Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 7 - 10 |
| Updated: | 3/17/2019 |
| Start Date: | September 2014 |
| End Date: | April 2020 |
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.
(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.
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.
(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.
Inclusion Criteria:
- Boys and girls age 7 to 10
- IQ>80
- diagnosed DSM-5 ADHD inattentive presentation or combined presentation
- an item mean ≥1.5 sd above norms on a 0-3 metric both on parent ratings of either
DSM-IV inattentive symptoms or all 18 ADHD symptoms and on teacher ratings of either
inattentive symptoms or all 18 ADHD symptoms
- an eyes-open QEEG with theta-beta power ratio >4.5 at Cz or Fz
Exclusion Criteria:
- comorbid disorder requiring psychoactive medication other than FDA-approved ADHD
medication
- a medical disorder requiring systemic chronic medication with confounding psychoactive
effects
- sleep apnea
- restless legs syndrome
- IQ <80
- plans to move requiring school change during the next 3 months
- plans to start other ADHD treatment in the next 3 months
- antipsychotic agent in the 6 months prior to baseline assessment
- fluoxetine in the 4 weeks prior to baseline
- other psychiatric medication in the two weeks prior to baseline
->5 previous NF treatments
- Vitamin D deficiency will be a temporary exclusion
We found this trial at
2
sites
Columbus, Ohio 43210
Principal Investigator: L Eugene Arnold, M.D., M.Ed.
Phone: 614-685-6708
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Asheville, North Carolina 28804
Principal Investigator: Roger deBeus, Ph.D.
Phone: 828-333-5359
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