Rationale and design of an international randomized placebo-controlled trial of a 36-ingredient micronutrient supplement for children with ADHD and irritable mood: The Micronutrients for ADHD in Youth (MADDY) study

Jeanette M Johnstone; Brenda Leung; Barbara Gracious; Leanna Perez; Gabriella Tost; Andrew Savoy; Irene Hatsu; Andrew Hughes; Alisha Bruton; L Eugene Arnold

doi:10.1016/j.conctc.2019.100478

Rationale and design of an international randomized placebo-controlled trial of a 36-ingredient micronutrient supplement for children with ADHD and irritable mood: The Micronutrients for ADHD in Youth (MADDY) study

Contemp Clin Trials Commun. 2019 Oct 26:16:100478. doi: 10.1016/j.conctc.2019.100478. eCollection 2019 Dec.

Authors

Jeanette M Johnstone^{1

2}, Brenda Leung³, Barbara Gracious^{4

5}, Leanna Perez⁶, Gabriella Tost², Andrew Savoy², Irene Hatsu⁶, Andrew Hughes², Alisha Bruton^{1

2}, L Eugene Arnold⁴

Affiliations

¹ National University of Natural Medicine, Helfgott Research Institute, Portland, OR, USA.
² Department of Child & Adolescent Psychiatry, Oregon Health & Science University, Portland, OR, USA.
³ Faculty of Health Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
⁴ Department of Psychiatry & Behavioral Health, The Ohio State University, Columbus, OH, USA.
⁵ Orange Park Medical Center, Orange Park, FL, USA.
⁶ Department of Human Sciences, The Ohio State University, Columbus, OH, USA.

Abstract

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental disorder affecting up to 9% of children and substantial numbers of adults. Existing pharmacologic treatments often improve symptoms, but concerns exist over side effects, stigma, potential long-term health effects, and residual irritability, often treated with adjunctive antipsychotics. To address public and clinician demand for non-pharmacologic evidence-based treatments, this study will examine efficacy of a 36-ingredient micronutrient (vitamin/mineral) supplement as treatment for children with ADHD and irritability.

Methods: An international team of experts in ADHD, mood dysregulation, nutrition, epidemiology, and clinical trials conferred to develop/refine a protocol powered to detect a medium effect. The study will employ a fully-blind randomized controlled trial (RCT) design, comparing the micronutrient supplement to matched placebo in 135 children aged 6-12 with ADHD symptoms and irritability, based on the parent-rated Child and Adolescent Symptom Inventory-5 (CASI-5). Irritability will be measured by at least one symptom of oppositional defiant disorder (ODD) or disruptive mood dysregulation disorder (DMDD). Based on research suggesting an irritable ADHD subtype, the primary outcome will be a composite score comprised of the CASI-5 subscales: ADHD, ODD, DMDD, and the Peer Conflict Scale, which assesses anger and aggression perpetrated towards peers. Participants will provide biological samples (blood, urine, saliva, hair and stool) to explore the micronutrients' mechanisms of action.

Discussion: This study is the first adequately powered RCT in North America to examine both behavioral responses to, and biological mechanisms of, micronutrients for ADHD and irritability in children. If found efficacious, broad-spectrum micronutrients, given at therapeutic doses, may provide an evidence-based alternative to prescription medications for ADHD and associated irritability.

Trial registration: NCT03252522. Registered 26 July 2017.

Keywords: ADHD; Irritability; Micronutrients; Minerals; Vitamins.

Associated data

ClinicalTrials.gov/NCT03252522

Abstract

Associated data

Grants and funding