Glutamate, Learning, and Working Memory

NCT02769936 | Completed Phase 1

• 1 other identifier: 13-000409
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

Impairments in plasticity and working memory in schizophrenia have been hypothesized to reflect dysfunction at the N-methyl-D-aspartate glutamate receptor (NMDAR). However, the specific mechanisms through which the NMDAR is involved in working memory versus plasticity differ. Towards gaining a deeper understanding of how NMDAR signaling relates to individual cognitive functions in healthy adults and patients with schizophrenia, the investigators used a single dose of d-cycloserine (DCS) as an experimental probe to examine the effects of enhancing NMDAR signaling on plasticity versus working memory in healthy adults and individuals with schizophrenia.

Conditions

Schizophrenia

Keywords

Receptors; N-Methyl-D-Aspartate

Outcome Measures

Primary Outcomes (4)

• Performance on Information Integration Learning Task

  Percent Correct Responses out of 240 trials (for schizophrenia patients) or 320 trials (for healthy adults) on the Information Integration Learning Task, which is a classification learning task in which participants learn to classify visual stimuli as category A or B following practice with stimuli and auditory feedback indicating correct versus incorrect responses.

  Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)

• Performance on Weather Prediction Learning Task

  Percent Correct Responses out of 240 trials (for schizophrenia patients) or 320 trials (for healthy adults) on the Weather Prediction Learning Task, which is a probabilistic classification learning task in which participants learn to predict the weather (i.e. "sun" or "rain" outcomes) based on combinations of cues that predict "sun" versus "rain" outcomes.

  Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)

• Performance on N-Back Working Memory Task

  Percent Correct Responses out of 240 trials (for schizophrenia patients) or 320 trials (for healthy adults) on the N-Back Task, which is a spatial working memory task in which participants identify whether each new stimulus on the computer screen is in the same location as the stimulus shown in trials ago. Patients with schizophrenia completed 80 trials at each of 3 working memory loads (0-, 1-, 2-back loads) and healthy adults completed 80 trials at each of 4 working memory loads (0-, 1-, 2-, 3-back loads).

  Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)

• Change in Visual Evoked Potential Amplitude using Electroencephalograph (EEG)

  EEG data were recorded using a 128 channel cap while participants viewed a black and white checkerboard stimulus on a computer screen in 6 x 2-minute blocks before and after viewing a quickly flashing checkerboard stimulus for 2 minutes. Change in the mean amplitude of the visual evoked potential from before versus after viewing the quickly flashing checkerboard stimulus was used to assess plasticity.

  Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)

Study Arms (4)

Healthy Adult - Placebo

PLACEBO COMPARATOR

Single dose placebo pill in healthy adults

Other: Placebo

Healthy Adult - D-cycloserine

EXPERIMENTAL

Single 100 mg dose D-cycloserine pill in healthy adults

Drug: D-cycloserine

Schizophrenia - Placebo

PLACEBO COMPARATOR

Single dose placebo pill in schizophrenia patients

Other: Placebo

Schizophrenia - D-cycloserine

EXPERIMENTAL

Single 100 mg dose D-cycloserine pill in schizophrenia patients

Drug: D-cycloserine

Interventions

D-cycloserine DRUG

100 mg D-cycloserine administered orally as encapsulated pill

Healthy Adult - D-cycloserine; Schizophrenia - D-cycloserine

Placebo OTHER

Placebo administered orally as encapsulated pill

Healthy Adult - Placebo; Schizophrenia - Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• between the ages of 18 and 30 years
• comfortable reading in English
• normal visual acuity or corrected vision
• normal or corrected hearing.

You may not qualify if:

• history or seizures or neurologic diseases
• currently prescribed medication for any psychiatric conditions
• any medical condition affecting fine motor movement of the hands
• pregnancy or suspected pregnancy
• use of recreational drugs or drugs taken not as prescribed in the past month
• having a full scale intelligence quotient (IQ) \< 70, as assessed by the Wechsler Abbreviated Scale of Intelligence (WASI)
• having consumed alcohol in the 24 hours prior to the first lab visit
• known allergy to any antibiotics.
• between the ages of 18 and 50 years
• comfortable reading in English
• normal visual acuity or corrected vision
• normal or corrected hearing
• meets criteria for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) diagnosis of schizophrenia.
• history or seizures or neurologic diseases
• currently prescribed Clozapine or medications contraindicated for DCS

Sponsors & Collaborators

• University of California, Los Angeles: lead

MeSH Terms

Conditions

Schizophrenia

Interventions

Cycloserine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 12, 2016
• Study Start: November 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 12, 2016

Record last verified: 2016-05