Neurostimulation in Adult Survivors of Childhood Leukemia

儿童白血病成年幸存者的神经刺激

• 批准号: 10153718
• 负责人: Tara M Brinkman
• 金额: $ 62.35万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153718
• 关键词: Acute Lymphocytic Leukemia; Adult; Age; Anisotropy; Anxiety; Brain; Brain imaging; Brain region; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Clinical Trials; Cranial Irradiation; Cytarabine; Data; Development; Diffuse; Diffusion Magnetic Resonance Imaging; Dose; Employment; Executive Dysfunction; Fatigue; Functional Magnetic Resonance Imaging; Home; Intervention; Intravenous; Long-Term Survivors; Measures; Methotrexate; Morbidity - disease rate; Myelin; Neurocognitive; Neurocognitive Deficit; Outcome; Pain; Patient Self-Report; Patients; Pattern; Placebos; Prefrontal Cortex; Psychological adjustment; Randomized; Reporting; Risk; Safety; Sampling; Serum; Short-Term Memory; Social Functioning; Structure; Survivors; Symptoms; Testing; Work; base; cancer therapy; childhood cancer survivor; cognitive training; common symptom; depressive symptoms; dissemination strategy; efficacious intervention; efficacy evaluation; emotion regulation; emotional functioning; environmental adaptation; executive function; implementation strategy; improved; neural network; neuroimaging; optimal treatments; pilot trial; randomized placebo controlled study; remediation; remote delivery; skills; standard of care; therapy design; treatment center; white matter

ABSTRACT Adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation, intrathecal methotrexate (MTX), or high dose intravenous MTX and/or cytarabine are at risk for neurocognitive morbidities, particularly in the domain of executive function. Deficits in executive function have been associated with reduced educational attainment, employment, emotional functioning, and social functioning in survivors. We have recently identified that higher treatment intensity, as reflected through serum concentration of MTX, is associated with worse executive functioning, increased brain activation in dorsolateral prefrontal regions based on functional MRI, and decreased myelin integrity in frontostrial tracts based on diffusion tensor imaging. This suggests that frontal brain regions may be less efficient in survivors treated with more intense therapies than those treated with less intensive therapy. Therefore, interventions designed to target the dorsolateral region and focus on remediation of executive functioning skills may be particularly beneficial for survivors. Importantly, because most long-term survivors do not reside in close proximity to their primary cancer treatment center, the need for interventions that can be delivered remotely is critical. We recently piloted a two-month trial of remote transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex paired with cognitive training for the treatment of executive dysfunction in a randomly selected sample of 30 adult survivors of childhood ALL (mean age 33 years, SD 7.5 years). Among the 27 survivors eligible for remote stimulation, 25 (93%) completed at least 50% of the home-based sessions, and 22 (81%) completed all prescribed sessions. These data support the safety, acceptability, and feasibility of remote tDCS among long-term survivors. Among the survivors who completed the intervention, we observed significant improvements on a direct measure of executive functioning (working memory: 0.5 SD increase) and self-reported emotional regulation (0.7 SD increase). Now, we propose a randomized placebo-controlled study to examine the efficacy of home-based tDCS + remote cognitive training vs. sham (placebo) + remote cognitive training on symptoms of executive dysfunction in a larger sample of long-term survivors of ALL. We also will examine impact of tDCS and cognitive training on underlying neural networks via brain imaging. Results of this study will lead to the development of subsequent clinical trials to examine optimal treatment intensity and duration as well as dissemination and implementation strategies. This work has the potential to significantly impact current standard of care with a scalable intervention for common symptoms of executive dysfunction in long-term survivors of childhood cancer.

抽象的 儿童期急性淋巴细胞白血病（全部）接受颅辐射治疗的儿童急性淋巴细胞白血病（全部） 甲氨蝶呤（MTX）或高剂量的静脉内MTX和/或细胞ara虫有神经认知性病的风险， 特别是在执行功能领域。执行功能的缺陷与减少有关 幸存者中的教育成就，就业，情感功能和社会功能。我们最近有 确定通过MTX的血清浓度反映的更高的治疗强度与 执行功能较差，基于功能的背外侧前额叶区域的大脑激活增加 MRI，并根据扩散张量成像降低了额膜片的髓磷脂完整性。这表明这一点 与接受治疗的幸存者相比 不太强化的疗法。因此，旨在针对背外侧区域的干预措施并关注 对执行功能的补救措施可能对幸存者特别有益。重要的是，因为大多数 长期幸存者不属于其主要癌症治疗中心的近距离 可以远程提供的干预措施至关重要。我们最近试行了为期两个月的远程经颅试验 直接电流刺激（TDC）到背侧前额叶皮层，并与认知训练配对 在30个童年成年幸存者的随机样本中治疗执行功能障碍 年龄33岁，SD 7.5岁）。在符合远程刺激的27个幸存者中，至少有25个（93％）完成 50％的家庭会议和22％（81％）完成了所有规定的会议。这些数据支持 长期幸存者中远程TDC的安全性，可接受性和可行性。在幸存者中 完成了干预措施，我们观察到了直接衡量执行功能的重大改进 （工作记忆：增加0.5 SD）和自我报告的情绪调节（增加0.7 SD）。现在，我们建议 一项随机安慰剂对照研究，以检查基于家庭的TDC +远程认知的功效 培训与假（安慰剂） +较大样本中执行功能障碍症状的远程认知培训 所有人的长期幸存者。我们还将检查TDC和认知培训对潜在神经的影响 通过大脑成像网络。这项研究的结果将导致随后的临床试验发展 检查最佳治疗强度和持续时间以及传播和实施策略。这 工作有可能对当前的护理标准进行重大影响，并进行可扩展的干预措施 在儿童癌症长期幸存者中执行功能障碍的症状。