Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP)

October 3, 2024 updated by: Michael Brandon Westover, Massachusetts General Hospital
Sleep deprivation is common and often severe in critically ill patients cared for in intensive care units (ICUs) and is hypothesized to be a modifiable risk factor for delirium, which in turn is hypothesized to be a modifiable risk factor for long-term cognitive disability following recovery from critical illness. Dexmedetomidine (Dex) reduces the incidence of delirium in ICU patients by unknown mechanisms. The Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP) Trial aims to determine whether Dex reduces delirium by improving sleep, whether a low- and/or very-low dose continuous infusion of Dex increases delirium-free days more, and the relationship between sleep deprivation in the ICU to long-term cognitive outcomes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Sleep deprivation is among the most common complaints about the ICU experience. ICU sleep tends to be light and non-restorative (as opposed to deep/restorative sleep), severely fragmented, and distributed throughout the day and night rather than consolidated into nighttime hours. Sleep-deprived patients suffer from sleep debt, a condition of impaired attention and memory, and cognitive slowing. Sleep disturbances in the ICU arise not only from light and noise pollution, but also from drugs that interfere with brain activity involved in restorative sleep. Sleep deprivation has also been suggested as a major modifiable risk factor for acute encephalopathy, also known as delirium. Delirium is an acute state of confusion that affects up to 50% of non-ventilated ICU patients and is one of six leading causes of preventable morbidity and mortality in hospitalized elderly patients. Many patients who survive delirium experience long-term cognitive impairment and loss of independence. Current medications used in the ICU to treat sleep problems (e.g. benzodiazepines, antipsychotics) do not induce natural sleep and do not prevent delirium. In contrast, the investigators have found that the α2-adrenoceptor agonist dexmedetomidine can induce biomimetic sleep, a brain state whose pattern of electroencephalogram (EEG) activity, cerebral blood flow, and functional connectivity approximates restorative sleep. Moreover, a recent large clinical trial in post-surgical patients suggests that low-dose dexmedetomidine given overnight substantially reduces the risk of delirium. It is unknown whether this benefit is linked to improved sleep, or whether patients with better sleep while in the ICU have better long-term cognitive outcomes. The investigator's central hypothesis is that sleep deprivation substantially mediates both the short- and long-term cognitive impairments associated with delirium in critical illness. To test this hypothesis, the ICU-SLEEP trial aims to: 1A) Compare the burden of delirium, as measured by the number of delirium-free days (DFDs), in ICU patients non-ventilated at study enrollment, who are receiving biomimetic sleep induced by Dex, given as a continuous overnight 1) very-low-dose or 2) low-dose infusion vs. 3) usual care and placebo; 1B) Assess whether the 1) very-low-dose continuous overnight infusion of Dex increases DFDs compared to the 2) low-dose continuous overnight infusion; 2A) Determine whether Dex reduces ICU delirium via reducing sleep deprivation, using causal mediation analysis; 2B) Determine the associations between specific components of acute cognitive impairment, seen in sleep deprivation and delirium, with specific measures of sleep deprivation; 3A) Determine whether ICU patients treated with Dex while in the hospital have a lower incidence of long-term cognitive impairment; 3B) Determine whether any differences in long-term cognitive impairment between ICU survivors treated with Dex vs. usual care and placebo are mediated by differences in sleep deprivation. The knowledge gained will provide insights into the mechanisms by which Dex prevents delirium and guidance on the optimal dosing strategy for prophylactic Dex, which can be used to design pivotal phase 3 clinical trials.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
522

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Admitted or scheduled to be admitted to an MGH medical or surgical ICU (Blake 7 or 12, or Ellison 4)
  2. Male or female, aged ≥ 50 years
  3. Provision of signed and dated informed consent form (by patient or legally authorized representative (LAR))
  4. Stated willingness to comply with all study procedures and availability for the duration of the study
  5. Not on mechanical ventilation at the time of enrollment
  6. Able to be enrolled before 7PM
  7. For females of reproductive potential: pregnancy test is negative

Exclusion Criteria

  1. Dementia, as measured by a score of ≥3.3 on the Informant Questionnaire on Cognitive Decline in the Elderly Short Form (IQCODE-SF)
  2. Unable to be assessed for delirium (e.g. blindness or deafness)
  3. Follow-up would be difficult (e.g. active substance abuse, homelessness)
  4. Pregnancy or lactation
  5. Known pre-existing neurologic disease or injury with focal neurologic or cognitive deficits
  6. Serious cardiac disease (e.g. sick sinus syndrome without a pacemaker, sinus bradycardia, second- or third-degree AV block, congestive heart failure with ejection fraction <30%)
  7. Severe liver dysfunction (Child-Pugh class C)
  8. Severe renal dysfunction (receiving dialysis)
  9. Low likelihood of survival >24 hours
  10. Low likelihood of staying in ICU overnight
  11. Known allergic reactions to components of dexmedetomidine
  12. Patient is receiving or planning to go on dexmedetomidine at the time of enrollment
  13. Patient is receiving either of the anticholinergic drugs scopolamine or penehyclidine; or alpha-2-agonist clonidine
  14. Concomitant enrollment in another study protocol that may interfere with data acquisition or reliability of measurements
  15. Deemed unsuitable for selection by the research team or ICU providers due to any medical, legal, social, language (non-English speaking) or interpersonal issues that would either compromise the study or the routine care of patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Dexmedetomidine, continuous very-low-dose overnight infusion
Patients randomized to this study arm will receive dexmedetomidine, given as a very-low-dose (0.1 mcg/kg/hour group; rate of 0.075 mL/kg/hour at a concentration of 1.33 mcg/mL) continuous overnight infusion. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first.
Drug: Dexmedetomidine
"Dex (Precedex, Dexmedetomidine HCl Injection) is produced by Pfizer Inc, NY, Ny (formerly Hospira). Dex is a white or almost white powder that is freely soluble in water and has a pKa of 7.1. Its partition coefficient in-octanol: water at pH 7.4 is 2.89. Dex is supplied as a clear, colorless, isotonic solution with a pH of 4.5 to 7.0. Each mL contains 118 mcg of dexmedetomidine hydrochloride equivalent to 100 mcg (0.1mg) of dexmedetomidine and 9 mg of sodium chloride in water. The solution is preservative-free and contains no additives or chemical stabilizers. The MGH Pharmacy currently obtains Dex from the supplier as a solution in 50 mL clear-glass bottles, as a clear liquid, at a concentration of 4mcg/mL."
Other Names:
  • Precedex (dexmedetomidine hydrochloride; Pfizer Inc, NY, Ny)
Active Comparator: Dexmedetomidine, continuous low-dose overnight infusion
Patients randomized to this study arm will receive dexmedetomidine, given as a low-dose (0.3 mcg/kg/hour group; rate of 0.075 mL/kg/hour at a concentration of 4 mcg/mL) continuous overnight infusion. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first.
Drug: Dexmedetomidine
"Dex (Precedex, Dexmedetomidine HCl Injection) is produced by Pfizer Inc, NY, Ny (formerly Hospira). Dex is a white or almost white powder that is freely soluble in water and has a pKa of 7.1. Its partition coefficient in-octanol: water at pH 7.4 is 2.89. Dex is supplied as a clear, colorless, isotonic solution with a pH of 4.5 to 7.0. Each mL contains 118 mcg of dexmedetomidine hydrochloride equivalent to 100 mcg (0.1mg) of dexmedetomidine and 9 mg of sodium chloride in water. The solution is preservative-free and contains no additives or chemical stabilizers. The MGH Pharmacy currently obtains Dex from the supplier as a solution in 50 mL clear-glass bottles, as a clear liquid, at a concentration of 4mcg/mL."
Other Names:
  • Precedex (dexmedetomidine hydrochloride; Pfizer Inc, NY, Ny)
Placebo Comparator: Usual care and placebo (normal saline)
Patients randomized to this study arm will receive standard ICU care plus a normal saline placebo, given as a continuous overnight infusion, at a rate of 0.075 mL/kg/hour. Study drug will be provided by the MGH research pharmacy as a clear liquid and delivered by the research staff directly to the patient's ICU nurse, in a 60 mL syringe/bag (s). Nursing will then administer the study drug intravenously each night (11 hours; 8PM through 7AM) until either discharge from the ICU or up to 7 consecutive nights, whichever occurs first.
Drug: Placebo
From the package insert: "0.9% Sodium Chloride Injection, USP is sterile and nonpyrogenic. It is produced by Pfizer Inc, NY, Ny (formerly Hospira). It is a parenteral solution containing sodium chloride in water for injection intended for intravenous administration. Each 100 mL of 0.9% Sodium Chloride Injection, USP contains 900 mg sodium chloride in water for injection. Electrolytes per 1000 mL: sodium (Na+ ) 154 mEq; chloride (Cl- ) 154 mEq. The osmolarity is 308 mOsmol/L (calc.). The pH is 5.6 (4.5 to 7.0). This solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only as a single-dose injection. When smaller doses are required, the unused portion should be discarded. 0.9% Sodium Chloride Injection, USP is a parenteral fluid and electrolyte replenisher. Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water. Water for Injection, USP is chemically designated H2O."
Other Names:
  • Normal saline (0.9% Sodium Chloride; Pfizer Inc, NY, Ny)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
In-hospital Delirium-free days (IH-DFDs)
Time Frame: First 14 hospital days from start of infusion [or until hospital discharge, whichever occurs first]
In-hospital Delirium-free days (IH-DFDs) are calculated as the sum of days without delirium during the first 14 hospital days from start of infusion in the two Dex treatment arms combined (arms 1 and 2) vs. usual care (arm 3). Delirium is defined as any positive Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU) assessment, with each yielding a binary result (1 = delirious/CAM+, 0 = non-delirious/CAM-). For each patient, delirium is assessed twice daily. If a patient has any positive delirium assessments on any given day of the assessment days, they are considered to have had delirium during these days. Days with coma are counted together with delirium.
First 14 hospital days from start of infusion [or until hospital discharge, whichever occurs first]

