SchizophreniaPhase 1/2NCT05046353
D-serine AudRem: R33 Phase
A Phase 1/2 study testing D-serine in people with Schizophrenia and Schizo Affective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Schizophrenia is a major public health problem associated with cognitive deficits, such as short and long term memory, executive functioning, attention and speed of processing that are amongst the strongest predictors of impaired functional outcome. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Schizophrenia, Schizo Affective Disorder
- What is being tested?
- D-serine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2022to 1 Sep 2027
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 18 and 50
- DSM-V diagnosis of schizophrenia or schizoaffective disorder
- Willing to provide informed consent
- Auditory Cognitive impairment demonstrated by:
- a .MCCB composite domain score less than or equal to 0.5 standard deviation below normal (T score less than or equal to 45) b. And at least one of the following:
- MCCB verbal memory domain score less than or equal to 0.5 standard deviation below normal (T score less than or equal to 45)
Show all 17Show fewer
- Tone matching score of less than or equal to 77.7%
- Clinically stable for 2 months (CGI less than or equal to 4)
- Moderate or lower cognitive disorganization (PANSS P2 less than or equal to 4)
- Medically stable for study participation
- Willing to use qualified methods of contraception for the study duration and up to 2 months after its end
- Fluent English speaker
- Normal hearing
- Visual acuity corrected to 20/30
- An estimated Glomerular Filtration Rate (GFR) greater than or equal to 60
- Taking an antipsychotic medication other than clozapine at a stable dose for at least 4 weeks
- Judged clinically not to be at significant suicide or violence risk
Who cannot join
- Substance abuse (excluding nicotine) within last 60 days
- ECG abnormality that is clinically significant in the context of study participation in the opinion of the study cardiologist
- Current clozapine use. Clozapine is excluded for two reasons: to avoid the potential confound of treatment resistant patients and because of clozapine's intrinsic NMDA agonist
- Participation in study of investigational medication/device within 4 weeks
- Pregnant women or women of child-bearing potential, who are either not surgically-sterile or for outpatients, using appropriate methods of birth control. Women of child-bearing potential must have a negative serum beta-hCG pregnancy test at screening.
- Presence of positive history of unstable significant medical or neurological illness
- Positive toxicology screen for any substances of abuse
- Subjects with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: D-serine Augmentation of Neuroplasticity-based Auditory Learning in Schizophrenia: R33 Phase
Schizophrenia is a major public health problem associated with cognitive deficits, such as short and long term memory, executive functioning, attention and speed of processing that are amongst the strongest predictors of impaired functional outcome. In addition, schizophrenia patients show reduced "plasticity", defined as reduced learning.
D-serine is a naturally occurring activator of the N-methyl-d-aspartate-type glutamate receptors (NMDAR) in the brain, and this project will assess the D-serine treatment over 16 weeks of a program designed to measure auditory plasticity.
Read the detailed description
D-Serine is a naturally occurring substance in the brain that activates the N-methyl-d-aspartate-type glutamate receptor (NMDAR). This receptor is thought to be important in both schizophrenia and plasticity (learning). My model proposes that problems with NMDAR within the brain leads to impaired plasticity, which in turn leads to impaired cognition. d-serine is an ideal NMDAR activator to study because it balances efficacy, availability and safety. Most d-serine studies have used a low dose, but the evidence for efficacy is even stronger for high dose d-serine, as will be tested in the current study. There has only been limited summary of higher dose d-serine, which is another important reason for this study.
In addition to testing a potentially viable treatment in schizophrenia, a positive result would provide opportunities for use of D-serine in other populations (e.g. anxiety disorders or dementia) and stimulate the pharmaceutical industry to utilize this methodology to assess the efficacy of novel NMDAR modulators, using d-serine as a "gold-standard."
The ultimate goal of this two part grant (R61-R33) study is to improve cognitive remediation by augmenting with D-serine.
We recently completed the R61-phase, meeting our predetermined "milestones. " As predicted, D-serine led to significant enhancement of auditory plasticity and electrophysiological measures.
During the three-year R33-phase, we will conduct a study of D-serine of 60 schizophrenia patients, assessing the effects of D-serine over 16 sessions of this program. Most successful, cognitive remediation programs are limited by lengthy (30-50 hours) treatments. Hypothesizing that adding D-serine will increase efficiency of cognitive remediation, successful completion of the R33-phase is defined as significant improvement in global cognition after 16 hours of treatment, and will serve as a pilot study to determine whether future, definitive clinical trials are warranted.
