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| ID | Type | Description | Link |
|---|---|---|---|
| 5P50MH060450 | U.S. NIH Grant/Contract | View source | |
| DATR A3-NSC |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study seeks to examine the effects of D-cycloserine augmentation on cognitive remediation for patients diagnosed with schizophrenia. We will test the hypotheses that D-cycloserine will significantly improve cognitive performance, negative symptoms, and measures of functioning compared to placebo when combined with eight weeks of cognitive remediation. We expect that these effects will persist when assessed at six-month follow up.
D-cycloserine has been shown to enhance learning in animal models and, in a previous trial, once-weekly D-cycloserine improved negative symptoms in schizophrenia subjects. We set out to test whether DCS combined with cognitive remediation would improve learning of a practiced auditory discrimination task and whether gains would generalize to unpracticed cognitive tasks.
The proposed study consists of an 8-week, placebo-controlled, double-blind, parallel-group trial of D-cycloserine augmentation of cognitive remediation in schizophrenia outpatients. The primary outcome measure is change in performance on the MATRICS cognitive battery composite score after 8 weeks. Secondary outcome measures include a measure of processing speed assessed after weeks 1, 2, 4 & 8, and changes in negative symptoms and measures of functioning after 4 and 8 weeks. In addition, all outcome measures will be repeated at 6 months to assess persistence of benefit.
Hypotheses:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| D-cycloserine | Experimental | Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
|
| Placebo | Placebo Comparator | Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| D-cycloserine | Drug | 50 mg by mouth one hour before first cognitive remediation session each week for eight weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) | Change of a composite score from baseline to week 8 on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). The MATRICS consists of 10 cognitive tasks that are used to calculate scores in 7 cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores on each cognitive task are transformed on a normative scale into t-scores, and then these scores are combined to calculate the domain scores. The composite score is calculated by averaging all domain t-scores to come up with one overall cognitive composite t-score. For all scores on the assessment, the higher the score the better the performance on the task. | Baseline vs. Week 8 |
| Scale for Assessment of Negative Symptoms (SANS) | The total scores from baseline and 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 sub-scale total scores. Scores are reported for baseline and week 8. | Baseline vs. Week 8 |
| Auditory Discrimination Task: Interstimulus Interval (ISI) | The auditory discrimination task involved trials in which the subject differentiated between rapidly-presented frequency-modulated sweeps separated by a short interstimulus interval (ISI). In this task, sustained successful performance is more difficult with shorter stimulus presentations and ISIs (which were equal within a trial). Thus, our dependent measure was the shortest stimulus duration/ISI, in ms, for trials in which subjects were able to perform the task at 85% accuracy, referred to as ISI for simplicity. The shorter the score the better the performance on the task. Scores are reported for baseline and week 8. | Baseline vs. Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Positive and Negative Syndrome Scale (PANSS) | The baseline score 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. The higher a score the more prominent a positive symptom is. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Donald C. Goff, M.D. | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24485587 | Result | Cain CK, McCue M, Bello I, Creedon T, Tang DI, Laska E, Goff DC. d-Cycloserine augmentation of cognitive remediation in schizophrenia. Schizophr Res. 2014 Mar;153(1-3):177-83. doi: 10.1016/j.schres.2014.01.016. Epub 2014 Jan 30. |
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54 patients were assessed for eligibility; however, 14 were excluded (11 were ineligible, and 3 withdrew consent). 40 participants were randomized, however 4 were excluded (1 serious adverse event, 2 withdrew consent, and 1 was lost to follow up), therefore 36 entered the treatment phase.
