A Phase 2 interventional study of Sodium Oxybate in Schizophrenia and Insomnia Related to Schizophrenia (307.42), sponsored by Nathan Kline Institute for Psychiatric Research. Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2016-02-08.
Sponsored by Nathan Kline Institute for Psychiatric Research · Phase 2, Interventional, and Treatment
The present protocol proposes study of the recently approved compound sodium oxybate (Xyrem), a gamma-aminobutyric acid type b (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:
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 diagnostic \& statistical manual text revision (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.
3,539 studies on the registry are indexed under Schizophrenia; 473 are open to participants now.
This study's enrollment of 8 is below the median of 70 across 2,924 interventional studies indexed under Schizophrenia.
Browse Schizophrenia studies →Nathan Kline Institute for Psychiatric Research is the lead sponsor of 23 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
Active treatment
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.
Also known as: Xyrem
Pittsburgh Sleep Quality Index
This rating scale generates a global sleep-quality score, as well as scores on 7 components of sleep quality: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The 19 items are combined to form seven "component" scores, each of which has a range of O-3 points. The seven component scores are then added to yield one "global" score, with a range of O-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all areas.
Time frame: 1 month
Epworth Sleepiness Scale
Designed to measure daytime sleepiness. 8 items rated 0-3, with higher scores associated with a greater daytime sleepiness. overall score rated 0-24, with scores greater than 10 indicating significant daytime sleepiness.
Time frame: 1 month
Positive and Negative Syndrome Scale (PANSS) Negative Factor
The PANSS Negative factor is a 7-item rating scale widely used in the assessment of schizophrenia. Range is 7-49 with higher scores worse
Time frame: 1 month
MATRICS Neurocognitive Battery Composite
This is a series of neurocognitive tests developed by the National Institute of Mental Health to evaluate medications targeting cognition in an efficient and reliable manner. It will be modified by the deletion of the social competence domain. The six domains include speed of processing, attention/vigilance, working memory, verbal learning, visual learning and reasoning/problem solving. The primary outcome will be the mean T-score (mean of six domains).
Time frame: 1 month
Slow Wave Sleep Minutes
Overnight sleep study: Subjects will undergo polysomnography four times during this study, on consecutive nights during the observation week and on consecutive nights at the end. Polysomnography will be performed in a modified seclusion room on the in patient unit. The first of the consecutive nights will be used for adaptation to the study conditions. Sleep was recorded between lights off (10 pm) and lights on (at 6:45 am). We aim for conditions for falling asleep as comfortable as possible under the experimental condition.
Time frame: 1 month
Rockland Psychiatric Center
| Milestone | Sodium Oxybate (Open Label) |
|---|---|
| Started | 8 |
| Completed | 8 |
| Not completed | 0 |
This rating scale generates a global sleep-quality score, as well as scores on 7 components of sleep quality: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The 19 items are combined to form seven "component" scores, each of which has a range of O-3 points. The seven component scores are then added to yield one "global" score, with a range of O-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all areas.
| global score | Sodium Oxybate |
|---|---|
| Pittsburgh Sleep Quality Index | 6.1 ± 3.7 |
Designed to measure daytime sleepiness. 8 items rated 0-3, with higher scores associated with a greater daytime sleepiness. overall score rated 0-24, with scores greater than 10 indicating significant daytime sleepiness.
| global score | Sodium Oxybate |
|---|---|
| Epworth Sleepiness Scale | 4.8 ± 4.6 |
The PANSS Negative factor is a 7-item rating scale widely used in the assessment of schizophrenia. Range is 7-49 with higher scores worse
| mean decrease in negative subscale | Sodiumn Oxybate |
|---|---|
| Positive and Negative Syndrome Scale (PANSS) Negative Factor | 2.8 ± 3.2 |
This is a series of neurocognitive tests developed by the National Institute of Mental Health to evaluate medications targeting cognition in an efficient and reliable manner. It will be modified by the deletion of the social competence domain. The six domains include speed of processing, attention/vigilance, working memory, verbal learning, visual learning and reasoning/problem solving. The primary outcome will be the mean T-score (mean of six domains).
| Composite T-score | Sodium Oxybate |
|---|---|
| MATRICS Neurocognitive Battery Composite | -.26 ± 3.8 |
Overnight sleep study: Subjects will undergo polysomnography four times during this study, on consecutive nights during the observation week and on consecutive nights at the end. Polysomnography will be performed in a modified seclusion room on the in patient unit. The first of the consecutive nights will be used for adaptation to the study conditions. Sleep was recorded between lights off (10 pm) and lights on (at 6:45 am). We aim for conditions for falling asleep as comfortable as possible under the experimental condition.
| minutes | Sodium Oxybate |
|---|---|
| Slow Wave Sleep Minutes | 34.1 ± 26.0 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sodium Oxybate (Open Label) | — | 0/8 (0%) | 5/8 (62.5%) |
| Event | Sodium Oxybate (Open Label) |
|---|---|
| nauseaGastrointestinal disorders | 2/8 |
| nocturnal enuresisRenal and urinary disorders | 2/8 |
| agitationPsychiatric disorders | 1/8 |
| Age, Categorical(Participants) | Sodium Oxybate (Open Label) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 8 |
| >=65 years | 0 |
| Age, Continuous(years) | Sodium Oxybate (Open Label) |
|---|---|
| Mean | 41.8 ± 10 |
| Sex: Female, Male(Participants) | Sodium Oxybate (Open Label) |
|---|---|
| Female | 1 |
| Male | 7 |
| Region of Enrollment(participants) | Sodium Oxybate (Open Label) |
|---|---|
| United States | 8 |
This study is completed, as verified in Jan 2016. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sodium Oxybate
Nathan Kline Institute for Psychiatric Research