The Effect of Sodium Oxybate on Sleep Architecture

The Effect of Sodium Oxybate on Sleep Architecture in Critically Ill Patients: A Double-Blind, Crossover Pilot Study

The purpose of this study is to determine what effect sodium oxybate has on the functions of sleep in mechanically ventilated, critically ill patients hospitalized in an intensive care unit.

Study Overview

• Status: Withdrawn
• Conditions: Mechanically Ventilated ICU Patients
• Intervention / Treatment: Drug: sodium oxybate; Drug: placebo

Detailed Description

Sleep is disrupted in the critically ill and may lead to impaired neurocognitive function, decreased immune function, increased protein catabolism, and may compromise the ability to wean patients from mechanical ventilation. Critically ill patients may appear to sleep throughout most of their stay, but their quality of sleep is different from that of a normal healthy subject.Critically ill patients spend more time in the wakefulness stages of sleep (Stage 1 and 2) at the expense of the restorative stages (Stage 3 and 4) and REM sleep. These patients also experience an increased number of arousals and awakenings. Various factors are thought to be the cause of abnormal sleep architecture: ICU environment, pain, illness severity, psychosocial stress, medications, and mechanical ventilation.

Sodium oxybate (Xyrem®) is the sodium salt of the central nervous system depressant γ-hydroxybutyric acid (GHB) and is currently approved for use in narcoleptic patients to improve cataplexy and excessive daytime sleepiness.

Studies evaluating the use of sodium oxybate in narcoleptic patients suggest that sodium oxybate is effective at increasing slow-wave sleep, sleep efficiency, sleep latency, and REM-sleep efficiency, while also decreasing REM-sleep latency, stage 1 NREM sleep and sleep fragmentation.3, 16-19 Currently there is a lack of data evaluating the effects of sodium oxybate on sleep in critically ill patients. Obtaining evidence that sodium oxybate improves sleep architecture in the critically ill, may provide the foundation to complete future studies evaluating the effect of sodium oxybate on clinical outcomes such as duration of mechanical ventilation and length of ICU stay. Based on sodium oxybate's ability to improve sleep architecture in narcoleptic patients along with the fact that critically ill patients have similar disrupted sleep architecture, it's postulated that sodium oxybate may improve the sleep architecture in critically ill patients.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Mechanically ventilated ≥ 24º on an AC mode
• Placement of enteral or gastric tube (Note: these tubes will not be placed exclusively for the purposes of the study.)
• Tolerating enteral nutrition via either the stomach or small intestine (≥20mL/hr for ≥ 12 hours)

Exclusion Criteria:

• Anticipated duration of mechanical ventilation ≤72º (as per MICU team estimate)
• Riker SAS ≤ 2 (as determined by patient's nurse and/or study investigator)
• History of irreversible brain disease consistent with severe dementia based on MICU service admission note
• Admitted with a primary neurological condition (e.g. intracranial hemorrhage)
• History of seizure disorder or intracranial surgery
• History of myocardial infarction in prior 6 months
• Pregnancy (all women of child bearing potential will undergo a serum pregnancy test prior to study consent)
• Administration of a scheduled benzodiazepine as either a continuous drip or given by IVP
• Acute alcohol withdrawal
• AST/ALT >2 times ULN, INR >2 or T bilirubin > 1.5
• Current or prior use of sodium oxybate in the -past 30 days.
• Hypernatremia with a serum sodium >150
• Current use of the following hypnotics: barbiturates, melatonin, zolpidem, eszopiclone, or zaleplon
• Use of neuromuscular blocking agents
• Allergy to sodium oxybate
• Known succinic semialdehyde dehydrogenase deficiency
• History of periodic limb movement disorder.
• A prognosis considered to be hopeless (as per MICU team)
• Inability to obtain informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Active drug	Drug: sodium oxybate; The dose of sodium oxybate will be 4.5g every 4 hours x 2 doses. The first dose of study medication will be given at 10pm followed by the next dose four hours later and crossed over the next day; Other Names: XYREM
Placebo Comparator: P; Placebo drug	Drug: placebo; The dose of placebo sodium oxybate will be 4.5g every 4 hours x 2 doses. The first dose of study medication will be given at 10pm followed by the next dose four hours later and then crossed over the next day; Other Names: Xyrem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To gain a better understanding of the effect of sodium oxybate on the following components of sleep architecture: % time in sleep stage and arousals and awakenings	72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
To observe any short-term adverse effects of sodium oxybate in mechanically ventilated ICU patients	72 hours

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Investigators: Principal Investigator: Carolyn D'Ambrosio, MD, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: August 29, 2008
• First Submitted That Met QC Criteria: August 29, 2008
• First Posted (Estimate): September 1, 2008

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: mechanical ventilation; sleep; critically ill
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adjuvants, Anesthesia; Sodium Oxybate
• Other Study ID Numbers: NEMC-8479