Glutamate, Learning, and Working Memory
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
D-cycloserine
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Schizophrenia focused on measuring Receptors, N-Methyl-D-Aspartate
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
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
NCT ID
NCT02769936
First Posted
May 10, 2016
Last Updated
May 11, 2016
Sponsor
University of California, Los Angeles
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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