Schizoaffective Disorder, Schizophrenia
Conditions
Brief summary
This study is based on the hypothesis that by increasing N-methyl-D-aspartic acid (NMDA) receptor function in the brain and thereby increasing the capacity of the brain to both form new connections and strengthen existing connections, schizophrenic patients may derive both greater and sustained benefit from cognitive retraining.
Detailed description
Patients with schizophrenia or schizoaffective disorder who are currently receiving antipsychotic medication will be randomly assigned in a double-blind manner to receive either D-serine (30 mg/kg) or placebo in addition to cognitive rehabilitation or a non-interactive placebo for 12 weeks.
Interventions
DRUGD-serine
D-serine (30 mg/kg)
BEHAVIORALCognitive Retraining (CRT)
Cognitive retraining therapy (CRT)
DRUGPlacebo
Placebo D-serine Drug
BEHAVIORALCognitive Retraining Placebo
Cognitive retraining therapy (CRT) control
Sponsors
National Alliance for Research on Schizophrenia and Depression
Donaghue Medical Research Foundation
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia or schizoaffective disorder Exclusion * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wisconsin Card Sorting Test (WCST) | 12 weeks | The WCST allows the clinician to speculate to the following frontal lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability. |
| Hopkins Verbal Learning Test | 12 weeks | The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24. |
| Spatial Span- Total Score | 12 weeks | The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28. |
| Positive and Negative Syndrome Scale (PANSS) | 12 weeks | The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Simpson-Angus Neurological Rating Scale | 12 weeks | Simpson-Angus Scale (SAS) is a 10-item rating scale that has been used widely for assessment in both clinical practice and research settings. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The highest possible score is 40. |
| UCSD Performance-Based Skills Assessment (UPSA) | 12 weeks | The UCSD Performance-Based Skills Assessment (UPSA) is a role-play test designed to evaluate a person's functional capacity in two selected areas of basic living skills. These areas include Finance and Communication. Subjects being tested utilize props to demonstrate how they perform everyday activities and are assessed on their actual performance. The higher the score, the better the performance of an individual. The scores range from 0 to 100. |
| Heinrichs-Carpenter Quality of Life Scale | 12 weeks | The Heinrichs-Carpenter Quality of Life Scale is a testing device. It has a range of possible scores, 0-126 used to evaluate social functioning & behavior in patients with schizophrenia-lower scores represent poorer mental health. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled between 2003 and 2008, with enrollment of subjects in India starting later (2005) and ending in 2008.
Pre-assignment details
132 subjects were screened for eligibility. After screening, eligible subjects were randomized to receive: D-serine+CRT, placebo D-serine+CRT, D-serine + control CRT, or placebo D-serine + control CRT. Randomization was stratified by screening performance IQ. Separate randomization schedules (block size= 4) were generated within IQ stratum.
Participants by arm
| Arm | Count |
|---|---|
| D-serine/Control D-serine/control
D-serine : D-serine (30 mg/kg) | 27 |
| Placebo/Cog Rehab Placebo/cog rehab
Cognitive retraining : Cog rehab | 27 |
| D-serine/Cog Rehab D-serine/cog rehab
D-serine : D-serine (30 mg/kg) | 24 |
| Placebo/Control Placebo/control
Cognitive retraining : Cog rehab | 26 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 10 | 9 | 9 |
Baseline characteristics
| Characteristic | D-serine/Control | Placebo/Cog Rehab | D-serine/Cog Rehab | Placebo/Control | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.7500 years STANDARD_DEVIATION 8.01889 | 34.4762 years STANDARD_DEVIATION 8.76139 | 36.3158 years STANDARD_DEVIATION 9.16547 | 34.4545 years STANDARD_DEVIATION 9.3642 | 35.21 years STANDARD_DEVIATION 8.72 |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 5 Participants | 7 Participants | 26 Participants |
| Sex: Female, Male Male | 18 Participants | 22 Participants | 19 Participants | 19 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 27 | 14 / 27 | 12 / 24 | 18 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 24 | 0 / 26 |
Outcome results
Primary
Hopkins Verbal Learning Test
The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | Hopkins Verbal Learning Test | 20.74 units on a scale | Standard Deviation 5.25 |
