Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Neurofeedback
Brief summary
Neurofeedback is increasingly advocated for treatment of ADHD despite a thin evidence base. The numerous open and partially controlled studies suffer serious design flaws. In particular, there is no published double-blind randomized clinical trial (RCT), which would control for experimenter and participant biases. The primary aim of this R34 pilot study is to conduct a small-scale pilot with 39 8-12 year-olds with ADHD to prepare for such a larger RCT.
Detailed description
Thirty-nine boys and girls aged 6-12 with rigorously diagnosed DSM-IV ADHD not currently taking medication will be twice-randomized: first to active neurofeedback (n=26) vs. sham neurofeedback (n=13), and simultaneously to 2 vs. 3 times a week treatment frequency (at least 18 in each frequency, 12 active and 6 sham) for 40 treatments. At treatment 24, major assessments will include measures of satisfaction and blinding, and subjects will be given the option of switching to the opposite treatment frequency for the remaining 16 treatments to generate a practical measure of schedule palatability. Major assessments (at baseline, treatment 12, treatment 24, treatment 40, and follow-up) will include measures of symptoms, functional impairment, academic performance/achievement, and neuropsychological tests of attention, vigilance, and executive functioning. Every 3 treatments parents will rate ADHD symptoms and every 6 treatments teachers will rate, to track the response curve over time. Baseline EEG arousal and ADHD subtype will be examined as possible moderators. By determining the optimal frequency and number of treatments and demonstrating feasibility of double blinding, this pilot study should pave the way for a definitive large RCT of neurofeedback.
Interventions
DEVICEActive Neurofeedback
A comparison of active neurofeedback to sham neurofeedback and of two treatment schedules: twice weekly vs. three times a week, with the same amount of total treatment over 40 sessions, varying only in frequency.
DEVICESham neurofeedback
Active neurofeedback vs. sham neurofeedback for 40 treatments, either twice or three times per week.
Sponsors
National Institute of Mental Health (NIMH)
Brain Resource Center
L. Eugene Arnold
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Age 6-12 inclusive. * Boys and girls. * Primary diagnosis of ADHD, inattentive or combined type. * Not currently taking medication for ADHD. * Primary caretaker who can provide frequent parent ratings. * Item mean ≥1.5 on a 0-3 metric on parent/teacher ratings of DSM-IV inattentive symptoms or on parent/teacher ratings of all 18 ADHD symptoms (while off medication). * IQ 80 or above and mental age of 6 years or more. * Willingness and ability to come for 40 treatment sessions and to cooperate with assessments. * Informed consent and assent
Exclusion criteria
* Comorbid disorder requiring psychoactive medication including psychosis, bipolar disorder, severe major depression, and severe anxiety disorders. Patients with mild depression or anxiety not requiring pharmacotherapy will be included and the comorbid symptoms will be tracked.Pervasive developmental disorder is exclusionary by DSM-IV definition of ADHD. * Medical disorder requiring systemic chronic medication that has confounding psychoactive effects. Asthma inhalants will be allowed, but not chronic systemic corticoids. * Mental Retardation. * Anything that would interfere with assessments or study treatment or contraindicate study treatment. * Plans to move requiring school change during the next 4 months. * Antipsychotic agent in the 6 months prior to baseline assessment, fluoxetine or atomoxetine in the 4 weeks prior to baseline, stimulant in the week prior to baseline, or other psychiatric medication in the two weeks prior to baseline. * Previous neurofeedback training of more than 5 treatments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Double-blind, Sham-controlled Design #1. Recruitment Number | 2 years | The feasibility of the double-blind, sham-controlled design was examined in 3 ways, this first way was via the number of participants recruited. |
| Feasibility of Double-blind, Sham-controlled Design #2. Retention | 40th treatment sessions ~ 13-20 weeks | The feasibility of the double-blind, sham-controlled design was examined in 3 ways. The second way was via the percentage of participants retained the end of treatment (40th session). |
| Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Post-treatment at session 40 | The feasibility of the double-blind, sham-controlled design was examined in 3 ways. The 3rd way was the percentage of child and parent post-hoc guess regarding treatment assignment. |
| Frequency Advisability Outcome (2X vs. 3X/wk) #1 Parent & Child Satisfaction | 24 treatments ~ 8-12 weeks | Parent & child satisfaction of treatment frequency (x2 vs x3 treatments per week) was measured on a likert scale with anchors 0 (indicating low satisfaction) and 7 (indicating high satisfaction). |
| Frequency Advisability Outcome (2X vs. 3X/wk) #2. Treatment Frequency Choice | 24 treatments ~ 8-12 weeks | Treatment frequency preference when given choice to change or not to change treatment frequency from 2 to 3X/wk or 3 to 2X/wk at treatment # 24. |
| Necessary Duration of Treatment | 40 treatment sessions ~ 13-20 weeks | The necessary duration of treatments was examined via identifying the number of treatments at which improvement stabilized, as shown visually on graphs of parent-rated ADHD symptoms from the SNAP-IV (0-3 scale, lower score is better) for those participants in the Active Neurofeedback who completed 40 treatment sessions.The Sham group is not included in this outcome. |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment: August 2008 to December 2009. Location: Nisonger Center, OSU Medical Center
Pre-assignment details
Exclusion criteria: IQ \<80, mental age \<6, comorbid disorder or a medical disorder requiring medication that had psychoactive effects, \>5 previous NF treatments, antipsychotic medication within 6 mths pre-baseline, fluoxetine/atomoxetine 4-wks pre-baseline, stimulant 1-wk pre-baseline, or any other psychotropic medication 2-wks pre-baseline.
Participants by arm
| Arm | Count |
|---|---|
| Active Neurofeedback In the active neurofeedback condition, subjects will receive accurate neurofeedback either twice weekly vs. three times a week, with the same amount of total treatment over 40 sessions, varying only in frequency. | 26 |
| Sham Neurofeedback The sham condition will appear identical to the neurofeedback in all aspects: equipment, duration, frequency, and videogame choices. The only difference is that the interface module will be pre-programmed to give random feedback rather than contingent on the participant's brainwave power spectrum. | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Distance to center, poor grades | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Pursue medications | 1 | 2 |
Baseline characteristics
| Characteristic | Sham Neurofeedback | Active Neurofeedback | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 26 Participants | 39 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.7 years STANDARD_DEVIATION 2.1 | 9.0 years STANDARD_DEVIATION 1.5 | 8.9 years STANDARD_DEVIATION 1.8 |
| Region of Enrollment United States | 13 participants | 26 participants | 39 participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 22 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 13 |
| serious Total, serious adverse events | 0 / 26 | 0 / 13 |
Outcome results
Primary
Feasibility of Double-blind, Sham-controlled Design #1. Recruitment Number
The feasibility of the double-blind, sham-controlled design was examined in 3 ways, this first way was via the number of participants recruited.
Time frame: 2 years
Population: Based on inclusion \& exclusion criteria and randomization in a 2:1 ratio to active NF vs. sham NF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #1. Recruitment Number | 26 participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #1. Recruitment Number | 13 participants |
Primary
Feasibility of Double-blind, Sham-controlled Design #2. Retention
The feasibility of the double-blind, sham-controlled design was examined in 3 ways. The second way was via the percentage of participants retained the end of treatment (40th session).
Time frame: 40th treatment sessions ~ 13-20 weeks
Population: Number randomized was denominator for percentage of participants completing 40 treatment sessions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #2. Retention | 92.3 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #2. Retention | 76.9 percentage of participants |
Primary
Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind
The feasibility of the double-blind, sham-controlled design was examined in 3 ways. The 3rd way was the percentage of child and parent post-hoc guess regarding treatment assignment.
