Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD
Condition: Attention-Deficit/Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Interventional

Summary: 
      Additional treatments with long-term benefit for attention-deficit/hyperactivity disorder
      (ADHD) are needed; one of the more promising is neurofeedback (EEG biofeedback), which has
      several randomized controlled trials showing significant benefit, but which are inconclusive
      because they were not double-blinded; the benefit could have been nonspecific (placebo
      response). Because of neurofeedback's labor-intensive cost (1 treatment costing as much as a
      month's medication), It is important to know how much specific benefit it yields. This 2-
      site placebo-controlled double-blind randomized clinical trial is the first to test for a
      specific benefit of neurofeedback with adequate power, the first designed and implemented
      collaboratively by experts in neurofeedback, ADHD, and clinical trials, the first to
      rigorously monitor quality not only of treatment, but also of placebo and blinding, and the
      first to follow up for 2 years to examine enduring effect; the results, whether positive or
      negative, will provide evidence for clinical practice and public policy regarding ADHD.
    

Detailed description: 
      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. Metaanalysis
      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, and 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
      that 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.
    

Intervention name(s): Neurofeedback treatment
Intervention type(s): Device
Intervention description(s): Each session, the child participates in 5 training tasks. Each task lasts 5 minutes at the beginning and gradually increases to 9 minutes per task over the course of the neurofeedback as the child's attention span improves. We record four results for each of the 5 tasks:
The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)
Average voltage of theta waves
Average voltage of beta
Average ratio of theta to beta power (TBR)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ADHD; Attention-Deficit/Hyperactivity Disorder; neurofeedback; EEG