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
ICU-Delirium-free days (ICU-DFDs)
Time Frame: First 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
ICU-Delirium-free days (ICU-DFDs) are calculated as the sum of days without delirium during the first 7 ICU days from start of infusion in the two Dex treatment arms combined (arms 1 and 2) vs. usual care (arm 3). Delirium is defined as any positive Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU) assessment, with each yielding a binary result (1 = delirious/CAM+, 0 = non-delirious/CAM-). For each patient, delirium is assessed twice daily. If a patient has any positive delirium assessments on any given day of the assessment days, they are considered to have had delirium during these days. Days with coma are counted together with delirium.
First 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Sleep Quantity-quality (SQ) score
Time Frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
The Sleep Quantity-quality (SQ) score is a sleep composite measure formed by averaging the z-scores for raw measures of sleep quality (total sleep time (TST), sleep fragmentation index (SFI), time in N2, time in N3), where a higher SQ score indicates better outcomes.
First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Acute Cognitive Function (ACF) score
Time Frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
The Acute Cognitive Function (ACF) score is a reliable change index controlling for practice effects (RCI+PE) for a composite of acute cognitive measures. These include twice daily Confusion Assessment Method-Severity (CAM-S; Short Form (0-7) & Long Form (0-19), where higher scores indicate increased severity of delirium symptoms); and Psychomotor Vigilance Test (PVT) scores collected in the first 7 ICU days from start of infusion [or until ICU discharge, whichever occurs first]. Composites will be formed by averaging z-scores for CAM-S and PVT scores, where a higher ACF score indicates better outcomes.
First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Long-term Cognitive Function (LCF) score
Time Frame: 3-, 6-, and 12 months post-enrollment
The Long-term Cognitive Function (LCF) score is a composite average of z-scores from long-term cognitive outcome measures of the different components, where a higher LCF score indicates better outcomes.
3-, 6-, and 12 months post-enrollment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Spearman correlation coefficient (rho) between sleep quality and acute cognitive function
Time Frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Spearman's correlation coefficient (rho) describes the correlation between sleep quality on the previous night, as measured by the Sleep Quantity-quality (SQ) score, and acute cognitive function, as measured by the Acute Cognitive Function (ACF) score.
First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Average Causal Mediation Effect (ACME) of sleep deprivation on delirium-free days
Time Frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Causal effect of sleep deprivation (SD) on In-hospital Delirium-free days (IH-DFDs) and ICU-Delirium-free days (ICU-DFDs), where SD is quantified by the Sleep Quantity-quality (SQ) score.
First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Average Causal Mediation Effect (ACME) of sleep deprivation on acute cognitive outcomes
Time Frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Causal effect of sleep deprivation (SD) on acute cognitive outcomes, where SD is quantified by the Sleep Quantity-quality (SQ) score, and acute cognitive function is quantified by the Acute Cognitive Function (ACF) score.
First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]
Average Causal Mediation Effect (ACME) of sleep deprivation on long-term cognitive outcomes
Time Frame: First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]; 3-, 6-, and 12 months post-enrollment
Causal effect of sleep deprivation (SD) on long-term cognitive outcomes, where SD is quantified by the Sleep Quantity-quality (SQ) score, and long-term cognitive function is quantified by the Long-term Cognitive Function (LCF) score.
First 14 ICU days from start of infusion [or until ICU discharge, whichever occurs first]; 3-, 6-, and 12 months post-enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: M. Brandon Westover, MD, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 29, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 5, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 24, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017P000090
  • R01NS102190 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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