Journal Article

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial

De Bruyne, Tess, Ceulemans, Berten, Van West, Dirk, Verhelst, Helene, Hermans, Nina, Verlaet, Annelies A. J., Savelkoul, Huub F. J., Pieters, Luc

2017

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ADD / ADHD / Adjuvants, Immunologic - adverse effects / Adjuvants, Immunologic - therapeutic use / Analysis / Antioxidant / Antioxidants / Antioxidants - adverse effects / Antioxidants - therapeutic use / Attention Deficit Disorder with Hyperactivity - drug therapy / Attention Deficit Disorder with Hyperactivity - immunology / Attention Deficit Disorder with Hyperactivity - metabolism / Attention Deficit Disorder with Hyperactivity - psychology / Attention deficit hyperactivity disorder / Autism / Behaviour / Belgium / Biomarkers / Biomarkers - blood / Biomarkers - urine / Biomedicine / Blood pressure / Caregivers / Catecholamines / Central Nervous System Stimulants - adverse effects / Central Nervous System Stimulants - therapeutic use / Child / Child Behavior - drug effects / Clinical Protocols / Clinical trials / Comorbidity / Complications and side effects / Consent / Cytokines - blood / Double-Blind Method / Drug therapy / Enzymes / Face - microbiology / Feeding Behavior / Female / Flavonoids - adverse effects / Flavonoids - therapeutic use / Health Sciences / Humans / Hyperactivity / Immunity / Impulsivity / Male / Medicine / Medicine & Public Health / Methylphenidate - adverse effects / Methylphenidate - therapeutic use / Oxidative stress / Oxidative Stress - drug effects / Patients / Pediatrics / Plant Extracts / Polyphenols / Pycnogenol / Questionnaires / Research Design / Statistics for Life Sciences / Study Protocol / Surveys and Questionnaires / Time Factors / Treatment Outcome