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
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Insomnia Associated to Schizophrenia
Drug: Sodium Oxybate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Pilot Study of Adjunctive Xyrem (Sodium Oxybate) for the Treatment of Schizophrenia and Associated Sleep Disturbances

Resource links provided by NLM:


Further study details as provided by Nathan Kline Institute for Psychiatric Research:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 8
Study Start Date: May 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00594256

Locations
United States, New York
Nathan Kline Insitute for Psychiatric Research
Orangeburg, New York, United States, 10962
Sponsors and Collaborators
Nathan Kline Institute for Psychiatric Research
Jazz Pharmaceuticals
Investigators
Principal Investigator: Daniel C Javitt, MD PhD Nathan Kline Institute for Psychiatric Research
  More Information

No publications provided

Responsible Party: Daniel Javitt, MD, PhD, Nathan Kline Institute
ClinicalTrials.gov Identifier: NCT00594256     History of Changes
Other Study ID Numbers: 07I/C36-0
Study First Received: January 3, 2008
Last Updated: November 30, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Nathan Kline Institute for Psychiatric Research:
Schizophrenia
Sleep Architecture
Sodium Oxybate
Insomnia
Cognition

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Sodium Oxybate
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014