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: 8880284
• 负责人: L EUGENE ARNOLD
• 金额: $ 61.95万
• 依托单位: OHIO STATE UNIVERSITY
• 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 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8880284
• 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; Eye; FDA approved; Funding; Health; Impairment; Individual; Internet; Left; 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; Structure; Subgroup; 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; primary outcome; programs; 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）：目前建立的注意力缺陷/多动障碍（ADHD）循证治疗方法不完全有效，也不被普遍接受，尽管有显著的直接益处，但随着时间的推移，效果似乎会减弱，例如，FDA批准的药物显示出很大的急性益处，即使与行为治疗相结合，也只有三分之一的儿童得到部分治疗，并且在2年后没有被证明有效。需要额外的治疗，这些治疗是有效的，具有持续的益处，优选地与预测治疗反应的生物标志物相关。一个很好的候选者是脑电图（EEG）生物反馈，称为神经反馈（NF）。其基于1）ADHD患者通常具有过多的θ频带（4- 8Hz）定量EEG功率、低β频带（13-21 Hz）功率和过多的θ-β比率（TBR）的观察，以及2）操作性条件反射的理论应用以校正这种EEG不平衡。对6项随机临床试验的Meta分析发现，对注意力不集中症状有较大获益，对多动-冲动症状有中等获益。不幸的是，这些都不是盲目的。4项小型盲法研究中有3项发现NF与假手术相比没有优势，但使用了次优NF，导致情况不确定。由于NF所需的费用和时间，有一个公共卫生需要确定它是否有一个具体的效果，除了明显的非特异性的好处，做一个集中的活动，每周几次与一个友好的，鼓励成年人谁加强参加任务。神经纤维症，多动症，临床试验，统计学，广告数据管理已加入设计一个双盲假对照随机临床试验，以回答几个紧迫的科学和临床问题的方式，将是可信的所有。（1所大学和1所NF诊所）70名儿童（总N=140）年龄7至10岁的患有严格诊断的中度至重度ADHD和TBR>5的儿童将被随机分配到3：2与NF的主动TBR减量训练的比率与相同持续时间、强度和外观的假训练的比率。为了使参与者和研究人员保持盲态，假手术将使用预先记录的EEG，其中叠加了参与者的伪影。假手术将由一名与参与者没有联系的非现场统计学家指导人员通过互联网编程到设备中。治疗保真度将由2名公认的NF负责人以保护盲态的方式进行培训和监测。在基线、治疗中期、治疗结束和6个月、1年和2年随访时的多领域评估将包括父母和教师对症状和损伤的评级、神经心理学测试、临床医生评级和定量EEG以及盲法和假惰性测试。假设包括NF将改善父母和教师评定的注意力不集中症状（主要结局）和其他结局，超过假手术，培训后获益将持续2年，初始TBR将缓和治疗反应，TBR的变化将介导反应。研究领域标准和脑电图大脑的变化将进行探讨，包括TBR的临床症状，执行功能障碍和睡眠的关系。