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

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

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.

Study Overview

• Status: Unknown
• Conditions: Attention Deficit-Hyperactivity Disorder
• Intervention / Treatment: Device: Neurofeedback NFT; Drug: Methylphenidate MPH

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 179
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Michel Du Peloux, PhD; Phone Number: +33 062-434-1061; Email: michel.du-peloux@mensiatech.com

Study Locations

• Belgium
  • Bruxelles, Belgium, 1080
    • Recruiting
    • PSY Pluriel Centre europeen de psychologie medicale
    • Contact: Laurent Victoor, MD/PhD; Phone Number: +32 (0)2331-5665; Email: lvictoor@psypluriel.be
    • Contact: Daniel Souery, MD/PhD; Phone Number: +32 (0)2331-5665; Email: dsouery@psypluriel.be
    • Principal Investigator: Laurent Victoor, MD/PhD
  • Bruxelles, Belgium, B-1070
    • Not yet recruiting
    • Hopital Erasme - Cliniques Universitaires de Bruxelles
    • Contact: Marie Delhaye, MD, PhD; Phone Number: +32 (0)2 555 37 30; Email: Marie.Delhaye@erasme.ulb.ac.be
    • Contact: Kristell Ackerman, MD, PhD; Phone Number: +32 (0)2 555 35 96; Email: kristell.ackerman@erasme.ulb.ac.be
    • Principal Investigator: Marie Delhaye, MD, PhD
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Centre Hospitalier Charles Perrens
    • Contact: Stephanie Bioulac, MD/PhD; Email: stephanie.bioulac@chu-bordeaux.fr
    • Principal Investigator: Stephanie Bioulac, MD/PhD
  • Lille, France, 59000
    • Recruiting
    • CHRU de Lille - Hôpital Fontan - Service de psychiatrie de l'enfant et de l'adolescent
    • Contact: Renaud Jardri, Pr; Email: Renaud.JARDRI@chru-lille.fr
    • Contact: Aesa Parenti, MD, PhD; Phone Number: +33 (0)3 20 44 67 47; Email: AESA.PARENTI@chru-lille.fr
    • Principal Investigator: Renaud Jardri, Pr
  • Lille, France, 59120
    • Recruiting
    • Clinique Lautréamont
    • Contact: Frederic Kochman, MD/PhD; Phone Number: +33 (0)82-610-9990; Email: f.kochman@orpea.net
    • Principal Investigator: Frederic Kochman, MD/PhD
  • Lyon, France, 59003
    • Recruiting
    • Hospice Civil de Lyon - Hôpital Neurologique Service de Neuro-Psychiatrie de l'Enfant
    • Contact: Olivier Revol, MD, PhD; Email: olivier.revol@chu-lyon.fr
    • Principal Investigator: Olivier Revol, MD, PhD
  • Montpellier, France, 34000
    • Recruiting
    • CHRU Montpellier
    • Contact: Diane Purper-Ouakil, MD/PhD; Phone Number: +33 (0)4 67 33 60 09; Email: d-purper_ouakil@chu.montpellier.fr
    • Principal Investigator: Diane Purper-Ouakil, MD/PhD
• Germany
  • Mannheim, Germany, 68159
    • Not yet recruiting
    • Medical faculty of Mannheim/Heidelberg university
    • Contact: Daniel Brandeis, DSc/Pr; Phone Number: +49 (0)621 1703 4922; Email: daniel.brandeis@zi-mannheim.de
    • Contact: Tobias Banaschewski, MD/PhD
    • Principal Investigator: Tobias Banaschewski, MD/PhD
  • Bayern
    • Erlangen, Bayern, Germany, 91052
      • Terminated
      • Universitätklinikum Erlangen
• Spain
  • Madrid, Spain, 28400
    • Recruiting
    • Puerta de Hierro Hospital - Department of Psychiatry
    • Contact: Hilario Blasco-Fontecilla, MD/PhD; Phone Number: +34 (0)91 8503008; Email: hmblasco@yahoo.es
    • Principal Investigator: Hilario Blasco-Fontecilla, MD/PhD
• Switzerland
  • Genève, Switzerland, 1206
    • Not yet recruiting
    • Clinique des Grangettes
    • Contact: Caroline C Menache, MD/PhD; Phone Number: +41 (0)22 305 0567; Email: caroline.menache@grangettes.ch
    • Principal Investigator: Caroline Menache, MD/PhD
  • Zürich, Switzerland, CH- 8032
    • Not yet recruiting
    • Psychiatric Hospital, University of Zürich
    • Contact: Daniel Brandeis, MSc/Pr; Phone Number: +41 (0)43 499 2763; Email: brandeis@kjpd.uzh.ch
    • Contact: Susanne Walitza, MD/MSc/Pr; Phone Number: +41 (0)43 499 27 30; Email: susanne.walitza@puk.zh.ch
    • Principal Investigator: Susanne Walitza, MD/MSc/Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neurofeedback NFT; 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; 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.; Other Names: Neurofeedback training; ADHD@Home
Active Comparator: Methylphenidate MPH; 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; Drug prescribed with a first titration period until an optimal dose.; Other Names: Medikinet retard; Methylphenidate long acting

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Mensia Technologies SA
• Collaborators: European Union H2020 SME Instrument
• Investigators: Study Director: Michel Du Peloux, PhD, Mensia Technologies; Principal Investigator: Diane Purper-Ouakil, MD/PhD, CHRU Montpellier

Publications and helpful links

General Publications

• Purper-Ouakil D, Blasco-Fontecilla H, Ros T, Acquaviva E, Banaschewski T, Baumeister S, Bousquet E, Bussalb A, Delhaye M, Delorme R, Drechsler R, Goujon A, Hage A, Kaiser A, Mayaud L, Mechler K, Menache C, Revol O, Tagwerker F, Walitza S, Werling AM, Bioulac S, Brandeis D. Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial. J Child Psychol Psychiatry. 2022 Feb;63(2):187-198. doi: 10.1111/jcpp.13462. Epub 2021 Jun 24.
• Bioulac S, Purper-Ouakil D, Ros T, Blasco-Fontecilla H, Prats M, Mayaud L, Brandeis D. Personalized at-home neurofeedback compared with long-acting methylphenidate in an european non-inferiority randomized trial in children with ADHD. BMC Psychiatry. 2019 Aug 1;19(1):237. doi: 10.1186/s12888-019-2218-0.

Helpful Links

• Opinons on NFT for ADHD

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: May 12, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimate): May 19, 2016

Study Record Updates

• Last Update Posted (Actual): April 5, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: ADHD; Neurofeedback; Methylphenidate; Attention deficit
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: Newrofeed

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided