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 接受脑瘤放射治疗的儿童有显著的认知影响风险 负面影响的疾病和治疗(例如注意力、记忆力和处理速度的问题) 生活质量，包括学业和社会成就下降。低级别胶质瘤占30%至50% 儿童脑瘤，存活率高，无进展存活率约80%。 长期随访。随着幸存者人数的增加，改善长期认知结果的努力 变得势在必行。这项研究计划的一个主要目标是开发干预措施，以减轻 中枢神经系统定向治疗对儿童癌症幸存者生活质量的影响。血管假说 提示辐射损伤的机制类似于小血管疾病，如 血管性痴呆症，促使人们对治疗血管性痴呆症感兴趣。随机安慰剂- 对照试验显示美金刚(一种阻断神经递质的NMDA受体的药物 谷氨酸)改善轻至中度血管性痴呆患者的认知功能，而不涉及副作用 效果。此外，美金刚在放射治疗成人脑转移瘤期间的疗效已被证明是良好的。 与安慰剂相比，随着时间的推移，患者的认知能力下降较少。对注意力缺陷儿童的研究 多动障碍或自闭症谱系障碍表明美金刚是安全的，有证据表明 提高了认知能力。重要的是，目前还没有关于美金刚治疗儿童的公开研究。 治疗脑瘤。决定我们是否能保持认知能力已成为至关重要的问题 通过预防性干预治疗癌症的儿童在出现远期效应之前的功能。 因此，本研究的具体目的是：1)估计参与率、服药依从性 美金刚作为儿童神经保护剂的研究中认知评估的完成 对低级别胶质瘤进行放射治疗；2)评估神经行为改变的程度 与美金刚相关的结果(认知、社交、生活质量、神经学)；以及3)评估 美金刚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、安慰剂对照设计，6至21岁儿童计划 接受低度恶性胶质瘤的头颅放射治疗。参与者将随机接受任何一种美金刚治疗 (20毫克/天)或与之匹配的安慰剂。在12周的药物治疗阶段，参与者将收到每周的电话 呼吁评估服药依从性和副作用。基线、6周(放射治疗结束)和12周 几周(美金刚用药阶段结束)将使用以下方法进行额外的副作用监测 实验室检查、体检和完成心电检查。在相同的三个时间点，和一个 一年后，参与者将完成认知功能的实验室测量，并参与神经学 考试。我们将招募参与者，直到30人完成12周评估时间点。