Sleep, Sedation Complication
Conditions
Brief summary
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
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.
Interventions
RADIATIONMRI
A non-contrast brain MRI will be acquired for localizing EEG slow waves
DIAGNOSTIC_TESTQuantitative Sensory Testing (QST)
Quantitative sensory testing (QST) using increasing ramp thermal stimulation (32-52 ºC) will be delivered to compare arousal thresholds between conditions.
DIAGNOSTIC_TESTHome 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.
OTHERAcoustic stimulation (65 decibels or db) up-slope of EEG with QST
Acoustic stimulation (65 db) synchronized in-phase with the up-slope of EEG slow waves
OTHERAcoustic stimulation (65db) down-slope of EEG with QST
65 dB acoustic stimulation synchronized with the down-slope of the EEG slow waves (anti-phase)
OTHER0 db with QST
sham stimulation (0 dB volume)
DRUGDexmedetomidine
All participants will receive dexmedetomidine with sedation titrated step-wise to 2, 3 or 4 ng/ml
OTHERBreathe-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.
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in EEG Slow Wave Activity From Sham to In-phase Stimulation | Sham stimulation and in-phase stimulation blocks during the intervention | EEG slow waves activity (power) relative to the timing of the stimulation. Values are log-transformed All participants serve in the same arm but experience both sham and in-phase blocks. |
| Difference in EEG Slow Wave Activity From Anti-phase to In-phase Stimulation | Anti-phase and in-phase blocks during the intervention | EEG slow waves activity (power) relative to the timing of the stimulation. Values are log-transformed All participants serve in the same arm but experience both anti-phase and in-phase blocks. |
| Difference in EEG Slow Wave Density From Anti-phase to In-phase Stimulation | anti-phase and in-phase blocks during the intervention | Difference in EEG slow wave density from anti-phase to in-phase stimulation by looking at EEG slow waves duration relative to the timing of the stimulation All participants serve in the same arm but experience both anti-phase and in-phase blocks. |
| Difference in EEG Slow Wave Density From Sham to In-phase Stimulation | Sham stimulation and in-phase stimulation blocks during the intervention | Difference in EEG slow wave density from sham to in-phase stimulation by looking at EEG slow waves relative to the timing of the stimulation All participants serve in the same arm but experience both sham and in-phase blocks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference of Reactivity to Thermal Stimulation From Anti-phase to In-phase Stimulation | Anti-phase and in-phase blocks of the intervention | Difference of reactivity to thermal stimulation from anti-phase to in-phase stimulation by measuring the threshold for responsiveness to thermal stimulation All participants serve in the same arm but experience both anti-phase and in-phase blocks. |
| Difference of Reactivity to Thermal Stimulation From Sham to In-phase Stimulation | Sham and in-phase blocks during intervention | Difference of reactivity to thermal stimulation from sham to in-phase stimulation by measuring the threshold for responsiveness to thermal stimulation All participants serve in the same arm but experience both sham and in-phase blocks. |
| Slow Wave Activity Calculated During N3 Sleep | on the nights before and the night of the intervention | Change in slow wave activity on the night of the intervention will be compared to that on the night prior to the study session. Calculated as power |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBen J Palanca, MD PhD
Washington University School of Medicine
Participant flow
Recruitment details
2 participants were withdrawn after consent.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| ASA Physical Status ASA 1 | 14 Participants |
| ASA Physical Status ASA 2 | 0 Participants |
| ASA Physical Status ASA 3 | 0 Participants |
| ASA Physical Status ASA 4 | 0 Participants |
| ASA Physical Status ASA 5 | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 0 / 16 | 4 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
None listed