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D-serine AudRem: R33 Phase

Primary Purpose

Schizophrenia, Schizo Affective Disorder

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

D-serine

Placebo

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
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

Exclusion Criteria:

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

Sites / Locations

NYSPIRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

D-serine

placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

Auditory Cognition

MATRICS cognitive battery verbal domain

Secondary Outcome Measures

Full Information

NCT ID

NCT05046353

First Posted

August 30, 2021

Last Updated

January 3, 2023

Sponsor

New York State Psychiatric Institute

Collaborators

Nathan Kline Institute for Psychiatric Research, National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT05046353

Brief Title

D-serine AudRem: R33 Phase

Official Title

D-serine Augmentation of Neuroplasticity-based Auditory Learning in Schizophrenia: R33 Phase

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2022 (Actual)

Primary Completion Date

April 1, 2024 (Anticipated)

Study Completion Date

August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

New York State Psychiatric Institute

Collaborators

Nathan Kline Institute for Psychiatric Research, National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Schizo Affective Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

D-serine

Arm Type

Experimental

Arm Description

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.

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

D-serine

Intervention Description

Auditory remediation +/-D-serine

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Auditory remediation +/-D-serine

Primary Outcome Measure Information:

Title

Auditory Cognition

Description

MATRICS cognitive battery verbal domain

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Joshua Kantrowitz

Phone

6467748496

joshua.kantrowitz@nyspi.columbia.edu

Facility Information:

Facility Name

NYSPI

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joshua Kantrowitz

Phone

646-774-8496

Joshua.kantrowitz@nyspi.columbia.edu

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Will likely be available at https://nda.nih.gov

Learn more about this trial

D-serine AudRem: R33 Phase

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