D-serine and Cognitive Remediation in Schizophrenia

D-serine and Cognitive Remediation in Schizophrenia: Open Label Pilot

The investigators will test the effects of 3 days of D-serine (DSR) on auditory plasticity in a sensory based remediation (SBR) paradigm

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: D-serine

Detailed Description

We will enroll 8 subjects in an open label, three session pilot in patients will receive three sessions of tone matching SBR.

5 Subjects will receive D-serine (60mg/kg) taken 1x each week during the SBR sessions. Subjects will receive study drug 30 minutes prior to session.

3 subjects received no intervention

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Orangeburg, New York, United States, 10962
      • Nathan Kline Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• 18 to 64 years old,
• IQ≥85 and
• estimated Glomerular Filtration Rate (GFR) ≥60. All oral and depot antipsychotics (with the exception of clozapine) are allowable. Patients must be on their antipsychotic medication for 1 month and stable on dose of antipsychotic and adjunctive medications for 2 weeks prior to study entry.

Exclusion criteria:

• history of neurological visual or hearing impairment,
• active suicidal ideation on the Columbia Suicide Severity Rating Scale (C-SSRS),
• current alcohol or drug abuse (<1 month) or substance dependence (<4 months). All women of child-bearing potential must have a negative urine pregnancy test at the baseline visit. We require an IQ of ≥85 to ensure that subjects will have a capacity to learn. In our cross-sectional studies, we have observed an IQ≥85 in over 90% of candidates, suggesting that this is not an overly restrictive criterion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D-serine	Drug: D-serine; D-serine 60 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mismatch Negativity (MMN)	An MMN event is evoked by a discernible change in the pitch of a repetitive auditory stimulation. The stronger the response to a difference (i.e., the more negative the amplitude of the MMN), the better the outcome. MMN was obtained to pitch deviant stimuli pre-post auditory plasticity training, utilizing deviants to the same base frequencies as the auditory plasticity sessions, (i.e. 500, 1000, and 2000 Hz), with ~10 minutes of each base frequency. MMN will be conducted at baseline and after the final session. Reported outcome is change in MMN between baseline and final within session.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tone Matching Threshold	Change tone matching threshold (the percent difference in pitch of two consecutively played tones that can be distinguished), higher numbers represent better outcomes. D-serine outcomes are for 2 consecutive D-serine sessions	three weeks

Collaborators and Investigators

• Sponsor: Nathan Kline Institute for Psychiatric Research
• Investigators: Principal Investigator: Joshua T Kantrowitz, MD, Nathan Kline Institute

Publications and helpful links

General Publications

• Kantrowitz JT, Epstein ML, Beggel O, Rohrig S, Lehrfeld JM, Revheim N, Lehrfeld NP, Reep J, Parker E, Silipo G, Ahissar M, Javitt DC. Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine. Brain. 2016 Dec;139(Pt 12):3281-3295. doi: 10.1093/brain/aww262.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 3, 2014
• First Submitted That Met QC Criteria: June 4, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: cognitive remediation
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 601945

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes