Search

Background Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. Methods This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. Discussion This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Trial registration Clinicaltrials.gov number: NCT02700685. Registered on 18 January 2016. EudraCT 2016-000215-32. Registered on 4 October 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1879-6) contains supplementary material, which is available to authorized users.

Background Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can negatively impact on an individual’s quality of life. It is pathophysiologically complex and heterogeneous with different neuropsychological processes being impaired in different individuals. Executive function deficits, including those affecting attention, working memory and inhibitory control, are common. Cognitive training has been promoted as a treatment option, based on the notion that by strengthening the neurocognitive networks underlying these executive processes, ADHD symptoms will also be reduced. However, if implemented in childhood or later, when the full disorder has become well-established, cognitive training has only limited value. INTERSTAARS is a trial designed to test a novel approach to intervention, in which cognitive training is implemented early in development, before the emergence of the disorder. The aim of INTERSTAARS is to train early executive skills, thereby increasing resilience and reducing later ADHD symptoms and associated impairment. Methods/design Fifty 10–14-month-old infants at familial risk of ADHD will participate in INTERSTAARS. Infants will be randomised to an intervention or a control group. The intervention aims to train early attention skills by using novel eye-tracking technology and gaze-contingent training paradigms. Infants view animated games on a screen and different events take place contingent on where on the screen the infant is looking. Infants allocated to the intervention will receive nine weekly home-based attention training sessions. Control group infants will also receive nine weekly home visits, but instead of viewing the training games during these visits they will view non-gaze-contingent age-appropriate videos. At baseline and post treatment, infant attention control will be assessed using a range of eye-tracking, observational, parent-report and neurophysiological measures. The primary outcome will be a composite of eye-tracking tasks used to assess infant attention skills. Follow-up data will be collected on emerging ADHD symptoms when the infants are 2 and 3 years old. Discussion This is the first randomised controlled trial to assess the potential efficacy of cognitive training as a prevention measure for infants at familial risk of ADHD. If successful, INTERSTAARS could offer a promising new approach for developing early interventions for ADHD. Trial registration International Standard Randomised Controlled Trial registry: ISRCTN37683928. Registered on 22 June 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1727-0) contains supplementary material, which is available to authorized users.