SchizophreniaPhase 2NCT00817336
Biomarkers in Schizophrenia
A Phase 2 study testing D Serine in people with Schizophrenia and Schizoaffective Disorder, run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.
Trial summary
N-methyl-D-aspartate (NMDA)-type glutamate receptors are thought to play a pivotal role in neurocognitive dysfunction associated with schizophrenia. Further, several novel glutamate-based classes of compound are presently in development as potential novel treatments for persistent negative and cognitive symptoms. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- D Serine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2009to Jul 2011
- 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-64
- SCID diagnosis of Schizophrenia or Schizoaffective Disorder.
- PANSS 3 factor negative symptom (screening and baseline visit 1 and visit 3) score of >20 and PANSS total score between 60-110. Any degree of positive symptoms is acceptable but the total PANSS score must not exceed 110.
- SAS total score less than or equal to 12 and a Calgary Depression Inventory total score less than or equal to 10 and suicide (item 8) less than moderate (<2).
- Two consecutive CGI ratings at screening and baseline (visit 1 and 3) with no change in score.
- Estimated Glomerular Filtration Rate (GFR)(a measure of renal function) greater than or equal to 60.
Who cannot join
- Organic brain disorder, including epilepsy; mental retardation; or a medical condition whose pathology or treatment would likely alter the presentation or treatment of schizophrenia or significantly increase the risk associated with any of the proposed treatments
- Current DSM-IV diagnosis of drug/alcohol abuse in last month and current DSM-IV diagnosis of drug/alcohol dependence in last 6 months
- Pregnant female patients
- Impaired renal function
- Significant extrapyramidal symptoms (as reflected by a total score of 10 or above on the SAS scale), and depressive symptoms (as reflected by a score of 10 or above on the Calgary Depression Scale for Schizophrenia)
- Patients who are unable to or unwilling to participate in the Cognitive assessment (MATRICS) and the electrophysiology tasks .
- Patients on clozapine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia
N-methyl-D-aspartate (NMDA)-type glutamate receptors are thought to play a pivotal role in neurocognitive dysfunction associated with schizophrenia. Further, several novel glutamate-based classes of compound are presently in development as potential novel treatments for persistent negative and cognitive symptoms. The study will assess effectiveness of a NMDA-based intervention on biomarkers related to schizophrenia as a mechanism for developing appropriate outcome batteries for future trials of novel compounds.
Read the detailed description
16 in- or outpatients with DSM-IV-TR schizophrenia or schizoaffective disorder and prominent negative symptoms will be recruited for this study. This study will consist of a randomized trial of D-serine (60 mg/kg/d) vs. placebo using a crossover design with a 2-week baseline lead-in, and two 6-week intervention arms separated by a two week, placebo controlled washout period. Biomarkers will be assessed at baseline for each treatment arm, acutely (day 7) following treatment initiation, and following 6 weeks of treatment (6 biomarker sessions total). Primary biomarker outcome measures will include 1) amplitude of the mismatch negativity (MMN) waveform and 2) amplitude of the visual P1 potential. Symptomatic outcome measures will include PANSS and composite score of the MATRICS neuropsychological battery. The study will be supported from ongoing NIMH-funded Cooperative Drug Development Grant (CDDG) to the PI.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- D Serine, Placebo
- Keywords
- biomarker, EEG, schizophrenia, NMDA, D-serine
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D SerineDrug
60 mg/kg/day
PlaceboDrug
oral
| Study group | Role | What they receive |
|---|---|---|
| D-serine | Experimental | 60 mg/kg/day Receives: Drug: D Serine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PANSS Total
Positive and Negative Symptom Scale (PANSS) range 30-210
Measured: 6 weeks
MMN Amplitude
Final MMN amplitude
Measured: 6 weeks
Secondary outcomes (2)
MATRICS
MATRICS assessing 7 domains (Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. Raw scores are converted into a composite T-score (normative mean = 50; standard deviation = 10), where higher values indicated less impairment.
