The Effect of Sodium Oxybate on Sleep Architecture

This study has been withdrawn prior to enrollment.
(Sponsor pulled funding secondary to economy issues)
Sponsor:
Information provided by:
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT00744393
First received: August 29, 2008
Last updated: September 4, 2009
Last verified: September 2009

August 29, 2008
September 4, 2009
October 2008
December 2009   (final data collection date for primary outcome 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 [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00744393 on ClinicalTrials.gov Archive Site
To observe any short-term adverse effects of sodium oxybate in mechanically ventilated ICU patients [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Mechanically Ventilated ICU Patients
  • 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 Name: XYREM
  • 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 Name: Xyrem
  • Active Comparator: A
    Active drug
    Intervention: Drug: sodium oxybate
  • Placebo Comparator: P
    Placebo drug
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
10
December 2009
December 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00744393
NEMC-8479
No
Carolyn D'Ambrosio, MD, Tufts-NEMC
Tufts Medical Center
Not Provided
Principal Investigator: Carolyn D'Ambrosio, MD Tufts Medical Center
Tufts Medical Center
September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP