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Glutamate, Learning, and Working Memory

Primary Purpose

Schizophrenia

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
D-cycloserine
Placebo
Sponsored by
University of California, Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Schizophrenia focused on measuring Receptors, N-Methyl-D-Aspartate

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria for healthy subjects:

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

Exclusion criteria for healthy subjects:

  1. history or seizures or neurologic diseases
  2. currently prescribed medication for any psychiatric conditions
  3. any medical condition affecting fine motor movement of the hands
  4. pregnancy or suspected pregnancy
  5. use of recreational drugs or drugs taken not as prescribed in the past month
  6. having a full scale intelligence quotient (IQ) < 70, as assessed by the Wechsler Abbreviated Scale of Intelligence (WASI)
  7. having consumed alcohol in the 24 hours prior to the first lab visit
  8. known allergy to any antibiotics.

Inclusion criteria for patients with schizophrenia:

  1. between the ages of 18 and 50 years
  2. comfortable reading in English
  3. normal visual acuity or corrected vision
  4. normal or corrected hearing
  5. meets criteria for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) diagnosis of schizophrenia.

Exclusion criteria for patients with schizophrenia:

  1. history or seizures or neurologic diseases
  2. currently prescribed Clozapine or medications contraindicated for DCS
  3. any medical condition affecting fine motor movement of the hands
  4. pregnancy or suspected pregnancy
  5. history of traumatic brain injury requiring hospitalization for 2 or more days
  6. IQ < 70, as assessed by the WASI
  7. having consumed drugs other than as prescribed in the 48 hour prior to the testing visit or having consumed alcohol in the 24 hours prior to the testing visit
  8. known allergy to any antibiotics
  9. current alcohol or substance dependence

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Placebo Comparator

    Experimental

    Placebo Comparator

    Experimental

    Arm Label

    Healthy Adult - Placebo

    Healthy Adult - D-cycloserine

    Schizophrenia - Placebo

    Schizophrenia - D-cycloserine

    Arm Description

    Single dose placebo pill in healthy adults

    Single 100 mg dose D-cycloserine pill in healthy adults

    Single dose placebo pill in schizophrenia patients

    Single 100 mg dose D-cycloserine pill in schizophrenia patients

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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).
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    May 10, 2016
    Last Updated
    May 11, 2016
    Sponsor
    University of California, Los Angeles
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02769936
    Brief Title
    Glutamate, Learning, and Working Memory
    Official Title
    The Effects of D-cycloserine on Neuroplasticity and Working Memory in Healthy Adults and Patients With Schizophrenia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2016
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2013 (undefined)
    Primary Completion Date
    July 2015 (Actual)
    Study Completion Date
    December 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of California, Los Angeles

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.
    Detailed Description
    Background: Cognitive impairments in schizophrenia, such as deficits in plasticity and working memory, have been hypothesized to reflect dysfunction at the N-methyl-D-aspartate glutamate receptor (NMDAR). However, given that divergent properties of the NMDAR underlie its roles in plasticity versus working memory and that various aspects of NMDAR function are abnormal in schizophrenia, examining the effects of DCS in both healthy and patient populations is crucial. Methods: The investigators used a single dose of the partial NMDAR agonist, d-cycloserine (DCS) to probe the effects of enhancing NMDAR signaling on working memory and plasticity. Working memory was assessed using a spatial n-back task. Plasticity was assessed using two learning tasks, the weather prediction task and information integration task, and an EEG paradigm that assesses changes in visual evoked potential amplitude following high frequency visual stimulation. Sixty-five healthy adults and forty-five schizophrenia patients were randomized to receive 100 mg acute DCS (healthy adult n = 32; schizophrenia n = 24) or placebo (healthy adult n = 33; schizophrenia n = 21).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Schizophrenia
    Keywords
    Receptors, N-Methyl-D-Aspartate

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    110 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Healthy Adult - Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Single dose placebo pill in healthy adults
    Arm Title
    Healthy Adult - D-cycloserine
    Arm Type
    Experimental
    Arm Description
    Single 100 mg dose D-cycloserine pill in healthy adults
    Arm Title
    Schizophrenia - Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Single dose placebo pill in schizophrenia patients
    Arm Title
    Schizophrenia - D-cycloserine
    Arm Type
    Experimental
    Arm Description
    Single 100 mg dose D-cycloserine pill in schizophrenia patients
    Intervention Type
    Drug
    Intervention Name(s)
    D-cycloserine
    Intervention Description
    100 mg D-cycloserine administered orally as encapsulated pill
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo administered orally as encapsulated pill
    Primary Outcome Measure Information:
    Title
    Performance on Information Integration Learning Task
    Description
    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.
    Time Frame
    Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
    Title
    Performance on Weather Prediction Learning Task
    Description
    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.
    Time Frame
    Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
    Title
    Performance on N-Back Working Memory Task
    Description
    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).
    Time Frame
    Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
    Title
    Change in Visual Evoked Potential Amplitude using Electroencephalograph (EEG)
    Description
    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.
    Time Frame
    Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion criteria for healthy subjects: between the ages of 18 and 30 years comfortable reading in English normal visual acuity or corrected vision normal or corrected hearing. Exclusion criteria for healthy subjects: 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. Inclusion criteria for patients with schizophrenia: 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. Exclusion criteria for patients with schizophrenia: history or seizures or neurologic diseases currently prescribed Clozapine or medications contraindicated for DCS any medical condition affecting fine motor movement of the hands pregnancy or suspected pregnancy history of traumatic brain injury requiring hospitalization for 2 or more days IQ < 70, as assessed by the WASI having consumed drugs other than as prescribed in the 48 hour prior to the testing visit or having consumed alcohol in the 24 hours prior to the testing visit known allergy to any antibiotics current alcohol or substance dependence

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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    Glutamate, Learning, and Working Memory

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