The Effect of Sodium Oxybate on Sleep Architecture

Mechanically Ventilated ICU Patients Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00744393
• Other study ID #: NEMC-8479
• Status: Withdrawn
• Phase: Phase 2
• First received: August 29, 2008
• Last updated: February 21, 2018
• Start date: October 2008
• Est. completion date: December 2009

Study information

• Verified date: February 2018
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mechanically Ventilated ICU Patients

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tufts Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To observe any short-term adverse effects of sodium oxybate in mechanically ventilated ICU patients		72 hours