Measured: 6 weeks
Visual P1
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2009 (estimated)
- Study startJun 2009
- Primary completionJul 2011
- Study completionJul 2011
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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Kline Institute for Psychiatric Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel C Javitt, MD, PhD, Principal investigator, New York University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817336
- Sponsor's protocol ID
- 08I/C19-0
- Status last verified
- Jul 2017
- First submitted
- 5 Jan 2009
- Last updated
- 2 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, Petkova E, Silipo G, Javitt DC. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018 Jan;191:70-79. doi: 10.1016/j.schres.2017.02.027. Epub 2017 Mar 18.
PubMed 28318835
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia
- ClinicalTrials.gov ID
- NCT00817336
- Acronym / sponsor ID
- 08I/C19-0
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- biomarker, EEG, schizophrenia, NMDA, D-serine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 6 Jan 2009 (estimated)
- Results
- Posted 2 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
N-methyl-D-aspartate (NMDA)-type glutamate receptors are thought to play a pivotal role in neurocognitive dysfunction associated with schizophrenia. Further, several novel glutamate-based classes of compound are presently in development as potential novel treatments for persistent negative and cognitive symptoms. The study will assess effectiveness of a NMDA-based intervention on biomarkers related to schizophrenia as a mechanism for developing appropriate outcome batteries for future trials of novel compounds.
Detailed description
16 in- or outpatients with DSM-IV-TR schizophrenia or schizoaffective disorder and prominent negative symptoms will be recruited for this study. This study will consist of a randomized trial of D-serine (60 mg/kg/d) vs. placebo using a crossover design with a 2-week baseline lead-in, and two 6-week intervention arms separated by a two week, placebo controlled washout period. Biomarkers will be assessed at baseline for each treatment arm, acutely (day 7) following treatment initiation, and following 6 weeks of treatment (6 biomarker sessions total). Primary biomarker outcome measures will include 1) amplitude of the mismatch negativity (MMN) waveform and 2) amplitude of the visual P1 potential. Symptomatic outcome measures will include PANSS and composite score of the MATRICS neuropsychological battery. The study will be supported from ongoing NIMH-funded Cooperative Drug Development Grant (CDDG) to the PI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-serine | Experimental | Drug: D Serine60 mg/kg/day |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Age 18-64
- SCID diagnosis of Schizophrenia or Schizoaffective Disorder.
- PANSS 3 factor negative symptom (screening and baseline visit 1 and visit 3) score of >20 and PANSS total score between 60-110. Any degree of positive symptoms is acceptable but the total PANSS score must not exceed 110.
- SAS total score less than or equal to 12 and a Calgary Depression Inventory total score less than or equal to 10 and suicide (item 8) less than moderate (<2).
- Two consecutive CGI ratings at screening and baseline (visit 1 and 3) with no change in score.
Key exclusion criteria (7 listed)
- Organic brain disorder, including epilepsy; mental retardation; or a medical condition whose pathology or treatment would likely alter the presentation or treatment of schizophrenia or significantly increase the risk associated with any of the proposed treatments
- Current DSM-IV diagnosis of drug/alcohol abuse in last month and current DSM-IV diagnosis of drug/alcohol dependence in last 6 months
- Pregnant female patients
- Impaired renal function
- Significant extrapyramidal symptoms (as reflected by a total score of 10 or above on the SAS scale), and depressive symptoms (as reflected by a score of 10 or above on the Calgary Depression Scale for Schizophrenia)
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 |
|---|---|---|
| D Serine60 mg/kg/day | Drug | D-serine |
| Placebooral | Drug | Placebo |
Primary outcome
PANSS Total
Time frame: 6 weeks
Positive and Negative Symptom Scale (PANSS) range 30-210
MMN Amplitude
Time frame: 6 weeks
Final MMN amplitude
2 secondary outcomes
MATRICS
Time frame: 6 weeks
Visual P1
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28318835Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, Petkova E, Silipo G, Javitt DC. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018 Jan;191:70-79. doi: 10.1016/j.schres.2017.02.027. Epub 2017 Mar 18.
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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
New York University
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 D Serine in people with Schizophrenia and Schizoaffective Disorder, 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 6 inclusion and 7 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 2 Aug 2017. 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. Some participants in this study may receive a placebo. 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 2 Aug 2017). 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?
PANSS Total (time frame: 6 weeks). 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 NCT00817336, 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 2 Aug 2017; AzTrials last refreshed its copy on 29 Oct 2026.