Clinical trial NCT00744393: The Effect of Sodium Oxybate on Sleep Architecture
Official title: The Effect of Sodium Oxybate on Sleep Architecture in Critically Ill Patients: A Double-Blind, Crossover Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Mechanically Ventilated ICU Patients
Keywords: sleep
critically ill
mechanical ventilation
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2008-09-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 72 hours
Secondary outcomes:
measure: To observe any short-term adverse effects of sodium oxybate in mechanically ventilated ICU patients
timeFrame: 72 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Carolyn D'Ambrosio, MD
role: PRINCIPAL_INVESTIGATOR
References: