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Providing "Good Sleep" for ICU Sedation (ASRV)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Masimo Labs
Information provided by (Responsible Party):
Mervyn Maze, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01342328
First received: December 7, 2010
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

Cognitive dysfunction, either alone or as an element in the syndrome of delirium, is a common occurrence with an incidence as high as 75% in intensive care unit (ICU) patients and can independently result in serious consequences including higher mortality rate. Delirium develops through a complex interaction between the patient's baseline vulnerability (risk factors) and precipitating factors such as disruption of sleep that may occur during hospitalization. While sedative-hypnotic agents that are used to facilitate hypnosis and the management of mechanically ventilated patients converge on the neural substrate that mediate endogenous sleep, they do so at different juncture points depending on its molecular mechanism of hypnotic action. Hypnotic agents that modulate the GABAA receptor converge at the level of the hypothalamus while α2 adrenergic agonists converge on sleep pathways within the brainstem. This translational project seeks to determine whether sedation mediated by activation of α2 adrenoceptors (dexmedetomidine) is more like natural sleep than that provided by a sedative agent that modulates the GABAA receptor (propofol). The investigators will examine volunteers who will be monitored continuously by electroencephalography (EEG) and whole-brain functional connectivity by magnetoencephalography (MEG) during each of three sleep stages, namely, that induced by dexmedetomidine, propofol, or saline (natural sleep, control). The two drug-induced sleep regimens will be compared to natural sleep using EEG and brain connectivity by MEG


Condition Intervention
Sleep Disorders
Other: Normal saline infusion
Drug: Dexmedetomidine
Drug: Propofol

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Providing "Good Sleep" for ICU Sedation

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Compare the electroencephalography features of sleep produced by three sleep-induced regimens [ Time Frame: Data will be collected during patient's sleep, which will last 4hours. ] [ Designated as safety issue: No ]
    The investigators will evaluate the "power" in the delta rhythm range and amount of slow-wave-sleep

  • Compare the magnetoencephalography features of sleep produced by three sleep induced regimens [ Time Frame: Data will be collected during patient's sleep, which will last 4hours. ] [ Designated as safety issue: No ]
    The investigators will evaluate the magnetoencephalography-defined brain connectivity


Estimated Enrollment: 10
Study Start Date: May 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
For this arm, the volunteer subject will receive a saline infusion during the sleep session.
Other: Normal saline infusion
Normal saline infusion
Experimental: Dexmedetomidine (DEX)
For this arm, the volunteer subject will receive a DEX infusion for sedation during the sleep session.
Drug: Dexmedetomidine

Infusion of Dexmedetomidine will be administrated during the overnight sleep study. An initial target concentration of 0.25 ng/ml will be selected. After 5 min, the sedative point will be assessed and the concentration will be adjusted stepwise by increments and decrements of 0.05 ng/ml. This process will be repeated until the target sedative state is achieved. Using the Richmond Agitation Sedation Scale (RASS) infusion rates, using known pharmacokinetic parameters will be adjusted to achieve equivalent levels of sedation (RASS -3) for both DEX and propofol sessions.

We aim to achieve an RASS of -3 so that the subjects are "moderately sedated". This state of sedation will be maintained for 3-4 hours.

Other Names:
  • Precedex
  • DEX
Experimental: Propofol
For this arm, the volunteer subject will receive a propofol infusion for sedation during the sleep session.
Drug: Propofol

For propofol, an initial concentration of 0.75 ng/ml will be targeted. Depending on the score achieved, the infusion rate will be increased or decreased every 5 min by 0.2 ng/ml until the target sedative state is achieved.

Note that the target sedative state (RASS score of -3) is the same for both DEX and propofol sessions, with the investigator being unaware of which drug is being administered. To ensure the investigator is not aware of the type of drug being administered, all drug delivery systems will be covered.

Intravenous drug delivery will be continued throughout the scanning period for 3-4 hours to maintain equivalent levels of sedation for both DEX and propofol.

Other Name: Diprivan

Detailed Description:

In this proposal the investigators seek to determine whether sedation mediated by activation of α2 adrenoceptors (dexmedetomidine) is more like natural sleep than that provided by a sedative agent that modulates the GABAA receptor (propofol), two common widely used sedative agents in ICU. Ten volunteers will be enrolled and each subject will be studied on three experimental sessions. Subjects will be randomized to receive a continuous infusion of either saline, dexmedetomidine (DEX), or propofol in each of the three sessions. By relying on clinical rating scales, the investigators ensure that the doses of DEX and propofol administered induce equisedative states before progressing to magnetoencephalography and electroencephalography data collection.

If the restorative and reparative benefits of sleep mitigate the development of cognitive dysfunction, this will result in shorter ICU length of stay for critically ill patients with a concomitant reduction in healthcare costs. Furthermore, it is possible that the restorative properties of sleep for the central nervous system can extend to the immune system with less infection and/or greater likelihood of survival from sepsis.

In this manner, our project will translate experimental data towards clinical practice and the adoption of rational and clinically supported interventions in the ICU that are likely to improve not only patient reported outcome measures, but also the chance of surviving critical illness.

Each experimental session will take a maximum of 7 hours (5 hours maximum for control sessions).

Sessions have to be separated by at least one week. Subjects will be enrolled for a minimum of 3 weeks (1 session on each week) and no more than 3 months.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Volunteer agreement and written informed consent
  • Healthy female or male between 18 and 45 years of age
  • Body Mass Index < 30 kg/m2
  • Non-pregnant and non-lactating
  • Normal airway anatomy (Mallampati class I)

Exclusion Criteria:

  • Subject has a history of recent alcohol or drug abuse
  • Subject is unable to communicate in English
  • Subject is unwilling to meet fast guidelines (fast light meal or non-human milk for at least 8 hours, and clear liquids at least for 2 hours prior to induction of sedation on the day of the study)
  • Subject has taken caffeine containing beverages less than 8 hours before study begins
  • Subject is not able to avoid sleep for a minimum of 16 hours prior to testing
  • Subject has a known allergy to either of the sedative-hypnotic drugs to be used in the study
  • Subject has abnormal airway anatomy, including loose teeth
  • Subject has any family history of complications from anesthesia
  • Subject has history of sleep apnea
  • Subject has any reported illness, upper respiratory tract infection, abnormal vital signs, or concerning findings on the physical exam for the past 6 weeks
  • Subject has a positive urine pregnancy test
  • Subject is unable to sleep supine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01342328

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Masimo Labs
Investigators
Principal Investigator: Mervyn Maze, MB, ChB University of California, San Francisco
  More Information

No publications provided

Responsible Party: Mervyn Maze, MD, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01342328     History of Changes
Other Study ID Numbers: 10-03906
Study First Received: December 7, 2010
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Sleep disruption
Sleep hygiene
Sedative agents and sleep
Electroencephalography
REM sleep
Magnetoencephalography

Additional relevant MeSH terms:
Parasomnias
Sleep Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Dexmedetomidine
Propofol
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014