Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Low Grade Glioma

美金刚用于预防接受低级别胶质瘤颅脑放射治疗的儿科患者的认知迟发效应

• 批准号: 9372822
• 负责人: HEATHER M CONKLIN
• 金额: $ 15.62万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9372822
• 关键词: 21 year old; Address; Adult; Adverse effects; Attention; Attention deficit hyperactivity disorder; Blood Vessels; Brain Neoplasms; Cerebral Ischemia; Child; Childhood Brain Neoplasm; Clinical; Cognition; Cognitive; Cognitive deficits; Cranial Irradiation; Disease; Double-Blind Method; Electrocardiogram; Enrollment; Event; Failure; Frequencies; Glioma; Glutamates; Goals; Hypoxic-Ischemic Brain Injury; Impaired cognition; Impairment; Injury; Intervention; Interview; Laboratories; Late Effects; Literature; Longitudinal Studies; Malignant Neoplasms; Measures; Mediating; Memantine; Metastatic malignant neoplasm to brain; Microvascular Dysfunction; Monitor; Morbidity - disease rate; N-Methyl-D-Aspartate Receptors; NMDA receptor antagonist; Nature; Neurologic; Neurons; Neuroprotective Agents; Neurotransmitter Receptor; Outcome; Outcome Measure; Participant; Patients; Pharmaceutical Preparations; Phase; Phonation; Physical Examination; Placebo Control; Placebos; Population; Prevention; Progression-Free Survivals; Publishing; Quality of life; Radiation; Radiation Injuries; Radiation therapy; Randomized; Recruitment Activity; Research; Risk; Schedule; Secondary to; Survival Rate; Survivors; Telephone; Time; Unemployment; Vascular Dementia; autism spectrum disorder; base; chemotherapy; childhood cancer survivor; cognitive function; cognitive testing; design; follow-up; improved; interest; irradiation; medication compliance; memory process; neurobehavioral; neurotoxicity; pediatric patients; pill; pilot trial; processing speed; programs; prophylactic; radiation-induced injury; randomized placebo controlled trial; social; therapy development

PROJECT SUMMARY/ABSTRACT Children who receive radiation therapy for brain tumors are at significant risk for cognitive effects of their disease and treatment (e.g., problems with attention, memory and processing speed) that negatively impact quality of life, including reduced academic and social attainment. Low grade gliomas account for 30 to 50% of childhood brain tumors and have high survival rates, with progression-free survival rates approximately 80% on long-term follow-up. With a growing survivor population, efforts to improve long-term cognitive outcomes become imperative. A primary goal of this research program is development of interventions that mitigate the impact of CNS-directed therapies on the quality of life of childhood cancer survivors. The vascular hypothesis of radiation injury suggests that the mechanism of radiation-induced injury is similar to small vessel disease as seen with vascular dementia, prompting interest in treatments for vascular dementia. Randomized placebo- controlled trials have shown memantine (a drug that blocks NMDA receptors for the neurotransmitter glutamate) improves cognition in patients with mild to moderate vascular dementia without concerning side effects. Further, memantine during radiotherapy for brain metastases in adults has been shown to be well tolerated with less cognitive declines over time relative to placebo. Studies with children with Attention Deficit Hyperactivity Disorder or autism spectrum disorders have shown memantine is safe with evidence for improved cognition. Importantly, there are no published studies of memantine in children undergoing treatment for brain tumors. It has become of paramount importance to determine whether we can preserve cognitive function of children treated for cancer by intervening prophylactically, before the emergence of late effects. Accordingly, the specific aims of this study are: 1) To estimate the rate of participation, medication adherence and completion of cognitive assessments in a study of memantine used as a neuroprotective agent in children undergoing radiotherapy for low grade glioma; 2) To estimate the magnitude of change in neurobehavioral outcomes (cognitive, social, quality of life, neurologic) associated with memantine; and 3) To evaluate the frequency and nature of memantine side effects. In order to investigate these aims, we propose to use a randomized, double-blind, placebo-controlled design with children between 6 and 21 years of age scheduled to undergo cranial radiation therapy for a low grade glioma. Participants will be randomized to either memantine (20 mg/d) or a matching placebo. During the 12 week medication phase, participants will receive weekly phone calls to assess medication adherence and side effects. At baseline, 6 weeks (end of radiation therapy) and 12 weeks (end of the memantine medication phase) additional side effect monitoring will take place using laboratory values, physical examination and completion of an ECG. At the same three time points, and one year later, participants will complete laboratory measures of cognitive function and participate in neurologic exams. We will recruit participants until 30 have completed the 12 week assessment time point.

项目摘要/摘要 接受脑肿瘤放射疗法的儿童对其认知作用有很大的风险 疾病和治疗（例如，注意力，记忆和处理速度问题）对 生活质量，包括降低学术和社会成就。低级神经胶质瘤占30％至50％的占 儿童脑肿瘤且生存率高，无进展生存率约为80％ 长期随访。随着幸存者人数的增长，改善长期认知结果的努力 成为当务之急。该研究计划的主要目标是开发干预措施，以减轻 CNS指导疗法对儿童癌症幸存者生活质量的影响。血管假设 辐射损伤表明，辐射诱导的损伤机制类似于小血管疾病 患有血管性痴呆，引起人们对血管痴呆疗法的兴趣。随机安慰剂 - 对照试验显示了美容（一种阻断神经递质NMDA受体的药物 谷氨酸）改善轻度至中度血管性痴呆患者的认知，而无需一侧 效果。此外，在放射治疗期间的美容疗法对成人的脑转移量已被证明很好 相对于安慰剂，随着时间的推移，认知能力下降的耐受性较小。与儿童注意力不足的研究 多动症障碍或自闭症谱系障碍表明美金刚症是安全的，有证据表明 改善认知。重要的是，在接受治疗的儿童中没有关于美灵的发表研究 用于脑肿瘤。确定我们是否可以保持认知能力是至关重要的 在晚期作用出现之前，通过预防性干预治疗癌症的儿童的功能。 因此，本研究的具体目的是：1）估计参与率，药物依从性 在一项用作儿童神经保护剂的纪念剂研究中，认知评估的完成 接受放疗低级神经胶质瘤； 2）估计神经行为变化的幅度 与美容有关的结果（认知，社会，生活质量，神经系统质量）； 3）评估 美容副作用的频率和性质。为了调查这些目标，我们建议使用 随机，双盲，安慰剂控制的设计，有6至21岁的儿童计划 接受颅辐射疗法的低级神经胶质瘤。参与者将被随机分配到任何美容 （20 mg/d）或匹配的安慰剂。在12周的药物阶段，参与者将每周接收电话 呼吁评估药物依从性和副作用。基线，6周（放射治疗结束）和12 几周（美容药物阶段结束）将使用其他副作用监测 实验室价值，体格检查和ECG的完成。在相同的三个时间点，一个 一年后，参与者将完成认知功能的实验室措施并参与神经系统 考试。我们将招募参与者，直到30岁完成了12周的评估时间点。