Developmental Pilot Study of External Trigeminal Nerve Stimulation for ADHD

三叉神经外刺激治疗多动症的初步研究

• 批准号: 8776636
• 负责人: Sandra K Loo
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8776636
• 关键词: Action Potentials; Acute; Address; Adult; Adverse effects; Adverse event; Affect; Aftercare; Anterior; Anxiety; Area; Attention; Attention deficit hyperactivity disorder; Behavior; Behavior Disorders; Behavioral; Blinded; Brain; Brain Diseases; Cardiovascular system; Categories; Child; Childhood; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Development; Diagnostic; Dimensions; Disease; Double-Blind Method; Electric Stimulation; Electrodes; Electroencephalography; Emotional disorder; Emotions; Epilepsy; Equipment and supply inventories; Event-Related Potentials; Exhibits; Forehead; Foundations; Frequencies; Grant; Habits; Health Care Costs; Height; Intervention; Intervention Studies; Laboratories; Link; Manifest Anxiety Scale; Measures; Mental Depression; Mental disorders; Methods; Mission; Moods; National Institute of Mental Health; Outcome; Parents; Participant; Pharmaceutical Preparations; Pilot Projects; Positron-Emission Tomography; Preparation; Process; Psychopathology; Questionnaires; Randomized; Randomized Controlled Trials; Reaction Time; Refractory; Research; Research Domain Criteria; Research Personnel; Resistance; School-Age Population; Short-Term Memory; Sleep; Source; Symptoms; TNFRSF5 gene; Testing; Time; Treatment outcome; Trigeminal nerve structure; United States; Weight; Work; Youth; base; child depression; cingulate cortex; clinical efficacy; efficacy trial; executive function; follow-up; functional disability; improved; innovation; psychosocial; psychostimulant; public health relevance; randomized trial; response; success; teacher; therapy design; treatment effect

DESCRIPTION (provided by applicant): Attention-Deficit/Hyperactivity Disorder (ADHD) is estimated to affect up to 9.5% of school-aged children and 4.4% of adults. ADHD is associated with increased functional impairments, comorbid psychopathology, and overall health care costs. Although various psychosocial interventions are employed, medication remains the mainstay of ADHD treatment. It is estimated that over 2.8 million children in the United States are prescribed psychostimulants, mostly for ADHD. Although these are generally safe and effective in acute treatment, considerable concerns remain about side effects and the absence of demonstrated long-term benefit. Parents are highly ambivalent about using ADHD medications. While there is great demand for non- medication approaches to ADHD, most popular alternatives are not linked to any mechanistic understanding of brain processes and similarly lack significant scientific evidence to support their use. External trigeminal nerve stimulation (eTNS) is a non-invasive method of brain modulation with demonstrated success in treating adults with medication-resistant epilepsy and depression. In eTNS, the trigeminal nerve receives low current electrical stimulation via an electrode applied to the forehead and worn during sleep. Preliminary adult studies revealed significant improvements in mood, sleep, and attention. PET imaging demonstrated acute eTNS-related activation in brain areas involved in attention and executive functioning. A preliminary pediatric study based on this work assessed the feasibility of eTNS for ADHD. Results demonstrated that eTNS was well tolerated and accepted, and was associated with significant improvements in ADHD symptoms and laboratory measures of response inhibition and working memory. This R34 proposes a three-year clinical trial development project to further standardize eTNS in preparation for definitive ADHD efficacy trials and to elucidate underlying brain mechanisms that will potentially support use of eTNS in ADHD as well as other behavioral, emotional, and cognitive disorders. The project is a four-week double-blind randomized trial of active vs. sham eTNS followed by four weeks follow-up after treatment discontinuation. Participants will have repeated assessments on behavioral ratings, cognitive processes, and cortical activation via electroencephalography (EEG). This study will assess differences in outcome trajectories by condition in the first randomized controlled trial of eTNS for ADHD, validity and fidelity of sham eTNS as a blinded control, time course effects regarding onset and offset of response, and underlying mechanisms of brain change that are associated with treatment outcomes. The proposal is consistent with several NIMH priorities, including the development of innovative interventions and designs for intervention studies, development of an integrated understanding of brain disorder processes that provide the foundation for understanding mental disorders, and assessment of the mechanisms of action of efficacious interventions in the brain.

描述（由申请人提供）：据估计，注意力缺陷/多动症 (ADHD) 影响高达 9.5% 的学龄儿童和 4.4% 的成人。 ADHD 与功能障碍、共病精神病理学和总体医疗保健费用增加有关。尽管采用了各种心理社会干预措施，但药物仍然是多动症治疗的支柱。据估计，美国有超过 280 万儿童服用精神兴奋剂，主要用于治疗多动症。尽管这些药物在急性治疗中通常是安全有效的，但人们仍然对副作用和缺乏已证明的长期益处存在相当大的担忧。父母对于使用多动症药物非常矛盾。虽然对治疗多动症的非药物方法有很大的需求，但大多数流行的替代方法与对大脑过程的任何机械理解无关，并且同样缺乏重要的科学证据来支持其使用。外部三叉神经刺激（eTNS）是一种非侵入性的大脑调节方法，在治疗成人耐药性癫痫和抑郁症方面已被证明是成功的。在 eTNS 中，三叉神经通过贴在前额并在睡眠期间佩戴的电极接受低电流电刺激。初步成人研究显示情绪、睡眠和注意力显着改善。 PET 成像显示，与注意力和执行功能有关的大脑区域存在与 eTNS 相关的急性激活。基于这项工作的一项初步儿科研究评估了 eTNS 治疗 ADHD 的可行性。结果表明，eTNS 具有良好的耐受性和接受性，并且与 ADHD 症状以及反应抑制和工作记忆的实验室测量的显着改善相关。 R34 提出了一个为期三年的临床试验开发项目，以进一步标准化 eTNS，为明确的 ADHD 疗效试验做好准备，并阐明潜在的大脑机制，这些机制将有可能支持 eTNS 在 ADHD 以及其他行为、情绪和认知障碍中的使用。该项目是一项为期 4 周的双盲随机试验，对主动 eTNS 与假 eTNS 进行比较，然后在停止治疗后进行 4 周的随访。参与者将通过脑电图（EEG）对行为评级、认知过程和皮质激活进行重复评估。这项研究将评估第一个 eTNS 治疗 ADHD 随机对照试验中不同条件下结果轨迹的差异、假 eTNS 作为盲法对照的有效性和保真度、反应开始和抵消的时间过程影响，以及大脑变化的潜在机制。与治疗结果相关。该提案与 NIMH 的几个优先事项一致，包括开发创新干预措施和干预研究设计、发展对脑部疾病过程的综合理解，为理解精神障碍奠定基础，以及评估有效干预措施的作用机制。大脑。