Investigation of Sleep in the Intensive Care Unit

Sleep Clinical Trial

— ICU-SLEEP  

Official title:

Investigation of Sleep in the Intensive Care Unit

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03355053
• Other study ID #: 2017P000090
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2018
• Est. completion date: April 1, 2023

Study information

• Verified date: March 2021
• Source: Massachusetts General Hospital
• Contact: M Brandon Westover, MD/PhD
• Phone: 617-726-3311
• Email: mwestover[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sleep deprivation is common and severe in critically ill patients cared for in intensive care units (ICUs), and is hypothesized to be a key modifiable risk factor for delirium and long-term cognitive disability. Dexmedetomidine reduces the incidence of delirium in ICU patients by unknown mechanisms. This project will determine whether dexmedetomidine reduces delirium by improving sleep, whether bolus dosing vs continuous infusion is better, and the relationship of sleep quality to long-term cognitive outcomes.

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 factors for acute encephalopathy, also known as delirium. Delirium is an acute state of confusion that affects up to 80% of 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, this study is designed to systematically determine 1) the impact of prophylactic dexmedetomidine on sleep quality, 2) the optimal way to give dexmedetomidine (all night vs at the beginning of the night only), 2) the impact of sleep deprivation on short-term cognitive function and delirium, and 3) the contribution of sleep deprivation to long-term neuropsychiatric outcome following critical illness. At the conclusion of these studies, the investigators will have expanded knowledge of sleep physiology in critical illness and relationship of sleep with delirium; evaluated a new preemptive therapeutic strategy to promote sleep and prevent delirium, and developed an understanding of how sleep impacts neuropsychological outcomes after critical illness. These studies will thus will provide crucial guidance for individualized approaches to preserving long-term brain health in this vulnerable patient population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: April 1, 2023
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Admitted to MGH Blake 7 or 12, or Elllison 4 ICU at Massachusetts General Hospital.

2. Male or female, aged > 50 years

3. Provision of signed and dated informed consent form (by patient or 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:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Unable to be assessed for delirium (e.g. blindness or deafness)

2. Pregnancy or lactation

3. Known allergic reactions to components of dexmedetomidine

4. Follow-up would be difficult (e.g. active substance abuse, homelessness)

5. Severe dementia, as measured by a score of =3.3 on the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)

6. Known pre-existing neurologic disease or injury with focal neurologic or cognitive deficits

7. Serious cardiac disease (e.g. sick sinus syndrome, sinus bradycardia, second or third degree AV block, congestive heart failure with ejection fraction < 30%)

8. Severe liver dysfunction (Child-Pugh class C)

9. Severe renal dysfunction (receiving dialysis)

10. Low likelihood of survival >24 hours

11. Low likelihood of staying in ICU overnight

12. Patient is receiving either of the anticholinergic drugs scopolamine or penehyclidine

13. Concomitant enrollment in another study protocol that may interfere with data acquisition or reliability of measurements;

14. 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.

Related Conditions & MeSH terms

• Delirium
• Sleep

Intervention

Drug:
• Dexmedetomidine
See description of study arms

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of delirium	incidence of delirium, defined as any positive CAM or CAM-ICU assessment over the first 7 ICU days (Aim 1a), comparing usual care+placebo (n=250) with Dex (combined slow-bolus + low-dose overnight continuous infusion groups, n=500)	7 days
Secondary	Incidence of delirium between Dex groups	Incidence of delirium within the two Dex treatment subgroups within the first 7 days within the ICU, assessed by the Confusion Assessment Method (CAM) or CAM-ICU.	7 days