitude from sham to in-phase stimulation | EEG slow waves amplitude relative to the timing of the stimulation | up to 3 months after consent | 
| Difference in EEG slow wave duration from sham to in-phase stimulation | EEG slow waves duration relative to the timing of the stimulation | up to 3 months after consent | 
| Difference in EEG slow wave amplitude from anti-phase to in-phase stimulation | EEG slow waves amplitude relative to the timing of the stimulation | up to 3 months after consent | 
| Difference in EEG slow wave duration from anti-phase to in-phase stimulation | EEG slow waves duration relative to the timing of the stimulation | up to 3 months after consent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of reactivity to thermal stimulation from anti-phase to in-phase stimulation | Threshold for responsiveness to thermal stimulation | up to 3 months after consent | 
| Difference of reactivity to thermal stimulation from sham to in-phase stimulation | Threshold for responsiveness to thermal stimulation | up to 3 months after consent | 
| Change in slow wave activity on the night of the intervention will be compared to that on the night prior to the study session. | Slow wave activity calculated during N3 sleep | up to 3 months after consent | 
| Localization of slow waves | Brain regions with localization of EEG slow waves during dexmedetomidine sedation | up to 3 months after consent |