| Placebo/Cog Rehab | Hopkins Verbal Learning Test | 19.80 units on a scale | Standard Deviation 5.94 |
| D-serine/Cog Rehab | Hopkins Verbal Learning Test | 20.42 units on a scale | Standard Deviation 7.51 |
| Placebo/Control | Hopkins Verbal Learning Test | 21.45 units on a scale | Standard Deviation 5.85 |
Primary
Positive and Negative Syndrome Scale (PANSS)
The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | Positive and Negative Syndrome Scale (PANSS) | 53.30 units on a scale | Standard Deviation 13.58 |
| Placebo/Cog Rehab | Positive and Negative Syndrome Scale (PANSS) | 52.01 units on a scale | Standard Deviation 13.34 |
| D-serine/Cog Rehab | Positive and Negative Syndrome Scale (PANSS) | 53.79 units on a scale | Standard Deviation 12.76 |
| Placebo/Control | Positive and Negative Syndrome Scale (PANSS) | 53.96 units on a scale | Standard Deviation 12.43 |
Primary
Spatial Span- Total Score
The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | Spatial Span- Total Score | 13.59 units on a scale | Standard Deviation 4.18 |
| Placebo/Cog Rehab | Spatial Span- Total Score | 13.88 units on a scale | Standard Deviation 4.2 |
| D-serine/Cog Rehab | Spatial Span- Total Score | 13.21 units on a scale | Standard Deviation 3.23 |
| Placebo/Control | Spatial Span- Total Score | 13.58 units on a scale | Standard Deviation 4.07 |
Primary
Wisconsin Card Sorting Test (WCST)
The WCST allows the clinician to speculate to the following frontal lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | Wisconsin Card Sorting Test (WCST) | 38.43 percentage of correct responses | Standard Deviation 24.07 |
| Placebo/Cog Rehab | Wisconsin Card Sorting Test (WCST) | 35.79 percentage of correct responses | Standard Deviation 21.57 |
| D-serine/Cog Rehab | Wisconsin Card Sorting Test (WCST) | 43.14 percentage of correct responses | Standard Deviation 27.06 |
| Placebo/Control | Wisconsin Card Sorting Test (WCST) | 39.57 percentage of correct responses | Standard Deviation 22.31 |
Secondary
Heinrichs-Carpenter Quality of Life Scale
The Heinrichs-Carpenter Quality of Life Scale is a testing device. It has a range of possible scores, 0-126 used to evaluate social functioning & behavior in patients with schizophrenia-lower scores represent poorer mental health.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | Heinrichs-Carpenter Quality of Life Scale | 67.26 units on a scale | Standard Deviation 20.04 |
| Placebo/Cog Rehab | Heinrichs-Carpenter Quality of Life Scale | 68.30 units on a scale | Standard Deviation 25.59 |
| D-serine/Cog Rehab | Heinrichs-Carpenter Quality of Life Scale | 63.25 units on a scale | Standard Deviation 24.15 |
| Placebo/Control | Heinrichs-Carpenter Quality of Life Scale | 63.92 units on a scale | Standard Deviation 19.53 |
Secondary
Simpson-Angus Neurological Rating Scale
Simpson-Angus Scale (SAS) is a 10-item rating scale that has been used widely for assessment in both clinical practice and research settings. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The highest possible score is 40.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | Simpson-Angus Neurological Rating Scale | 1.41 units on a scale | Standard Deviation 2.53 |
| Placebo/Cog Rehab | Simpson-Angus Neurological Rating Scale | 0.72 units on a scale | Standard Deviation 1.73 |
| D-serine/Cog Rehab | Simpson-Angus Neurological Rating Scale | 1.04 units on a scale | Standard Deviation 1.27 |
| Placebo/Control | Simpson-Angus Neurological Rating Scale | 1.81 units on a scale | Standard Deviation 2.25 |
Secondary
UCSD Performance-Based Skills Assessment (UPSA)
The UCSD Performance-Based Skills Assessment (UPSA) is a role-play test designed to evaluate a person's functional capacity in two selected areas of basic living skills. These areas include Finance and Communication. Subjects being tested utilize props to demonstrate how they perform everyday activities and are assessed on their actual performance. The higher the score, the better the performance of an individual. The scores range from 0 to 100.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine/Control | UCSD Performance-Based Skills Assessment (UPSA) | 34.19 units on a scale | Standard Deviation 9.41 |
| Placebo/Cog Rehab | UCSD Performance-Based Skills Assessment (UPSA) | 32.80 units on a scale | Standard Deviation 10.98 |
| D-serine/Cog Rehab | UCSD Performance-Based Skills Assessment (UPSA) | 32.60 units on a scale | Standard Deviation 13.82 |
| Placebo/Control | UCSD Performance-Based Skills Assessment (UPSA) | 31.39 units on a scale | Standard Deviation 10.01 |