D-serine AudRem: R33 Phase

NCT05046353 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: 7725R
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Schizo Affective Disorder

Outcome Measures

Primary Outcomes (1)

• Auditory Cognition

  MATRICS cognitive battery verbal domain

  16 weeks

Study Arms (2)

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.

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.

Other: Placebo

Interventions

D-serine DRUG

Auditory remediation +/-D-serine

D-serine

Placebo OTHER

Auditory remediation +/-D-serine

placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• Nathan Kline Institute for Psychiatric Research: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

NYSPI

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 16, 2021
• Study Start: December 1, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (1)