Effectiveness of a Personalized Neurofeedback Training Device (ADHD@Home) in Attention-Deficit/Hyperactivity Disorder

Study Overview
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Brief Summary
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The main objective of the study is to demonstrate the non-inferiority of the personalized Neurofeedback Training device versus Methylphenidate in the treatment of children and adolescents with Attention-Deficit/Hyperactivity Disorder.

Detailed Description
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The main objective of the present study is to demonstrate the non-inferiority of the personalized Neurofeedback Training device ADHD@Home versus Methylphenidate in the treatment of children and adolescents with Attention-Deficit/Hyperactivity Disorder. Furthermore, it is aimed to learn more about the mechanisms underlying NeuroFeedback. The study is prospective, multicentric (9 centres), randomised, reference drug-controlled. ADHD@Home is a neuromarkerTM-based personalized medicine device to treat children suffering from Attention Deficit Hyperactivity Disorders (ADHD) with Neurofeedback Training (NFT) based on real time electroencephalography (EEG) signal. Neurofeedback Training is based on direct training of brain function, by which the brain learns to function more efficiently. For each session of the ADHD@Home solution, the child is trained to modulate his brain activity in a serious game, which is a real-time metaphor of the EEG biomarker that needs to be 'normalized', following a typical operant learning process.

Official Title
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Effectiveness of a Personalized Neurofeedback Training Device (ADHD@Home) as Compared With Methylphenidate in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Multicentre Randomized Clinical Study

Conditions
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Attention Deficit-Hyperactivity Disorder

Intervention / Treatment
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* Device: Neurofeedback NFT
* Drug: Methylphenidate MPH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children or adolescents (male or female) aged 7-13 years ADHD diagnosis positive with Kiddie-Sads ADHD RS IV >6 for attention, with or without hyperactivity Patient having already had corrective actions for ADHD (formal and informal educational support, psychoeducation, psychotherapy, occupational therapy remediation, at-school programs and remediations) Signature of inform consent form by parent and child Wireless internet connection at home Exclusion Criteria: ADHD hyperactive/Impulsive without inattention component Established diagnosis of epilepsy or other neurological disorders Severe and/or uncontrolled psychiatric disorder other than ADHD diagnosed with Kiddie-Sads such as autism, schizophrenia, severe generalized anxiety disorder, major depression or severe tics Patient with comorbid disorder requiring psychoactive medication other than ADHD medication Patient having already been treated with psycho-active drug (MPH and others) or EEG-NF for ADHD in the last 6 months, or more than 4 weeks more than 6 months ago Unable to use the solution (tablet use and/or headset set-up and/or understanding instructions) according to the investigator Absence of wireless internet connection at home Medical disorder requiring systemic chronic medication with confounding psychoactive effects IQ < 80 using the 3 subtest form of the WASI or the WISC Plans to move requiring centre change during the next 6 months Plans to start other ADHD treatment, including psychotherapy, cognitive behaviour training in the next 6 months Patient with chronic medical illness such as seizure, cardiac disorders, untreated thyroid disease or glaucoma (contra-indication for treatment with MPH) Significant suicidal risk based on clinical opinion Patient with prescribed dietary interventions Patient with a known hypersensitivity to one of the ingredients of the investigational products

