Double-Blind Randomized Clinical Trial of EEG Neurofeedback for ADHD

脑电图神经反馈治疗多动症的双盲随机临床试验

• 批准号: 9411382
• 负责人: L EUGENE ARNOLD
• 金额: $ 16.48万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9411382
• 关键词: 10 year old; Acute; Adult; Affect; Age; Appearance; Arousal; Attention deficit hyperactivity disorder; Behavior Therapy; Biofeedback; Biological Markers; Blinded; Brain; Brain imaging; Budgets; Child; Clinic; Clinical; Clinical Trials; Diagnosis; Dose; Double-Blind Method; Electromagnetics; Equipment; Event-Related Potentials; Evidence based treatment; Executive Dysfunction; Eye; FDA approved; Funding; Hyperactive behavior; Impairment; Impulsivity; Individual; Internet; Italy; Literature; Measures; Mediating; Mediator of activation protein; Meta-Analysis; Monitor; Morphologic artifacts; National Institute of Mental Health; Neuropsychological Tests; Only Child; Operant Conditioning; Outcome; Parents; Participant; Patient observation; Persons; Pharmaceutical Preparations; Placebo Control; Placebo Effect; Placebos; Public Health; Public Policy; Publishing; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Regulation; Research Domain Criteria; Resolution; Sampling; Severities; Site; Sleep; Standardization; Structure; Symptoms; Testing; Therapeutic Effect; Time; Training; Treatment Cost; Universities; base; blind; clinical practice; cost; data management; design; disorder subtype; evidence base; executive function; follow-up; impression; improved; inattention; neurofeedback; predictive marker; predictive of treatment response; primary outcome; public health relevance; response; screening; statistics; teacher; tomography; treatment effect; treatment response; trend

DESCRIPTION (provided by applicant): Current established evidence-based treatments for attention-deficit/hyperactivity disorder (ADHD) are incompletely effective and not universally acceptable, and appear to wane in effect over time despite significant immediate benefit e.g., FDA-approved medication, which shows large acute benefit, leaves a third of children only partially treated even when combined with behavioral treatment, and has not been demonstrated effective beyond 2 years. Additional treatments are needed that are effective with persisting benefit, preferably related to a biomarker predicting treatment response. A good candidate is electroencephalographic (EEG) biofeedback, called neurofeedback (NF). It is based on 1) observations that patients with ADHD often have excessive theta band (4-8 Hz) quantitative EEG power, low beta band (13-21 Hz) power, and excessive theta- beta ratio (TBR), and 2) theoretical application of operant conditioning to correct this EEG imbalance. Meta- analysis of 6 randomized clinical trials found a large benefit for inattentive symptoms and medium benefit for hyperactive-impulsive symptoms. Unfortunately, none of these were blinded. Three of 4 small blinded studies found no advantage for NF over sham, but used suboptimal NF, leaving the situation inconclusive. Because of the expense and time required by NF, there is a public health need to determine whether it has a specific effect beyond the obvious nonspecific benefit of doing a focused activity several times a week with a friendly, encouraging adult who reinforces for attending to the task. Experts in NF, ADHD, clinical trials, statistics, ad data management have joined to design a double-blind sham-controlled randomized clinical trial to answer several pressing scientific and clinical questions in a way that will be credible to all.At each of 2 sites (1 university & 1 NF clinic) 70 children (total N=140) age 7 through 10 with rigorously diagnosed moderate to severe ADHD and TBR>5 will be randomized in a 3:2 ratio to active TBR downtraining by NF vs. a sham training of equal duration, intensity, and appearance. To keep both participants and study staff blind, the sham will utilize pre-recorded EEGs with the participant's artifacts superimposed. The sham will be programmed into the equipment via internet by an off-site statistician-guided person who has no contact with participants. Treatment fidelity will be trained and monitored by 2 acknowledged NF leaders in a manner that protects blinding. Multi-domain assessments at baseline, mid-treatment, treatment end, and follow-ups at 6 months, 1 year, and 2 years will include parent and teacher ratings of symptoms & impairment, neuropsychological tests, clinician ratings, and quantitative EEG as well as tests of blinding and of sham inertness. Hypotheses include that NF will improve parent- and teacher-rated inattentive symptoms (primary outcome) and other outcomes more than sham, that benefit will persist for 2 years after training, that initial TBR will moderate treatment response, and tha change in TBR will mediate response. Research Domain Criteria and EEG brain changes will be explored, including relationship of TBR to clinical symptoms, executive-function impairment, and sleep.

描述（由申请人提供）：目前建立的针对注意力缺陷/多动障碍（ADHD）的循证治疗方法并不完全有效，并且不是普遍接受的，并且随着时间的推移，尽管有显着的直接益处，但效果似乎会减弱，例如，fda批准的药物，显示出巨大的急性益处，即使与行为治疗相结合，也有三分之一的儿童仅得到部分治疗，并且未被证明有效超过2年。需要其他有效且持续获益的治疗，最好与预测治疗反应的生物标志物相关。脑电图（EEG）生物反馈是一个很好的选择，也被称为神经反馈（NF）。基于1)观察到ADHD患者常存在theta波段（4- 8hz）定量脑电图功率过高、beta波段（13- 21hz）功率过低、theta- beta比（TBR）过高的现象，以及2)操作性条件反射的理论应用来纠正这种脑电图失衡。6个随机临床试验的荟萃分析发现，对注意力不集中症状有很大的益处，对多动冲动症状有中等的益处。不幸的是，这些实验都不是盲法的。4个小的盲法研究中有3个没有发现NF优于假手术，但使用了次优的NF，使得情况不确定。由于NF所需的费用和时间，公共卫生需要确定它是否具有特定的效果，而不是与一个友好的、鼓励的成年人每周做几次集中的活动所带来的明显的非特定好处。NF、ADHD、临床试验、统计学和数据管理方面的专家联合设计了一项双盲、假对照的随机临床试验，以一种对所有人都可信的方式回答几个紧迫的科学和临床问题。在2个地点（1所大学和1所NF诊所），70名7至10岁的儿童（总N=140）被严格诊断为中度至重度ADHD和TBR bb0 5，将按3:2的比例随机分为NF主动TBR下降训练和相同持续时间、强度和外观的假训练。为了让参与者和研究人员都看不见，假实验将使用预先记录的脑电图，并叠加参与者的人工制品。假手术将由一名与参与者没有任何联系的非现场统计员指导的人员通过互联网编程到设备中。治疗保真度将由两名公认的NF领导者以保护盲法的方式进行培训和监测。基线、治疗中期、治疗结束时的多领域评估以及6个月、1年和2年的随访将包括家长和老师对症状和损伤的评分、神经心理测试、临床医生评分、定量脑电图以及盲法和假惰性测试。假设包括：NF比假训练更能改善家长和老师评定的注意力不集中症状（主要结果）和其他结果，训练后的效果将持续2年，初始TBR将缓和治疗反应，TBR的改变将调节反应。研究领域标准和脑电图脑变化将探讨，包括TBR与临床症状，执行功能障碍和睡眠的关系。