Time frame: Post-treatment at session 40
Population: Participants in both Active and Sham Neurofeedback completing 40 treatment sessions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Incorrect guesses by parent | 47 percentage of participants |
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Declined to guess by children | 35 percentage of participants |
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Declined to guess by parent | 29 percentage of participants |
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Correct guesses by children | 32 percentage of participants |
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Correct guesses by parents | 24 percentage of participants |
| Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Incorrect guesses by children | 32 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Correct guesses by parents | 24 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Incorrect guesses by parent | 47 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Correct guesses by children | 32 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Declined to guess by children | 35 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Incorrect guesses by children | 32 percentage of participants |
| Sham Neurofeedback | Feasibility of Double-blind, Sham-controlled Design #3. Validity of Blind | Declined to guess by parent | 29 percentage of participants |
Primary
Frequency Advisability Outcome (2X vs. 3X/wk) #1 Parent & Child Satisfaction
Parent & child satisfaction of treatment frequency (x2 vs x3 treatments per week) was measured on a likert scale with anchors 0 (indicating low satisfaction) and 7 (indicating high satisfaction).
Time frame: 24 treatments ~ 8-12 weeks
Population: Those completing 24 treatments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #1 Parent & Child Satisfaction | x2 wk Satisfaction | 5.21 units on a scale | Standard Deviation 1.8 |
| Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #1 Parent & Child Satisfaction | x 3/wk Satisfaction | 5.62 units on a scale | Standard Deviation 1.27 |
| Sham Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #1 Parent & Child Satisfaction | x2 wk Satisfaction | 5.40 units on a scale | Standard Deviation 1.07 |
| Sham Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #1 Parent & Child Satisfaction | x 3/wk Satisfaction | 5.08 units on a scale | Standard Deviation 1.73 |
Primary
Frequency Advisability Outcome (2X vs. 3X/wk) #2. Treatment Frequency Choice
Treatment frequency preference when given choice to change or not to change treatment frequency from 2 to 3X/wk or 3 to 2X/wk at treatment # 24.
Time frame: 24 treatments ~ 8-12 weeks
Population: participants completing treatment 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #2. Treatment Frequency Choice | % participants changing from x2-3 treatments/week | 44 percentage of participants |
| Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #2. Treatment Frequency Choice | % participants changing from x3-2 treatments/week | 22 percentage of participants |
| Sham Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #2. Treatment Frequency Choice | % participants changing from x2-3 treatments/week | 44 percentage of participants |
| Sham Neurofeedback | Frequency Advisability Outcome (2X vs. 3X/wk) #2. Treatment Frequency Choice | % participants changing from x3-2 treatments/week | 22 percentage of participants |
Primary
Necessary Duration of Treatment
The necessary duration of treatments was examined via identifying the number of treatments at which improvement stabilized, as shown visually on graphs of parent-rated ADHD symptoms from the SNAP-IV (0-3 scale, lower score is better) for those participants in the Active Neurofeedback who completed 40 treatment sessions.The Sham group is not included in this outcome.
Time frame: 40 treatment sessions ~ 13-20 weeks
Population: Number of participants in active (n=24) and sham (n=10) neurofeedback completing 40 treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Baseline | 1.91 units on a scale | Standard Deviation 0.51 |
| Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Treatment 12 | 1.52 units on a scale | Standard Deviation 0.63 |
| Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Treatment 24 | 1.48 units on a scale | Standard Deviation 0.6 |
| Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Treatment 40 | 1.56 units on a scale | Standard Deviation 0.7 |
| Sham Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Treatment 12 | 1.51 units on a scale | Standard Deviation 0.46 |
| Sham Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Baseline | 1.86 units on a scale | Standard Deviation 0.44 |
| Sham Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Treatment 40 | 1.42 units on a scale | Standard Deviation 0.58 |
| Sham Neurofeedback | Necessary Duration of Treatment | SNAP-IV Score Total at Treatment 24 | 1.56 units on a scale | Standard Deviation 0.52 |