Sodium Oxybate in Schizophrenia With Insomnia

This study has been completed.
Sponsor:
Collaborator:
Jazz Pharmaceuticals
Information provided by:
Nathan Kline Institute for Psychiatric Research
ClinicalTrials.gov Identifier:
NCT00594256
First received: January 3, 2008
Last updated: November 30, 2009
Last verified: November 2009

January 3, 2008
November 30, 2009
May 2008
April 2009   (final data collection date for primary outcome measure)
  • Pittsburgh Sleep Quality Index [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Epworth Sleepiness Scale [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00594256 on ClinicalTrials.gov Archive Site
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • MATRICS+ neurocognitive battery [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Polysomnographic Measures [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Sodium Oxybate in Schizophrenia With Insomnia
Open Label, Pilot Study of Adjunctive Xyrem (Sodium Oxybate) for the Treatment of Schizophrenia and Associated Sleep Disturbances

The present protocol proposes study of the recently approved compound sodium oxybate (Xyrem), a GABAB and a g-hydroxybutyric acid (GHB) receptor agonist, for the study of persistent symptoms of schizophrenia. Sodium oxybate is a central nervous system depressant currently approved for treatment of narcolepsy associated with cataplexy and excessive daytime sleepiness. In addition to evaluating effects on sodium oxybate on persistent symptoms and neurocognitive deficits in schizophrenia, the study will test the hypothesis that this medication may be particularly effective in combating Insomnia Related to Schizophrenia, and in normalizing symptomatic and polysomnographic manifestations of sleep-related brain dysfunction in schizophrenia.

Rationale/Study Hypothesis:

Rationale for study of sodium oxybate is twofold: first, sleep dysfunction is an important and overlooked aspect of schizophrenia intrinsically linked to cognitive and functional impairments, and, second, GABAB receptors regulate dopaminergic and glutamatergic systems in vivo, suggesting that GABAB agonists may be therapeutically beneficial in schizophrenia.

We are aware of three previous trials of GHB in schizophrenia, two of which did not show any overall benefit in psychopathology. We noted multiple limitations in the controlled trials, including:

  1. requirement of cumbersome dosing patterns (up to six times a day) that could have led to incomplete compliance,
  2. lack of objective measures of subjective sleep or sleep architecture,
  3. lack of objective cognitive testing,
  4. use of GHB as monotherapy or only in conjunction with only low dose antipsychotics,
  5. short trial duration (less than 4 weeks),
  6. relatively low overall night-time dose of GHB, and
  7. a heterogeneous, small sample.

We propose an open label, proof of concept study evaluating the effect of sodium oxybate on insomnia in schizophrenia. The primary hypothesis of the study is that patients treated with sodium oxybate will show improved subjective sleep as measured by the overall Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Secondarily, we expect superior reduction in total psychopathology and PANSS factor scales (PANSS), polysomnographic measures, and neurocognition (MATRICS).

Design and dosage schedule:

We plan to enroll eight hospitalized patients with DSM-IV-TR schizophrenia and insomnia related to schizophrenia. The study will include: a one-week evaluation period, which will include tapering of any hypnotics, baseline diagnostic, psychopathology, neurocognitive, electrophysiological and polysomnographic measurements. Patients will then begin a four-week trial of adjunctive sodium oxybate, with a three-week taper of sodium oxybate to follow. Hypnotic/sodium oxybate taper may be extended or abbreviated, depending on clinical judgment.

Patients entering the study will be permitted to receive both typical and atypical antipsychotics. Treating psychiatrists will be encouraged to maintain fixed doses of all psychotropic medication throughout the study.

Other than haloperidol and benztropine prn (up to 10 mg/day of haloperidol), the prescription of a new psychotropic will not be permitted. After the second week of study medication, any subject requiring more than 4 doses of haloperidol in one week will be considered to have relapsed, and will be withdrawn from the study.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Schizophrenia
  • Insomnia Associated to Schizophrenia
Drug: Sodium Oxybate
Patients will undergo a one-week evaluation period, which will include a taper and discontinuation of any currently prescribed sedative/hypnotics, as well as baseline diagnostic, psychopathology, neurocognitive and polysomnographic measurements (see below for details). Hypnotic taper may be extended or abbreviated, depending on clinical judgment. Patients will then begin a 4-week trial of adjunctive Xyrem (sodium oxybate). Patients will begin at 4.5 g/night (in divided doses of 2.25 g, with 1st dose at bedtime and then 2nd dose four hours later). Dosage will increase by 1.5 g/day every week, until a dose of 9 g nightly is reached, or a patient cannot tolerate further dose escalations. Medication will be administered in divided dosage for the duration of the study. A three-week taper (by 3 g/day weekly) of sodium oxybate will follow the four-week trial of sodium oxybate.
Other Name: Xyrem
Experimental: A
Intervention: Drug: Sodium Oxybate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
8
April 2009
April 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients aged 18-45 with a SCID DSM-IV-TR diagnosis of schizophrenia and insomnia related to schizophrenia, confirmed by SCID.

Exclusion Criteria:

  • Lack of capacity to give informed consent (capacity is determined by a licensed member of the treatment team).
  • Unstable medical illness.
  • Diagnosis of restless leg syndrome, a seizure disorder, uncontrolled hypertension, unstable cardiac illness, or obstructive sleep apnea.
  • Pregnancy or lack of adequate birth control.
  • History of substance dependence disorder.
  • Current treatment with valproic acid.
  • Succinic semialdehyde dehydrogenase deficiency (SSADH).
  • Persistent need for treatment with benzodiazepines, barbiturates, opiates or other sedative hypnotics.
Both
18 Years to 45 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00594256
07I/C36-0
No
Daniel Javitt, MD, PhD, Nathan Kline Institute
Nathan Kline Institute for Psychiatric Research
Jazz Pharmaceuticals
Principal Investigator: Daniel C Javitt, MD PhD Nathan Kline Institute for Psychiatric Research
Nathan Kline Institute for Psychiatric Research
November 2009

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