Schizophrenia
Conditions
Keywords
schizophrenia, cognition, d-cycloserine, memory
Brief summary
The study aims to assess the effects of single dose and repeated weekly dosing of 50mg d-cycloserine versus placebo on cognitive and memory functioning in schizophrenia patients. The study will also examine the effects of 50mg d-cycloserine on positive symptoms and negative symptoms, as well as assess tolerability and side-effects.
Detailed description
This is a ten-week, parallel-group, placebo-controlled trial examining the cognitive effects at weeks 1, 2, 3. 4, 5, 6, 7, 8 & 10 of once-weekly oral D-cycloserine 50 mg added to a stable dose of antipsychotic for 8 weeks in 60 adult outpatients with schizophrenia. Specific aims: 1. Assess the effects of a single dose of D-cycloserine 50 mg on cognitive functioning compared to placebo. 2. Assess the effects of repeated weekly dosing of D-cycloserine on cognitive functioning at week 8 compared to placebo. 3. Assess the effects of repeated weekly dosing of D-cycloserine on memory functioning once a week 1 hour after medication administration compared to placebo. 4. Assess the persistence of learned information in a no-treatment follow-up assessment at Week 10 in the D-cycloserine group compared to the placebo group. 5. Assess effects of weekly D-cycloserine dosing on positive & negative symptoms at week 8 compared to placebo. 6. Assess tolerability and side effects of weekly D-cycloserine compared to placebo. 7. Assess the effects of d-cycloserine dosed weekly for seven weeks on reward responsiveness as measured with the response bias task compared with placebo. 8. Assess the effects of d-cycloserine dosed weekly for seven weeks on measures of functioning.
Interventions
DRUGd-cycloserine
50mg dose d-cycloserine v placebo
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 2. Age 18-65 years 3. Diagnosis of schizophrenia or schizoaffective disorder, depressed type 4. Stable dose of antipsychotic for at least 4 weeks. 5. Able to provide informed consent 6. Able to complete a cognitive battery
Exclusion criteria
1. Current treatment with clozapine 2. Dementia 3. Seizure disorder 4. Unstable medical illness 5. Active substance abuse 6. Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main Outcome Measure: The Change From Baseline to Week 8 on the SANS | Baseline score vs. Week 8 | The change from baseline to week 8 on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The total score was computed by adding all the subscale total scores. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Effects on the Positive Syndrome Subscale of the PANSS | Baseline score vs. Week 8 score | The change from baseline to week 8 on the positive symptom sub-scale of the Positive and Negative Syndrome Scale (PANSS). Total PANSS positive symptom sub-scale scores range from 7-49. The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. A score of one on each item 1 absent, 2 is minimal, 3 is mild, 4 is moderate, 5 is moderately severe, 6 is severe, and 7 is extreme. The total score was computed by adding all the items on the sub-scale together. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score). |
Countries
United States
Participant flow
Recruitment details
Participants were stable adult outpatients at an urban community mental health center, ages 18-65 years, with a diagnosis of schizophrenia .
Participants by arm
| Arm | Count |
|---|---|
| D-cycloserine 50 mg d-cycloserine | 19 |
| Placebo 50 mg placebo | 19 |
| Total | 38 |
Baseline characteristics
| Characteristic | Total | D-cycloserine | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 19 Participants | 19 Participants |
| Age, Continuous | 49.05 years STANDARD_DEVIATION 7.905 | 50.1 years STANDARD_DEVIATION 9.15 | 48 years STANDARD_DEVIATION 6.66 |
| Region of Enrollment United States | 38 participants | 19 participants | 19 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 23 Participants | 10 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 19 | 13 / 19 |
| serious Total, serious adverse events | 1 / 19 | 0 / 19 |
Outcome results
Primary
Main Outcome Measure: The Change From Baseline to Week 8 on the SANS
The change from baseline to week 8 on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The total score was computed by adding all the subscale total scores. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score).
Time frame: Baseline score vs. Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-cycloserine | Main Outcome Measure: The Change From Baseline to Week 8 on the SANS | 2.06 Units on a scale | Standard Deviation 5.03 |
| Placebo | Main Outcome Measure: The Change From Baseline to Week 8 on the SANS | -2.11 Units on a scale | Standard Deviation 7.05 |
Secondary
Treatment Effects on the Positive Syndrome Subscale of the PANSS
The change from baseline to week 8 on the positive symptom sub-scale of the Positive and Negative Syndrome Scale (PANSS). Total PANSS positive symptom sub-scale scores range from 7-49. The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. A score of one on each item 1 absent, 2 is minimal, 3 is mild, 4 is moderate, 5 is moderately severe, 6 is severe, and 7 is extreme. The total score was computed by adding all the items on the sub-scale together. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score).
Time frame: Baseline score vs. Week 8 score
Population: One participant from the placebo group was removed from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-cycloserine | Treatment Effects on the Positive Syndrome Subscale of the PANSS | .19 PANSS Positive Subscale Units | Standard Deviation 2.1 |
| Placebo | Treatment Effects on the Positive Syndrome Subscale of the PANSS | -.19 PANSS Positive Subscale Units | Standard Deviation 4.65 |