A Placebo Controlled Trial of Glycine Added to Clozapine in Schizophrenia
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Change in SANS Total Score from Baseline to Week 8
研究概览
简要总结
The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative symptoms (such as loss of interest, loss of energy, loss of warmth, and loss of humor) which occur between phases of positive symptoms (marked by hallucinations, delusions, and thought confusions) in schizophrenics.
Clozapine is currently the most effective treatment for negative symptoms of schizophrenia. Two other drugs, D-cycloserine and glycine, are being investigated as new treatments. D-cycloserine improves negative symptoms when added to some drugs, but may worsen these symptoms when given with clozapine. Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine. This study gives either D-cycloserine or glycine (or an inactive placebo) with clozapine to determine which is the best combination.
Patients will be assigned to 1 of 3 groups. Group 1 will receive D-cycloserine plus clozapine. Group 2 will receive glycine plus clozapine. Group 3 will receive an inactive placebo plus clozapine. Patients will receive these medications for 8 weeks. Negative symptoms of schizophrenia will be monitored through the Scale for the Assessment of Negative Symptoms, Positive symptoms will be monitored through the Positive and Negative Syndrome Scale, and additionally subjects will complete the Brief Psychiatric Rating Scale and the Global Assessment Scale.
An individual may be eligible for this study if he/she is 18 to 65 years old and has been diagnosed with schizophrenia.
详细描述
To determine if glycine produces improvement in negative symptoms and D-cycloserine produces worsening in symptoms compared to placebo, patients will undergo a double blind study of d-cycloserine and glycine treatment added to clozapine.
Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics, but the neurochemical actions contributing to this superior clinical efficacy remain unclear. Recent evidence points to a role for glutamatergic dysregulation in schizophrenia, as well as important differences between conventional agents and clozapine in effects upon glutamatergic systems. D-cycloserine, a partial agonist at the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor, improves negative symptoms when added to conventional agents and worsens negative symptoms when added to clozapine. High-dose glycine also improves negative symptoms and has provided preliminary evidence suggesting that glycine improves negative symptoms when added to clozapine. Serum concentrations of glycine predicted response to both high-dose glycine and D-cycloserine. Both clozapine and D-cycloserine may improve negative symptoms by activation of the glycine modulatory site of the NMDA receptor complex. Because D-cycloserine is a partial agonist, it may act as an antagonist at the glycine site in the presence of clozapine, whereas the full agonist, glycine, would not be expected to worsen negative symptoms in the presence of clozapine.
This study proposes to administer a fixed-dose of D-cycloserine, glycine, or placebo added to clozapine in 45 patients with schizophrenia. Because assessments are standardized between studies, results from this study can be compared with results from a previous study of D-cycloserine added to conventional neuroleptic.
The study was ultimately suspended before participants were enrolled, due to definitive findings indicating that pairing treatment of D-cycloserine with Clozapine resulted in worsening of negative symptoms.
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
- Triple (Participant, 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
- •Diagnosis of Schizophrenia
- •Score of 27 or greater on the Scale for the Assessment of Negative Symptoms (SANS)
- •Treatment with stable dose of clozapine for at least 4 weeks
- •Between 18 and 65 years old
排除标准
- •No other antipsychotic medications in oral for for at least 3 months or in depot form for 6 months
- •Current major depressive episode
- •Current substance abuse diagnosis
研究组 & 干预措施
Placebo
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of placebo powder in 7 ounces of lemonade twice a day in addition to clozapine treatment.
干预措施: Placebo (Drug)
Glycine
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of glycine in 7 ounces of lemonade twice a day in addition to clozapine treatment.
干预措施: Glycine (Drug)
Glycine
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of glycine in 7 ounces of lemonade twice a day in addition to clozapine treatment.
干预措施: Clozapine (Drug)
Placebo
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of placebo powder in 7 ounces of lemonade twice a day in addition to clozapine treatment.
干预措施: Clozapine (Drug)
D-Cycloserine
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with D-cycloserine in addition to clozapine treatment.
干预措施: D-cycloserine (Drug)
D-Cycloserine
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with D-cycloserine in addition to clozapine treatment.
干预措施: Clozapine (Drug)
结局指标
主要结局
Change in SANS Total Score from Baseline to Week 8
时间窗: Baseline, Week 8
次要结局
- Change in Positive and Negative Syndrome Score from Baseline to Week 8(Baseline, Week 8)
研究者
Donald C. Goff, MD
Director of the Schizophrenia Clinical and Research Program
Massachusetts General Hospital