SchizophreniaPhase 1NCT02769936
Glutamate, Learning, and Working Memory
A Phase 1 study testing D-cycloserine in people with Schizophrenia, run by University of California, Los Angeles.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- D-cycloserine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- No sites listed yet
- Study dates
- Nov 2013to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- between the ages of 18 and 30 years
- comfortable reading in English
- normal visual acuity or corrected vision
- normal or corrected hearing.
- between the ages of 18 and 50 years
- comfortable reading in English
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- 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.
Who cannot join
- 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)
Show all 17Show fewer
- having consumed alcohol in the 24 hours prior to the first lab visit
- known allergy to any antibiotics.
- 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
About this study
Official title: The Effects of D-cycloserine on Neuroplasticity and Working Memory in Healthy Adults and Patients With Schizophrenia
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.
Read the 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).
- Conditions
- Schizophrenia
- Being tested
- D-cycloserine, Placebo
- Keywords
- Receptors, N-Methyl-D-Aspartate
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
100 mg D-cycloserine administered orally as encapsulated pill
PlaceboOther
Placebo administered orally as encapsulated pill
| Study group | Role | What they receive |
|---|---|---|
| Healthy Adult - Placebo | Placebo comparator | Single dose placebo pill in healthy adults Receives: Other: Placebo |
| Healthy Adult - D-cycloserine | Experimental | Single 100 mg dose D-cycloserine pill in healthy adults Receives: Drug: D-cycloserine |
| Schizophrenia - Placebo | Placebo comparator | Single dose placebo pill in schizophrenia patients Receives: Other: Placebo |
| Schizophrenia - D-cycloserine | Experimental | Single 100 mg dose D-cycloserine pill in schizophrenia patients Receives: Drug: D-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2016 (estimated)
- Study startNov 2013
- Primary completionJul 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert F. Asarnow, Ph.D, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02769936
- Sponsor's protocol ID
- 13-000409
- Status last verified
- May 2016
- First submitted
- 10 May 2016
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of D-cycloserine on Neuroplasticity and Working Memory in Healthy Adults and Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT02769936
- Acronym / sponsor ID
- 13-000409
- Conditions
- Schizophrenia
- Keywords
- Receptors, N-Methyl-D-Aspartate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 12 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy Adult - Placebo | Placebo comparator | Other: PlaceboSingle dose placebo pill in healthy adults |
| Healthy Adult - D-cycloserine | Experimental | Drug: D-cycloserineSingle 100 mg dose D-cycloserine pill in healthy adults |
| Schizophrenia - Placebo | Placebo comparator | Other: PlaceboSingle dose placebo pill in schizophrenia patients |
| Schizophrenia - D-cycloserine | Experimental | Drug: D-cycloserineSingle 100 mg dose D-cycloserine pill in schizophrenia patients |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- between the ages of 18 and 30 years
- comfortable reading in English
- normal visual acuity or corrected vision
- normal or corrected hearing.
- between the ages of 18 and 50 years
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-cycloserine100 mg D-cycloserine administered orally as encapsulated pill | Drug | Healthy Adult - D-cycloserine, Schizophrenia - D-cycloserine |
| PlaceboPlacebo administered orally as encapsulated pill | Other | Healthy Adult - Placebo, Schizophrenia - Placebo |
Primary outcome
Performance on Information Integration Learning Task
Time frame: Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
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
Time frame: Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
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
Time frame: Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
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)
Time frame: Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing D-cycloserine in people with Schizophrenia, run by University of California, Los Angeles.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Performance on Information Integration Learning Task (time frame: Testing Day (i.e. approx 3-5 hrs following placebo or D-cycloserine administration)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2016.