Closed Loop Acoustic Stimulation During Sedation With Dexmedetomidine (CLASS-D)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sleep; Sedation Complication
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine/Barnes-Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: CLASS-D Cohort; 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; A non-contrast brain MRI will be acquired for localizing EEG slow waves; Other Names: Structural magnetic resonance imaging; Diagnostic test: Quantitative Sensory Testing (QST); Quantitative sensory testing (QST) using increasing ramp thermal stimulation (32-52 ºC) will be delivered to compare arousal thresholds between conditions.; Other Names: Quantitative Sensory Testing; Diagnostic test: Home sleep study; 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.; Other Names: Unattended polysomnography; Other: Acoustic stimulation (65db) up-slope of EEG with QST; Acoustic stimulation (65 db) synchronized in-phase with the up-slope of EEG slow waves; Other Names: In-phase CLAS with sensory testing; Other: Acoustic stimulation (65db) down-slope of EEG with QST; 65 dB acoustic stimulation synchronized with the down-slope of the EEG slow waves (anti-phase); Other Names: Anti-phase CLAS with sensory testing; Other: 0 db with QST; sham stimulation (0 dB volume); Other Names: Sham CLAS with sensory testing; Drug: Dexmedetomidine; All participants will receive dexmedetomidine with sedation titrated step-wise to 2, 3 or 4 ng/ml; Other Names: Dexmedetomidine hydrochloride; Other: Breathe-Squeeze Task; 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.; Other Names: Internally directed behavioral task

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Ben J Palanca, MD PhD, Washington University School of Medicine

Publications and helpful links

General Publications

• Prerau MJ, Brown RE, Bianchi MT, Ellenbogen JM, Purdon PL. Sleep Neurophysiological Dynamics Through the Lens of Multitaper Spectral Analysis. Physiology (Bethesda). 2017 Jan;32(1):60-92. doi: 10.1152/physiol.00062.2015.
• Leger D, Debellemaniere E, Rabat A, Bayon V, Benchenane K, Chennaoui M. Slow-wave sleep: From the cell to the clinic. Sleep Med Rev. 2018 Oct;41:113-132. doi: 10.1016/j.smrv.2018.01.008. Epub 2018 Feb 5.
• Neske GT. The Slow Oscillation in Cortical and Thalamic Networks: Mechanisms and Functions. Front Neural Circuits. 2016 Jan 14;9:88. doi: 10.3389/fncir.2015.00088. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 20, 2021
• Primary Completion (ACTUAL): June 1, 2022
• Study Completion (ANTICIPATED): July 1, 2023

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (ACTUAL): December 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 201907086

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes