A RANDOMIZED PLACEBO-CONTROLLED STUDY OF LOVASTATIN (TM) IN CHILDREN WITH

洛伐他汀 (TM) 在患有以下疾病的儿童中的随机安慰剂对照研究

• 批准号: 8167315
• 负责人: Roger Packer
• 金额: $ 0.54万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167315
• 关键词: Adult; Attention; Biochemical; Child; Childhood; Clinical Trials; Cognitive; Cognitive deficits; Complication; Computer Retrieval of Information on Scientific Projects Database; Defect; Double-Blind Method; Funding; Grant; Hippocampus (Brain); Individual; Institution; Learning; Lovastatin; Measures; Memory; Mus; Neurologic; Performance; Pharmacological Treatment; Phase I Clinical Trials; Phase II Clinical Trials; Physiologic pulse; Placebos; Randomized; Reporting; Research; Research Personnel; Resources; Source; Therapeutic Intervention; United States National Institutes of Health; Visuospatial; arm; base; cognitive function; cohort; improved; morris water maze; mouse model; randomized placebo controlled trial

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The most common neurological complication of NF1 in childhood is cognitive deficits for which there are not effective specific pharmacological treatments. Studies indicate that LovastatinTM can reverse the biochemical, electrophysiological and cognitive deficits observe in Nf1 +/- mice to levels comparable to wild-type control mice. Nf1+/- mice treated with LovastatinTM demonstrated improved performance on tasks of spatial learning and memory (as measured by the Morris Water maze), attention, and pre-pulse inhibition. These tasks are hypothesized to reflect the cognitive deficits observed in children with NF1. The Morris Water Maze involves mechanisms of learning and memory, which relies on hippocampal functioning. While visual-spatial deficits have been reported in children with NF1 (e.g. Skirmisher, Billingsley, Slopes & Moore, 2003), no studies have reported on the visual spatial learning abilities in this cohort. LovastatinTM, which targets the inhibition of ras, is a logical choice as a potential therapeutic intervention for children with NF1 and cognitive deficits. Clinical trials indicate that LovastatinTM is effective and safe to treat heFH in adults and children. Results from a recently completed Phase I trial indicate that LovastatinTM is safe to be used in children (10-17 years) with NF1 (Acosta et al., 2007). Currently, no studies have examined the effect of LovastatinTM on cognitive functioning in individuals with NF1. This study will determine the efficacy of LovastatinTM as a treatment for the cognitive defects observed in children with NF1. We will conduct a multi-centre randomized, double-blind, Phase II trial with two treatment arms (LovastatinTM/placebo) for 16 weeks. Based on predictions from the NF1 murine mouse model, it is expected that children with NF1, who are impaired on a visual spatial learning task and/or an attention task, will benefit from LovastatinTM.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 NF1在童年时期最常见的神经系统并发症是认知缺陷，没有有效的特定药理治疗。研究表明，LovastatIntm可以将NF1 +/-小鼠观察到的生化，电生理和认知缺陷逆转至与野生型对照小鼠相当的水平。 用lovastatIntm治疗的NF1 +/-小鼠在空间学习和记忆任务（通过Morris Water Maze衡量），注意力和脉冲前抑制作用表现出改善的表现。 假设这些任务反映了NF1儿童中观察到的认知缺陷。 莫里斯水迷宫涉及学习和记忆的机制，这取决于海马功能。 虽然NF1儿童已经报道了视觉空间缺陷（例如Skimisher，Billingsley，Slopes＆Moore，2003年），但尚无关于此同类群体视觉空间学习能力的研究。 靶向抑制RA的LovastatIntm是对NF1和认知缺陷儿童的潜在治疗干预措施的逻辑选择。 临床试验表明，LovastatIntm在成人和儿童中可以有效且安全地治疗HEFH。 最近完成的I期试验的结果表明，LovastatIntm可以安全地用于儿童（10-17岁），使用NF1（Acosta等，2007）。 目前，尚无研究检查LovastatIntm对NF1个体认知功能的影响。这项研究将确定LovastatIntm作为在NF1儿童中观察到的认知缺陷的治疗方法的疗效。我们将使用两个治疗臂（LovastatIntm/安慰剂）进行16周的多中心随机，双盲，II期试验。基于NF1鼠标模型的预测，预计在视觉空间学习任务和/或注意力任务上受到损害的NF1儿童将从lovastatIntm中受益。