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Orangeburg, New York 10962


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.

Study summary:

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.


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.

Study is Available At:

Original ID:




Secondary ID:

Study Acronym:

Brief Title:

Sodium Oxybate in Schizophrenia With Insomnia

Official Title:

Open Label, Pilot Study of Adjunctive Xyrem (Sodium Oxybate) for the Treatment of Schizophrenia and Associated Sleep Disturbances

Overall Status:


Study Phase:

Phase 2



Minimum Age:

18 Years

Maximum Age:

45 Years

Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Nathan Kline Institute for Psychiatric Research

Oversight Authority:

United States: Institutional Review Board

Reasons Why Stopped:

Study Type:


Study Design:

Endpoint Classification: Efficacy Study, Interven

Number of Arms:


Number of Groups:


Total Enrollment:


Enrollment Type:


Overall Contact Information

Official Name:Daniel C Javitt, MD PhD
Principal Investigator
Nathan Kline Institute for Psychiatric Research

Study Dates

Start Date:May 2008
Completion Date:April 2009
Completion Type:Actual
Primary Completion Date:April 2009
Primary Completion Type:Actual
Verification Date:November 2009
Last Changed Date:November 30, 2009
First Received Date:January 3, 2008

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Polysomnographic Measures
Time Frame:1 month
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:MATRICS+ neurocognitive battery
Time Frame:1 month
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Positive and Negative Syndrome Scale (PANSS)
Time Frame:1 month
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Epworth Sleepiness Scale
Time Frame:1 month
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Pittsburgh Sleep Quality Index
Time Frame:1 month
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Sodium Oxybate
Description: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 1s
Arm Name:A
Other Name:Xyrem

Study Arms

Study Arm Type:Experimental
Arm Name:A

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Nathan Kline Institute for Psychiatric Research
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Jazz Pharmaceuticals

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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