Journal Article

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)

Johansson, Lena, Rubia, Katya, Cortese, Samuele, Carter, Ben, Santosh, Paramala, Mehta, Mitul A., Bozhilova, Natali, Stringer, Dominic, Eraydin, Irem Ece, Conti, Aldo Alberto

2024

Overview

Background Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action. Methods A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment. Discussion This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD. Trial registration : ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: ADHD / Adolescent / Attention Deficit Disorder with Hyperactivity - therapy / Attention deficit hyperactivity disorder / Attention-Deficit / Brain / Child / Children & youth / Clinical trials / Clinical Trials, Phase II as Topic / Cognition & reasoning / Double-Blind Method / Drug therapy / eTNS / Executive function / External trigeminal nerve stimulation / FDA approval / Female / Heart rate / Humans / Hyperactivity / Hyperactivity Disorder / Magnetic resonance imaging / Male / Medicine / Medicine & Public Health / Memory / Multicenter Studies as Topic / Neuroimaging / Neuromodulation / Parents & parenting / Physiology / Psychiatry / Psychotherapy / Questionnaires / Randomized Controlled Trials as Topic / Side effects / Study Protocol / Treatment Outcome / Trigeminal Nerve / Trigeminal nerve stimulation