Schizophrenia
Conditions
Keywords
cognitive remediation
Brief summary
The investigators will test the effects of 3 days of D-serine (DSR) on auditory plasticity in a sensory based remediation (SBR) paradigm
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
Interventions
DRUGD-serine
D-serine 60 mg/kg
Sponsors
Nathan Kline Institute for Psychiatric Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mismatch Negativity (MMN) | 3 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tone Matching Threshold | three weeks | 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 |
Countries
United States
Participant flow
Pre-assignment details
Please see NCT01474395 for a related parallel study involving 13 schizophrenia patients and 13 healthy controls. Participants in NCT01474395 were not enrolled in the current study, i.e., both studies included separate groups of participants
Participants by arm
| Arm | Count |
|---|---|
| D-serine D-serine
D-serine: D-serine 60 mg/kg | 5 |
| No Intervention | 3 |
| Total | 8 |
Baseline characteristics
| Characteristic | D-serine | No Intervention | Total |
|---|---|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 9.4 | 45.4 years STANDARD_DEVIATION 14.3 | 44.0 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 0 / 5 | 0 / 3 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 |
Outcome results
Primary
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.
Time frame: 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine | Mismatch Negativity (MMN) | .086 micro volts | Standard Deviation 0.36 |
| no Intervention | Mismatch Negativity (MMN) | 0.31 micro volts | Standard Deviation 0.29 |
Secondary
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
Time frame: three weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine | Tone Matching Threshold | 11 percentage of difference in pitch | Standard Deviation 3.6 |
| no Intervention | Tone Matching Threshold | 2.3 percentage of difference in pitch | Standard Deviation 0.7 |