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| ID | Title | Description |
|---|---|---|
| FG000 | D-cycloserine | Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
| FG001 | Placebo | Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | D-cycloserine | Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
| BG001 | Placebo | Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) | Change of a composite score from baseline to week 8 on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). The MATRICS consists of 10 cognitive tasks that are used to calculate scores in 7 cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores on each cognitive task are transformed on a normative scale into t-scores, and then these scores are combined to calculate the domain scores. The composite score is calculated by averaging all domain t-scores to come up with one overall cognitive composite t-score. For all scores on the assessment, the higher the score the better the performance on the task. | 18 participants in each arm had baseline values available for analysis. 17 in the D-cycloserine arm and 15 in the placebo arm had week 8 values available for analysis. | Posted | Mean | Standard Deviation | t-scores | Baseline vs. Week 8 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | D-cycloserine | Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. D-cycloserine: 50 mg by mouth one hour before first cognitive remediation session each week for eight weeks. Cognitive Remediation: 40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Psychiatric disorders | Patient was hospitalized due to worsening psychiatric symptoms. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Donald C Goff | Nathan Klein Institute for Psychiatric Research | 646-754-4843 | donald.goff@nyumc.org |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D060825 | Cognitive Dysfunction |
| D001523 | Mental Disorders |
| D011618 | Psychotic Disorders |
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| D003523 | Cycloserine |
| D000072466 | Cognitive Remediation |
| ID | Term |
|---|---|
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo by mouth one hour before first cognitive remediation session each week for eight weeks. |
|
| Cognitive Remediation | Behavioral | 40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks. |
|
|
| Baseline |
| Global Assessment of Functioning Scale (GAS) | The Global Assessment of Functioning Scale (GAS) measured at baseline. This scale measures social, occupational, and psychological functioning, on a scale of 0-100. The higher the score, the greater a participant's functioning level. | Baseline |
| Heinrich Quality of Life Scale (QoL) | Baseline scores of the Heinrich Quality of Life Scale, a 21 item scale designed and validated to measure intrapsychic foundations, interpersonal relations, instrumental role, and common objects and activities in patients diagnosed with Schizophrenia. Patients are rated on each of the 21 items on a scale of 0-6. Total scores are computed by adding up the scores of each individual item, with a total score ranging from 0-126. Higher scores reflect higher functioning. | Baseline |
| Calgary Depression Scale for Schizophrenia (CDSS) | Baseline scores on the Calgary Depression Scale for Schizophrenia (CDSS). Total CDSS scores range from 0-27. The assessment is comprised of 9 questions covering the topics of Depression, Hopelessness, Self Depreciation, Guilty Ideas of Reference, Pathological Guilt, Morning Depression, Early Wakening, Suicide, Observed Depression. Each item is scored on a scale from 0-3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The total score is computed by adding up the individual scores of each item. The higher the score, the more prominent the symptoms of depression are for the participant. | Baseline |
| Clinical Global Impression (CGI) | Considering you total clinical experience with this patient population, how mentally ill is the patient at this time? 1=Normal, not at all, 2=Borderline mentally ill, 3=Mildy ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, 7=Among the most extremely ill patients; a higher score indicates worse outcome | Weeks 0 and 8, and Month 6 after cognitive remediation completion |
| Side Effects Checklist (SEC) | Each side effect is entered as either yes or no for having had any severity of the side effect at each visit. | Weeks 0 - 8, and Month 6 after cognitive remediation completion |
| Changed antipsychotic |
|
| Lost to Follow-up |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | D-cycloserine | Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
| OG001 | Placebo | Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. |
|
|
| Primary | Scale for Assessment of Negative Symptoms (SANS) | The total scores from baseline and 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 sub-scale total scores. Scores are reported for baseline and week 8. | 18 participants in each arm had baseline values available for analysis. 17 in the D-cycloserine arm and 15 in the placebo arm had week 8 values available for analysis. | Posted | Mean | Standard Deviation | units on a scale | Baseline vs. Week 8 |
|
|
|
| Primary | Auditory Discrimination Task: Interstimulus Interval (ISI) | The auditory discrimination task involved trials in which the subject differentiated between rapidly-presented frequency-modulated sweeps separated by a short interstimulus interval (ISI). In this task, sustained successful performance is more difficult with shorter stimulus presentations and ISIs (which were equal within a trial). Thus, our dependent measure was the shortest stimulus duration/ISI, in ms, for trials in which subjects were able to perform the task at 85% accuracy, referred to as ISI for simplicity. The shorter the score the better the performance on the task. Scores are reported for baseline and week 8. | 18 participants in each arm had baseline values available for analysis. 17 in the D-cycloserine arm and 15 in the placebo arm had week 8 values available for analysis. | Posted | Mean | Standard Deviation | milliseconds | Baseline vs. Week 8 |
|
|
|
| Secondary | Positive and Negative Syndrome Scale (PANSS) | The baseline score 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. The higher a score the more prominent a positive symptom is. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Global Assessment of Functioning Scale (GAS) | The Global Assessment of Functioning Scale (GAS) measured at baseline. This scale measures social, occupational, and psychological functioning, on a scale of 0-100. The higher the score, the greater a participant's functioning level. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Heinrich Quality of Life Scale (QoL) | Baseline scores of the Heinrich Quality of Life Scale, a 21 item scale designed and validated to measure intrapsychic foundations, interpersonal relations, instrumental role, and common objects and activities in patients diagnosed with Schizophrenia. Patients are rated on each of the 21 items on a scale of 0-6. Total scores are computed by adding up the scores of each individual item, with a total score ranging from 0-126. Higher scores reflect higher functioning. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Calgary Depression Scale for Schizophrenia (CDSS) | Baseline scores on the Calgary Depression Scale for Schizophrenia (CDSS). Total CDSS scores range from 0-27. The assessment is comprised of 9 questions covering the topics of Depression, Hopelessness, Self Depreciation, Guilty Ideas of Reference, Pathological Guilt, Morning Depression, Early Wakening, Suicide, Observed Depression. Each item is scored on a scale from 0-3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The total score is computed by adding up the individual scores of each item. The higher the score, the more prominent the symptoms of depression are for the participant. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Clinical Global Impression (CGI) | Considering you total clinical experience with this patient population, how mentally ill is the patient at this time? 1=Normal, not at all, 2=Borderline mentally ill, 3=Mildy ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, 7=Among the most extremely ill patients; a higher score indicates worse outcome | 18 participants in each arm had baseline data available for analysis. At week 8, 17 participants in the D-cycloserine group and 15 in the placebo group had data available. At month 6, 6 participants in the D-cycloserine group and 4 in the placebo group had data available. | Posted | Mean | Standard Deviation | units on a scale | Weeks 0 and 8, and Month 6 after cognitive remediation completion |
