Rasagiline in the Treatment of Persistent Negative Symptoms of Schizophrenia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 4
- 主要终点
- Cognitive Testing - Probabilistic Learning Task
研究概览
简要总结
This is a study of a new medication for the treatment of cognitive impairments (thinking difficulties) and negative symptoms in people with schizophrenia. The new medication is rasagiline. Rasagiline is a drug which has been approved by the Food and Drug Administration for the treatment of Parkinson's disease. It is used to treat cognitive problems.
详细描述
The study will consist of two phases: a 4-week continued stability phase (lead-in phase) and a 12-week double-blind treatment phase. In the lead-in phase, subjects receiving antipsychotic medication, who manifest moderate to severe and persistent negative symptoms, will remain on their maintenance regimen for at least four weeks. The treatment phase will be a 12-week, parallel groups, double-blind, placebo-controlled trial of adjunctive rasagiline (1 mg/day), a selective MAO-B oxidase inhibitor.
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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will meet DSM-IV criteria for schizophrenia or schizoaffective disorder.
- •Current treatment with one or more second generation antipsychotics, except ziprasidone
- •On same second generation antipsychotic(s)for at least 56 days
- •On same dose of second generation antipsychotic(s)for at least 30 days
- •22-item SANS: Total score (i.e.all items minus global items and poverty of content of speech)greater than 20 or global Rating of Affective Flattening greater than or equal to 3 or global Rating of alogia greater than or equal to 3
- •BPRS: Sum of the four positive symptom items less than or equal to 16 (items 4,11,12,15)
- •BPRS: Sum of the four Anxiety/Depression Factor items less than or equal to 14 (items 1,2,5,9)
- •Simpson-Angus Scale: Total score less than or equal to 8
排除标准
- •DSM-IV Major Depressive Disorder within last 6 months
- •Current treatment with ziprasidone
- •DSM-IV diagnosis of alcohol or substance dependence within the last 6 months
- •DSM-IV criteria for alcohol or substance abuse within the last month
- •evidence of illicit substance use, as identified with urine toxicology screen
- •History of an organic brain disorder, mental retardation,epilepsy, or a medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol. See those listed below
- •Uncontrolled hypertension defined as BP exceeding 145/90 on 3 consecutive readings despite adequate treatment, pheochromocytoma, melanoma, hepatic insufficiency
- •Pregnancy or lactation in females
- •Pheochromocytoma
- •Hepatic insufficiency
研究组 & 干预措施
Rasagiline
Treatment with Rasagiline
干预措施: rasagiline (Pharmacodynamics) (Drug)
Inactive pill
Treatment with Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Cognitive Testing - Probabilistic Learning Task
时间窗: Beginning of treatment phase (week 0) and end of treatment phase (week 12)
To assess reward learning, participants used performance feedback to choose the most frequently rewarded item in each of three pairs of stimuli (one pair had reward probabilities: 80% vs 20%; one pair had reward probabilities of 70% vs 30%; one pair had the probabilities of 60% vs 40 %) (PL; Frank et al, 2004). A total of 240 trials were administered so each pair was seen 80 times. Higher scores represent more frequent choices of the optimal stimulus in each pair. The frequencies with which participants repeated an item choice that was rewarded on the previous presentation (win-stay) is also presented as a percentage. Similarly, the lose-shift score is the percentage of times that participants changed their choice for unrewarded items (lose-shift). The win-stay score serves as a measure of the impact of positive feedback on subsequent choices while the lost-shift score serves as a measure of the impact of negative feedback on subsequent choices.
Change in Negative Symptoms
时间窗: Every 4 weeks over a 12 week period
The Scale for the Assessment of Negative Symptoms (SANS) rating scale was used to assess the negative symptoms of schizophrenia. Scores on the subscales are combined (summed) to compute a total score. There are a total of 17 subscales. Each subscale ranges from 0="Not at all" to 5="Severe". Every 4 weeks the summed subscale scores provide a total score for that week (0-85). Higher scores indicate more severe negative symptoms.
Cognitive Testing - Delayed Discounting
时间窗: Beginning of treatment phase (week 0) and end of treatment phase (week 12)
The monetary choice questionnaire for hypothetical monetary rewards was used to assess delayed discounting (Kirby et al, 1999). The measure includes 27 items in which participants choose between a smaller, immediate reward (SIR) and a larger, delayed reward (LDR). There are three LDR sizes: small ($25-35), medium ($50-60) and large ($75-85). By examining the pattern of choices that participants make across the set of 27 items it is possible to calculate their delay discounting rate, termed K. The discount rate determines the steepness of the reduction in the present value of a reward with increases in the delay to the possible receipt of that reward. Thus, higher values in K represent greater discounting of the value of future rewards. With this measure K values can range between a low of 0.00016 to a high of 0.25. Higher K values have been linked to measures of impulsivity. Shown in the table are the K values observed when the future rewards were small, medium, or large.
Cognitive Testing - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score
时间窗: Beginning of treatment phase (week 0) and end of treatment phase (week 12)
The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160.
Cognitive Testing - N-Back Neurocognitive Task
时间窗: Beginning of treatment phase (week 0) and end of treatment phase (week 12)
The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.
次要结局
- Extrapyramidal Symptoms(Baseline (Week 0) and End of Study (Week 12))
- Number of Participants Exhibiting Side Effects(Every week for 12 weeks)
- Number of Participants With Akathisia(Baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks.)
- Change in Persistent Positive Symptoms(Every 4 weeks for 12 weeks.)
- Depressive Symptoms(Every 4 weeks for 12 weeks.)
- Global Change in Illness Severity(Every 4 weeks for 12 weeks.)
研究者
Robert Buchanan
Chief, Maryland Psychiatric Research Center, Outpatient Research Program
University of Maryland, Baltimore