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neurofeedback NFT<br>Neurofeedback Training based on real time electroencephalography (EEG) signal. The patient is trained to modulate his brain activity thanks to a tablet installed with serious game. Initiation/Discovery period during 21 days: initiation and discovery sessions Treatment period during 9 weeks: 36 training sessions at home | Device: Neurofeedback NFT<br>* The ADHD@Home Device is composed of a software for NF Training deployed on a Windows tablet, and connected to an EEG headset and an amplifier. The training is personalized according to patient's characteristics.<br>* Other names: ADHD@Home;|
| Active Comparator: Methylphenidate MPH<br>Methylphenidate long acting preparation. Open titration protocol during 21 days: 10 mg/day as a start until optimal dose is reached (maximum dose: 60 mg/day). Treatment period during 9 weeks: optimal dose with MPH LA 10 and 30 mg (dose range: 10 mg/day to 60 mg/day). | Drug: Methylphenidate MPH<br>* Drug prescribed with a first titration period until an optimal dose.<br>* Other names: Medikinet retard;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Day 0 at Day 90 of the total score of the ADHD RS IV (Attention Deficit Hyperactivity Disorder Rating Scale IV) | ADHD RS IV (Attention Deficit Hyperactivity Disorder Rating Scale IV): total score assessed by the clinician | 3 times (Day 0, Day 60, Day 90) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADHD RS IV Inattention and Hyperactivity Sub-Scores | ADHD RS IV (Attention Deficit Hyperactivity Disorder Rating Scale IV): Inattention and Hyperactivity sub-scores assessed by the clinician | 3 times (Day 0, Day 60, Day 90) | 
| Clinical responders | Clinical responders are subjects who will present a decrease of the total clinician ADHD RS score of more or equal to 25% | 1 time (Day 90) | 
| Parents ADHD RS IV Total, Inattention and Hyperactivity Scores | ADHD RS IV (Attention Deficit Hyperactivity Disorder Rating Scale IV): Total, Inattention and Hyperactivity scores assessed by the parents | 3 times (Day 0, Day 60, Day 90) | 
| Teacher ADHD RS IV Total, Inattention and Hyperactivity Scores | ADHD RS IV (Attention Deficit Hyperactivity Disorder Rating Scale IV): Total, Inattention and Hyperactivity scores assessed by the teacher | 2 times (Day 0, Day 90) | 
| Clinical Global Impression (severity) (CGI-S) | Severity of the illness assessed by the clinician | 7 times (Day 0, Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Clinical Global Impression (improvement) (CGI-I) | Improvement of the patient's condition assessed by the clinician | 6 times (Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Behavior Rating Inventory of Executive Function (BRIEF) | Executive Function Tests by the Behavior Rating Inventory of Executive Function (BRIEF) | 2 times (Day 0, Day 90) | 
| Conners Continuous Performance Test 3rd Edition (Conners CPT 3) | Conners Continuous Performance Test 3rd Edition | 2 times (Day 0, Day 90) | 
| Strengths and Difficulties Questionnaire (SDQ) | Behaviour assessment by the parents and the teacher with the Strengths and Difficulties Questionnaire | 2 times (Day 0, Day 90) | 
| quantitative Electro-Encephalogram (qEEG) | Quantitative electroencephalogram to assess EEG biomarkers, progress in brain modulation | 3 times (Day 0, Day 60, Day 90) | 
| Columbia suicide severity rating scale (C-SSRS) | Columbia suicide severity rating scale | 7 times (Day 0, Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Sleep Disturbance Scale for Children (SDSC) | Sleep Disturbance Scale for Children | 7 times (Day 0, Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Pediatric adverse event rating scale (PAERS) | Pediatric adverse event rating scale | 7 times (Day 0, Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Physical examination | Physical examination will include assessments of height, weight, cardiac frequency, cardiac exam and blood pressure. Investigator will question the parents about the cardiac history of the family and on individual risk factors. If a risk factor is detected, the patient will be addressed to a cardiologist for an electrocardiogram (ECG). | 1 time (Day 0) | 
| Medical/surgical history | Assessment especially related to the eligibility criteria | 1 time (Day 0) | 
| Concomitant treatments collection | All the treatments taken during the participation will be collected (trade name, indication, dose, onset/end dates). The use of concomitant medications will be summarized by therapeutic class. | 7 times (Day 0, Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Adverse events collection | All the adverse events occurred during the participation will be collected until resolution or stabilization (description/symptoms, onset/end dates, frequency, intensity, evolution, causality to treatment attributed, seriousness). All adverse events will be described in each arm. A comparison will be done, especially concerning number and percentage of patients who experienced at least one adverse event (on the whole and by system/organ), at least one adverse event leading to discontinue the treatment, and at least one serious adverse event. | 6 times (Day 7, Day 14, Day 21, Day 28, Day 60, Day 90) | 
| Child Health and Illness Profile, Child Edition (CHIP-CE) | Measure of the quality of life by the parents with the CHIP-CE parents report form | 2 times (Day 0, Day 90) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attention deficit, Neurofeedback, ADHD, Methylphenidate