A Placebo-controlled Trial of D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
研究概览
简要总结
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.
详细描述
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:
- D-cycloserine will significantly improve cognitive performance as measured by the composite score on the MATRICS battery compared to placebo after 8 weeks of cognitive remediation.
- D-cycloserine will significantly improve negative symptoms as measured by the SANS compared to placebo after 8 weeks when combined with cognitive remediation.
- D-cycloserine will significantly improve measures of functioning (GAS, QoL and CGI) at 8 weeks compared to placebo when combined with cognitive remediation.
- D-cycloserine effects on cognition, negative symptoms and functioning will persist compared to placebo when assessed at 6-month follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female
- •Age 18-65 years
- •Diagnosis of schizophrenia or schizoaffective disorder, depressed type
- •Stable dose of antipsychotic for at least 4 weeks
- •Able to provide informed consent
- •Able to complete a cognitive battery
- •Able to perform the cognitive remediation exercises
排除标准
- •Current treatment with clozapine
- •Seizure disorder
- •Unstable medical illness
- •Renal insufficiency measured as eGFR >60mg/dL/min
- •Active substance abuse: positive urine toxic screen
- •Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
研究组 & 干预措施
D-cycloserine
Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
干预措施: D-cycloserine (Drug)
D-cycloserine
Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
干预措施: Cognitive Remediation (Behavioral)
Placebo
Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
干预措施: Placebo (Drug)
Placebo
Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
干预措施: Cognitive Remediation (Behavioral)
结局指标
主要结局
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
时间窗: Baseline vs. Week 8
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.
Scale for Assessment of Negative Symptoms (SANS)
时间窗: Baseline vs. Week 8
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.
Auditory Discrimination Task: Interstimulus Interval (ISI)
时间窗: Baseline vs. Week 8
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.
次要结局
- Calgary Depression Scale for Schizophrenia (CDSS)(Baseline)
- Clinical Global Impression (CGI)(Weeks 0 and 8, and Month 6 after cognitive remediation completion)
- Side Effects Checklist (SEC)(Weeks 0 - 8, and Month 6 after cognitive remediation completion)
- Positive and Negative Syndrome Scale (PANSS)(Baseline)
- Global Assessment of Functioning Scale (GAS)(Baseline)
- Heinrich Quality of Life Scale (QoL)(Baseline)
研究者
Donald C. Goff, MD
Director of the Schizophrenia Clinical and Research Program
Massachusetts General Hospital