Phase 2B Trial of Memantine for the Treatment of Amyotrophic Lateral Sclerosis

美金刚治疗肌萎缩侧索硬化症的 2B 期试验

• 批准号: 10242456
• 负责人: Richard J. Barohn
• 金额: $ 10.58万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-17 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242456
• 关键词: Phase; 2B; Trial; Memantine; Treatment

Project Summary/Abstract Amyotropnic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 30,000 Americans each year. Of these 3O,OO0 Americans, it has been suggested that up to 50o/o will experience cognitive and behavioral changes in the form of frontotemporal dysfunction and up to +OZo will meet criteria for frontotemporal dementia (FTD) (42, 43). Riluzole the only FDA approved agent for ALS extends a patient's lifespan by 2-3 months, and there are flo proven therapies tor tne cognitive changes associated with ALS. More effective therapy for this universally fatal disease is desperately needed' Results from an open label pitot trial of 20 patients treated with memantine at 10 mg BID suggested that treatment with the combination of memantine and riluzole slowed ALS disease pro{ression (1). This trial also showed that levels of specific protein biomarkers in the CSF at b"s-etine correlated with the rate of disease progression. (1). A concurrent phase ll study performed by Dr Carvalho, found no effect with similar dosing(16); however, the study was iiriteO in terms of power. Comtnents on previous failed drug trials in ALS have raised the concern that many ALS trials study a potential therapeutic agent at only a single dose and thus may miss the potential efficacy of hon FDA approved d-oses; therefore, this proposed study will tesi a higher dose of memantine, 20 mg BlD, in a double blind, placebo controlled, randomized trial of g6 patients with ALS to determine if a combination therapy of memantine with riluzole can slow disease progression compared to treatment with riluzole alone. The primary outcome measure will be the rate of disease progression as measured by the ALS Functional Rating Scate- Revised (ALSFRS-R). ln addition we will examine the cognitive deficits seen in ALS patients measured by the ALS Cognitive Behavioral Screen (ALS-CBS) and the i.l"rropsychiatric lnventory Questionnaire (NlP-Q). Finally we will examine specific validated protein blomarkers found in the cerebrospinal fluid to determine if there is a correlation between ihe levels of these biomarkers and the rate of disease progression. ln particular we will measure the ratio of phosphorylated heavy neurofilament to Complement 3 (31) to see if this ratio is predictive of disease progression and if the levels change during therapy with memantine' ' This project witl otfer unique insights into this untreatable disease. lf this study confirms earlier results and suggests that memantine, when used in conjunction with riluzole, significantly slows down the progression of the disease, as well as ameliorates cognitive deficits in patients with fronto-temporaidysfunction, it will set the groundwork for conducting a larger phase lll trial'

项目摘要/摘要 肌肌肉横向硬化症（ALS）是一种致命的神经退行性疾病，会影响 每年30,000名美国人。在这些3o，OO0美国人中，有人建议高达50o/o 会在额颞功能障碍的形式中经历认知和行为变化 最多 +Ozo将符合额颞痴呆（FTD）的标准（42，43）。 riluzole唯一的FDA ALS的批准代理将患者的寿命延长了2-3个月，并且有经验证明 与ALS相关的认知变化的疗法。更有效的疗法 迫切需要普遍致命的疾病” 由20例以10 mg BID治疗的20例患者进行的开放标签皮托试验的结果 提出与美容和riluzole结合的治疗减慢了ALS疾病 pro {ression（1）。该试验还表明，CSF中特定蛋白质生物标志物的水平 b“ S- Etine与疾病进展率相关。（1）。 由Carvalho博士表演，发现没有类似给药的作用（16）；但是，这项研究是 在权力方面。 ALS以前的药物试验失败的comtnent提出了 担心许多ALS试验仅以一次剂量研究潜在的治疗剂，因此 可能会错过FDA批准的D-SOSS的潜在功效；因此，这项拟议的研究将 在双盲，安慰剂控制的，随机的 G6 ALS患者的试验，以确定美金刚与Riluzole的联合疗法是否 与单独使用瑞唑的治疗相比，疾病进展可以放缓。主要结果 量度将是通过ALS功能等级衡量的疾病进展率 分数修订（ALSFRS-R）。 LN补充我们将检查ALS中看到的认知缺陷 通过ALS认知行为筛查（ALS-CB）和 i.l“ rropsshientic lnventory问卷（NLP-Q）。最后，我们将检查经过特定验证的特定验证 在脑脊液中发现的蛋白质呼吸剂，以确定是否存在相关性 这是这些生物标志物的水平和疾病进展的速度。特别是我们将衡量 磷酸化的重神经丝与补体3（31）的比例，以查看此比率是否为 预测疾病进展以及美容治疗期间的水平是否变化 ' 这个项目对这种不可治疗的疾病具有独特的见解。 LF这项研究证实 早期的结果并表明，当与riluzole结合使用时，纪念碑明显 减慢了疾病的进展，并减轻患者的认知缺陷 使用额 - 脑辅助功能，它将为进行较大的LLL试验奠定基础。