Verlaet 2017.

Study name	Public title: Effect of Pycnogenoll® on ADHD Scientific title: Effect of Pycnogenoll® on attention‐deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial
Methods	Randomised, double‐blind, placebo‐ and active treatment‐controlled multicentre trial, with 3 parallel treatment arms Study duration: 10 weeks
Participants	Sample size (actual): 144 Inclusion criteria Patient is between 6‐12 years old (both inclusive) Patient satisfies the DSM‐IV criteria for ADHD or ADD Patient has a responsible caregiver who is able to provide information about the patient's functional status Written informed consent is obtained from the patient and the legally accepted representative Exclusion criteria Autism spectrum disorder according to DSM‐IV Situational hyperactivity, pervasive developmental disorders, schizophrenia, other psychotic disorders such as mood or anxiety disorder, personality disorder, unsocial behaviour, personality change due to a general medical condition, mental disability (IQ < 70), understimulating environments, CD, chorea and other dyskinesias, tics or Tourette's syndrome Personal or family history of psychotic disorder, bipolar illness, depression, or suicide attempt Any chronic medical disorder (diabetes, epilepsy or other seizure disorder, autoimmune disorder, gastrointestinal disorder, renal or cardiovascular disorders, etc.) or acute inflammatory disease Glaucoma, heart disease, heart rhythm disorder, high blood pressure, or peripheral vascular disease such as Raynaud's syndrome Use of clonidine, guanethidine, blood thinners (e.g. warfarin or Coumadin), antidepressants (e.g. amitriptyline, citalopram, doxepin, fluoxetine, nortriptyline, paroxetine, sertraline), cold or allergy medicine at any point in the 3 months prior to entering the study Use of MAOI (isocarboxazid, linezolid, phenelzine, rasagiline, selegiline or tranylcypromine) in the past 14 days Any contraindication for the use of MPH Use of vitamin/mineral/herbal/omega‐3 supplements or other any medication (psychoactive medication, antibiotics, anti‐inflammatory drugs, melatonin, etc.) > 1 week during the 3 months before inclusion
Interventions	MPH Pycnogenol Placebo
Outcomes	ADHD symptoms ADHD‐RS. Assessed at baseline, week 5 and 10 SEQ. Assessed at baseline, and week 10 General behaviour Social behavior problems subscale of the SEQ. Assessed at baseline, and week 10 Non‐serious AEs Immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition). Assessed at baseline, and week 10 Oxidative stress (erythrocyte glutathione, plasma lipid‐soluble vitamins and malondialdehyde and urinary 8‐OHdG levels, as well as antioxidant enzyme activity and gene expression). Assessed at baseline, and week 10 Serum zinc and neuropeptide Y level. Assessed at baseline, and week 10 Urinary catecholamines. Assessed at baseline, and week 10 Physical and sleep complaints (Physical Complaints Questionnaire). Assessed at baseline, week 5, and 10
Starting date	1 September 2017
Contact information	Name: Nina Hermans, PhD Affiliation: Department of Pharmaceutical Sciences, Laboratory of Nutrition and Functional Food Science, University of Antwerp, Belgium Email: Annelies.verlaet@uantwerpen.be
Notes	Sponsor: Fund for Scientific Research Flanders (Fonds Wetenschappelijk Onderzoek (FWO); FWO MAND 2013 ‐ 11U8316N 5 W) Declaration of interests: no competing interests declared

ADD: attention deficit disorder; ADHD: attention deficit hyperactivity disorder; AE: adverse event; ARI: Affective Reactivity Index scale; ASA: acetylsalicylic acid; ASQ(‐T)/(‐P): Conners' Abbreviated Symptom Questionnaire (for teachers/parents); CD: conduct disorder; CGAS: Child Global Assessment Scales; CGI: Clinical Global Impressions; CPRS: Conners' Parent Rating Scale; CPT: Continuous Performance Test; d‐MPH: dexmethylphenidate; DSM(‐IV/‐5):Diagnostic and Statistical Manual of Mental Disorders (‐Fourth Edition/Fifth Edition);ECG: electroencephalogram; ER‐MPH: extended‐release methylphenidate; EST: Eastern Standard Time; GMT: Greenwich Mean Time; IDS‐2: Intelligence and Development 2nd Version; IR‐MPH: immediate‐release methylphenidate; IQ: intelligence quotient; K‐SADS‐PL: Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime version; MAOI: monoamine oxidase inhibitor; MAP‐DB: Multidimensional Assessment Profile of Disruptive Behavior; MPH: methylphenidate; ODD: oppositional defiant disorder; PI: principal investigator
PICS: Parent Interview for Child Symptoms; QEEG: quantitative electroencephalography; RCT: randomised controlled trial; SBP: systolic blood pressure; SEQ: Social‐Emotional Questionnaire; SMS: Smith ‐ Magenis Syndrome; SNAP(‐IV): Swanson, Nolan and Pelham scale (Fourth Edition); UMC: University Medical Centre; UTC: Universal Time Coordinated; WISC‐III‐R: Wechsler Intelligence Scale for Children; 8‐OHdG: 8‐hydroxy‐2′‐deoxyguanosine