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Being tested
- D-serine, Placebo
- 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
Auditory remediation +/-D-serine
PlaceboOther
Auditory remediation +/-D-serine
| Study group | Role | What they receive |
|---|---|---|
| D-serine | Experimental | Subjects will receive 16 sessions of auditory remediation paired with either D-serine or Placebo in a 1:1 D-serine 120 mg/kg:placebo ratio. Receives: Drug: D-serine |
| placebo | Placebo comparator | Subjects will receive 16 sessions of auditory remediation paired with either D-serine or Placebo in a 1:1 D-serine 120 mg/kg:placebo ratio. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Auditory Cognition
MATRICS cognitive battery verbal domain
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2021
- Study start1 Dec 2022
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Sep 2027 (estimated)
Why it stopped: U.S. Department of Health and Human Services OHRP issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023. NKI site is open for enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Nathan Kline Institute for Psychiatric Research, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Joshua Kantrowitz, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05046353
- Sponsor's protocol ID
- 7725R
- Status last verified
- Apr 2026
- First submitted
- 30 Aug 2021
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Will likely be available at https://nda.nih.gov
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- D-serine Augmentation of Neuroplasticity-based Auditory Learning in Schizophrenia: R33 Phase
- ClinicalTrials.gov ID
- NCT05046353
- Acronym / sponsor ID
- 7725R
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: U.S. Department of Health and Human Services OHRP issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023. NKI site is open for enrollment.
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Nathan Kline Institute for Psychiatric Research, National Institute of Mental Health (NIMH)
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 16 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Schizophrenia is a major public health problem associated with cognitive deficits, such as short and long term memory, executive functioning, attention and speed of processing that are amongst the strongest predictors of impaired functional outcome. In addition, schizophrenia patients show reduced "plasticity", defined as reduced learning.
D-serine is a naturally occurring activator of the N-methyl-d-aspartate-type glutamate receptors (NMDAR) in the brain, and this project will assess the D-serine treatment over 16 weeks of a program designed to measure auditory plasticity.
Detailed description
D-Serine is a naturally occurring substance in the brain that activates the N-methyl-d-aspartate-type glutamate receptor (NMDAR). This receptor is thought to be important in both schizophrenia and plasticity (learning). My model proposes that problems with NMDAR within the brain leads to impaired plasticity, which in turn leads to impaired cognition. d-serine is an ideal NMDAR activator to study because it balances efficacy, availability and safety. Most d-serine studies have used a low dose, but the evidence for efficacy is even stronger for high dose d-serine, as will be tested in the current study. There has only been limited summary of higher dose d-serine, which is another important reason for this study.
In addition to testing a potentially viable treatment in schizophrenia, a positive result would provide opportunities for use of D-serine in other populations (e.g. anxiety disorders or dementia) and stimulate the pharmaceutical industry to utilize this methodology to assess the efficacy of novel NMDAR modulators, using d-serine as a "gold-standard."
The ultimate goal of this two part grant (R61-R33) study is to improve cognitive remediation by augmenting with D-serine.
We recently completed the R61-phase, meeting our predetermined "milestones. " As predicted, D-serine led to significant enhancement of auditory plasticity and electrophysiological measures.
During the three-year R33-phase, we will conduct a study of D-serine of 60 schizophrenia patients, assessing the effects of D-serine over 16 sessions of this program. Most successful, cognitive remediation programs are limited by lengthy (30-50 hours) treatments. Hypothesizing that adding D-serine will increase efficiency of cognitive remediation, successful completion of the R33-phase is defined as significant improvement in global cognition after 16 hours of treatment, and will serve as a pilot study to determine whether future, definitive clinical trials are warranted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-serine | Experimental | Drug: D-serineSubjects will receive 16 sessions of auditory remediation paired with either D-serine or Placebo in a 1:1 D-serine 120 mg/kg:placebo ratio. |
| placebo | Placebo comparator | Other: PlaceboSubjects will receive 16 sessions of auditory remediation paired with either D-serine or Placebo in a 1:1 D-serine 120 mg/kg:placebo ratio. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Age between 18 and 50
- DSM-V diagnosis of schizophrenia or schizoaffective disorder
- Willing to provide informed consent
- Auditory Cognitive impairment demonstrated by:
- a .MCCB composite domain score less than or equal to 0.5 standard deviation below normal (T score less than or equal to 45) b. And at least one of the following:
Key exclusion criteria (8 listed)
- Substance abuse (excluding nicotine) within last 60 days
- ECG abnormality that is clinically significant in the context of study participation in the opinion of the study cardiologist
- Current clozapine use. Clozapine is excluded for two reasons: to avoid the potential confound of treatment resistant patients and because of clozapine's intrinsic NMDA agonist
- Participation in study of investigational medication/device within 4 weeks
- Pregnant women or women of child-bearing potential, who are either not surgically-sterile or for outpatients, using appropriate methods of birth control. Women of child-bearing potential must have a negative serum beta-hCG pregnancy test at screening.
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-serineAuditory remediation +/-D-serine | Drug | D-serine |
| PlaceboAuditory remediation +/-D-serine | Other | placebo |
Primary outcome
Auditory Cognition
Time frame: 16 weeks
MATRICS cognitive battery verbal domain
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: Undecided. Will likely be available at https://nda.nih.gov
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing D-serine in people with Schizophrenia and Schizo Affective Disorder, run by New York State Psychiatric Institute 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 17 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: paused, as of the sponsor's last update on 29 Apr 2026. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
Auditory Cognition (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Apr 2026.