|
|
|
| Secondary | Side Effects Checklist (SEC) | Each side effect is entered as either yes or no for having had any severity of the side effect at each visit. | 18 participants in each arm had baseline data available for analysis. At week 8, 17 participants in the D-cycloserine group and 15 in the placebo group had data available. At month 6, 6 participants in the D-cycloserine group and 4 in the placebo group had data available. | Posted | Count of Participants | Participants | Weeks 0 - 8, and Month 6 after cognitive remediation completion |
|
|
|
| 1 |
| 18 |
| 17 |
| 18 |
| EG001 | Placebo | Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks. Placebo: Placebo by mouth one hour before first cognitive remediation session each week for eight weeks. Cognitive Remediation: 40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks. | 0 | 18 | 13 | 18 |
| Diarrhea | Gastrointestinal disorders |
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| Drowsiness | General disorders |
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| Hypertension | Cardiac disorders |
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| Hypotension | Cardiac disorders |
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| Infection | Infections and infestations |
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| Insomnia | General disorders |
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| Tachycardia | Cardiac disorders |
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| D023303 |
| Oxazolidinones |
| D010080 | Oxazoles |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
| Week 8 |
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| Week 8 |
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| Week 8 |
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| Month 6 |
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| No |
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| Baseline : Rash |
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| Baseline : Urticaria (Hives, Itching) |
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| Baseline : Blurred Vision |
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| Baseline : Sedation/Drowsiness |
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| Baseline : Restlessness |
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| Baseline : Insomnia |
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| Baseline : Malaise |
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| Baseline : Stiffness |
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| Baseline : Tremor |
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| Baseline : Dizziness |
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| Baseline : Headache |
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| Baseline : Fever |
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| Baseline : Sore Throat |
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| Baseline : Dry Mouth |
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| Baseline : Hypersalivation |
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| Baseline : Enuresis |
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| Baseline : Constipation |
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| Baseline : Diarrhea |
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| Baseline : Anorexia |
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| Baseline : Nausea |
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| Baseline : Vomiting |
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| Baseline : Menstrual Irregularities |
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| Baseline : Breast Tenderness/Galactorrhea |
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| Week 8 : Bruising easily |
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| Week 8 : Rash |
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| Week 8 : Urticaria (Hives, Itching) |
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| Week 8 : Blurred Vision |
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| Week 8 : Sedation/Drowsiness |
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| Week 8 : Restlessness |
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| Week 8 : Insomnia |
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| Week 8 : Malaise |
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| Week 8 : Stiffness |
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| Week 8 : Tremor |
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| Week 8 : Dizziness |
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| Week 8 : Headache |
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| Week 8 : Fever |
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| Week 8 : Sore Throat |
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| Week 8 : Dry Mouth |
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| Week 8 : Hypersalivation |
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| Week 8 : Enuresis |
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| Week 8 : Constipation |
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| Week 8 : Diarrhea |
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| Week 8 : Anorexia |
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| Week 8 : Nausea |
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| Week 8 : Vomiting |
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| Week 8 : Menstrual Irregularities |
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| Week 8 : Breast Tenderness/Galactorrhea |
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| Month 6 : Bruising easily |
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| Month 6 : Rash |
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| Month 6 : Urticaria (Hives, Itching) |
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| Month 6 : Blurred Vision |
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| Month 6 : Sedation/Drowsiness |
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| Month 6 : Restlessness |
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| Month 6 : Insomnia |
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| Month 6 : Malaise |
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| Month 6 : Stiffness |
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| Month 6 : Tremor |
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| Month 6 : Dizziness |
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| Month 6 : Headache |
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| Month 6 : Fever |
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| Month 6 : Sore Throat |
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| Month 6 : Dry Mouth |
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| Month 6 : Hypersalivation |
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| Month 6 : Enuresis |
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| Month 6 : Constipation |
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| Month 6 : Diarrhea |
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| Month 6 : Anorexia |
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| Month 6 : Nausea |
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| Month 6 : Vomiting |
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| Month 6 : Menstrual Irregularities |
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| Month 6 : Breast Tenderness/Galactorrhea |
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