SchizophreniaPhase 2NCT00594256
Sodium Oxybate in Schizophrenia With Insomnia
A Phase 2 study testing Sodium Oxybate in people with Schizophrenia and Insomnia Related to Schizophrenia (307.42), run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Schizophrenia, Insomnia Related to Schizophrenia (307.42)
- What is being tested?
- Sodium Oxybate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Apr 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients aged 18-45 with a DSM-IV diagnosis of schizophrenia and insomnia related to schizophrenia, confirmed by a structured interview (SCID).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Nathan Kline Insitute for Psychiatric Research
Orangeburg, New York, 10962
About this study
Official title: 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 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.
Read the 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:
- requirement of cumbersome dosing patterns (up to six times a day) that could have led to incomplete compliance,
- lack of objective measures of subjective sleep or sleep architecture,
- lack of objective cognitive testing,
- use of GHB as monotherapy or only in conjunction with only low dose antipsychotics,
- short trial duration (less than 4 weeks),
- relatively low overall night-time dose of GHB, and
- 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 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.
- Being tested
- Sodium Oxybate
- Keywords
- Schizophrenia, Sleep Architecture, Sodium Oxybate, Insomnia, Cognition
- Medical subject headings
- Schizophrenia, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium OxybateDrug
Also called Xyrem
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.
| Study group | Role | What they receive |
|---|---|---|
| Sodium oxybate | Experimental | Active treatment Receives: Drug: Sodium Oxybate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 1 month
Secondary outcomes (3)
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
Measured: 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).
Measured: 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.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2008 (estimated)
- Study startMay 2008
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Kline Institute for Psychiatric Research
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Principal investigator, Daniel C. Javitt, MD, PhD, Nathan Kline Institute for Psychiatric Research
- Investigators
- Daniel C Javitt, MD PhD, Principal investigator, Nathan Kline Institute for Psychiatric Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00594256
- Sponsor's protocol ID
- 07I/C36-0
- Status last verified
- Jan 2016
- First submitted
- 3 Jan 2008
- Last updated
- 8 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kantrowitz JT, Oakman E, Bickel S, Citrome L, Spielman A, Silipo G, Battaglia J, Javitt DC. The importance of a good night's sleep: an open-label trial of the sodium salt of gamma-hydroxybutyric acid in insomnia associated with schizophrenia. Schizophr Res. 2010 Jul;120(1-3):225-6. doi: 10.1016/j.schres.2010.03.035. No abstract available.
PubMed 20435443
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label, Pilot Study of Adjunctive Xyrem (Sodium Oxybate) for the Treatment of Schizophrenia and Associated Sleep Disturbances
- ClinicalTrials.gov ID
- NCT00594256
- Acronym / sponsor ID
- 07I/C36-0
- Keywords
- Schizophrenia, Sleep Architecture, Sodium Oxybate, Insomnia, Cognition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- May 2008
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 15 Jan 2008 (estimated)
- Results
- Posted 8 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- requirement of cumbersome dosing patterns (up to six times a day) that could have led to incomplete compliance,
- lack of objective measures of subjective sleep or sleep architecture,
- lack of objective cognitive testing,
- use of GHB as monotherapy or only in conjunction with only low dose antipsychotics,
- short trial duration (less than 4 weeks),
- relatively low overall night-time dose of GHB, and
- 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sodium oxybate | Experimental | Drug: Sodium OxybateActive treatment |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Patients aged 18-45 with a DSM-IV diagnosis of schizophrenia and insomnia related to schizophrenia, confirmed by a structured interview (SCID).
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium OxybateAlso: XyremPatients 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. | Drug | Sodium oxybate |
Primary outcome
Pittsburgh Sleep Quality Index
Time frame: 1 month
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.
Epworth Sleepiness Scale
Time frame: 1 month
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.
3 secondary outcomes
Positive and Negative Syndrome Scale (PANSS) Negative Factor
Time frame: 1 month
MATRICS Neurocognitive Battery Composite
Time frame: 1 month
Slow Wave Sleep Minutes
Time frame: 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20435443Kantrowitz JT, Oakman E, Bickel S, Citrome L, Spielman A, Silipo G, Battaglia J, Javitt DC. The importance of a good night's sleep: an open-label trial of the sodium salt of gamma-hydroxybutyric acid in insomnia associated with schizophrenia. Schizophr Res. 2010 Jul;120(1-3):225-6. doi: 10.1016/j.schres.2010.03.035. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel C Javitt, MD PhD principal investigator
Nathan Kline Institute for Psychiatric Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Oxybate in people with Schizophrenia and Insomnia Related to Schizophrenia (307.42), run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pittsburgh Sleep Quality Index (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00594256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2016.