Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD

September 8, 2020 updated by: L. Eugene Arnold, Ohio State University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
144

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Asheville, North Carolina, United States, 28804
        • University of North Carolina at Asheville
    • Ohio
      • Columbus, Ohio, United States, 43215
        • The Ohio State University Nisonger Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

7 years to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Neurofeedback treatment
The intended treatment is downtraining of theta power and uptraining of beta power for 38 treatments of active NF.
Device: Neurofeedback treatment

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:

  1. The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)
  2. Average voltage of theta waves
  3. Average voltage of beta
  4. Average ratio of theta to beta power (TBR)
Placebo Comparator: Sham neurofeedback treatment
Participants assigned to sham and their trainers will be fed EEG data from pre-recorded files (recorded during live clinical NF) rather than from the participant's live signal. In order to prevent unblinding of experienced NF trainers/technicians, artifacts from the participant's EMG and EOG are blended into the pre-recorded EEG so that the trainer controlling the feedback cannot differentiate between live and simulated data. To insure trainer/technician blindness, the pre-recorded EEG will be 38 consecutive EEGs from the same age-matched clinical case so that EEGs of the sham group will also show "training progress" over successive sessions, like real NF.
Device: Neurofeedback treatment

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:

  1. The number of half-second periods that they met the reward parameters (i.e. theta mV below threshold; beta mV above threshold)
  2. Average voltage of theta waves
  3. Average voltage of beta
  4. Average ratio of theta to beta power (TBR)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Scores of Teacher and Parent Rated Inattentive Symptoms
Time Frame: Assessed at Baseline, Mid-treatment (2 months), End-treatment (4 months), at 6 month follow up, at 13 month follow up
The primary outcome measure is the composite scores of teacher and parent-rated inattentive symptoms on the Conners-3, rated on a scale of 0-3. Lower scores represent a better outcome, with a maximum score of 3 and a minimum score of 0.
Assessed at Baseline, Mid-treatment (2 months), End-treatment (4 months), at 6 month follow up, at 13 month follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ohio State University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)
University of North Carolina

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: L. Eugene Arnold, MD, MEd, The Ohio State University Nisonger Center
  • Principal Investigator: Roger deBeus, Ph.D., University of North Carolina at Asheville

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 29, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 29, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 8, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2013H0417
  • 1R01MH100144-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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