HDAC Inhibitor Augmentation to Clozapine
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
The main goal of this pilot study is to test the extent to which adjunctive treatment with the histone deacetylase (HDAC) inhibitor vorinostat improves brain plasticity and cognition in a pilot placebo-controlled trial in patients with schizophrenia who are on clozapine.
详细描述
The goal of this study is to perform a pilot clinical study with a small sample of subjects to evaluate the safety and tolerability of vorinostat when combined with clozapine treatment in patients with schizophrenia. The investigators will also evaluate the potential translation of our preclinical data into a clinical use of vorinostat for cognitive impairment in clozapine-treated schizophrenic patients.
Potential participants will be receiving stables doses of clozapine for a minimum period of 6 months before entry into the study. Clozapine was selected because i) the majority of our studies in mouse models were performed after chronic treatment with this atypical antipsychotic, and ii) the investigators' data in postmortem human brain samples of subjects with antemortem diagnosis of schizophrenia suggest up-regulation of HDAC2 in frontal cortex of schizophrenic subjects treated with atypical, but not typical, antipsychotic drugs.
The HDAC inhibitor vorinostat was selected because preliminary data suggest that chronic treatment with vorinostat improves HDAC2-dependent cognitive function in rodent models. Additionally, vorinostat is the first HDAC inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of cutaneous T-cell lymphoma. Dose(s) of vorinostat have been selected based on previous clinical studies in such patients with brain metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with DSM-5 Schizophrenia
- •Receiving stable dose pf clozapine (≥ 300 mg per day) for at least 6 months before entering the study
排除标准
- •Taking specific psychotropic medications (lamotrigine and valproic acid)
- •Current or recent (12-months) substance use or induced disorder
- •History of significant neurological or medical disorders
- •Intellectual disability
- •Known contraindications to the administration of vorinostat per product labeling
- •Women currently pregnant, planning to become pregnant, or receiving hormone therapy and refusing any form of birth control
研究组 & 干预措施
Vorinostat Group 1 (P-V-P-P)
This group will receive this sequence after the 1 initial week washout:
vorinstat (4 weeks) placebo (1 week) placebo (4 weeks)
干预措施: Vorinostat Oral Capsule Group 1 (Drug)
Vorinostat Group 2 (P-P-P-V)
This group will receive this sequence after the 1 initial week washout:
placebo (4 weeks) placebo (1 week) vorinostat (4 weeks)
干预措施: Vorinostat Oral Capsule Group 2 (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
时间窗: 10 weeks
Safety of vorinostat measured by number of adverse events
Change in clinical cognitive symptoms during adjunctive vorinostat therapy in schizophrenia patients treated with clozapine
时间窗: Baseline, Visit 4 (end of first intervention group/week 4), Visit 7 (end of study/10 weeks)
Participants will be given a cognitive test to assess executive function and speed.
次要结局
未报告次要终点