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

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Article number100478
JournalContemporary Clinical Trials Communications
Volume16
DOIs
StatePublished - Dec 2019

Fingerprint

Irritable Mood
Micronutrients
Attention Deficit Disorder with Hyperactivity
Randomized Controlled Trials
Placebos
Attention Deficit and Disruptive Behavior Disorders
Mood Disorders
Equipment and Supplies
Anger
Therapeutics
North America
Aggression
Saliva
Vitamins
Hair
Antipsychotic Agents
Prescriptions
Minerals
Epidemiology
Clinical Trials

Keywords

  • ADHD
  • Irritability
  • Micronutrients
  • Minerals
  • Vitamins

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

In: Contemporary Clinical Trials Communications, Vol. 16, 100478, 12.2019.

Research output: Contribution to journalArticle

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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",
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AU - Leung, Brenda

AU - Gracious, Barbara

AU - Perez, Leanna

AU - Tost, Gabriella

AU - Savoy, Andrew

AU - Hatsu, Irene

AU - Hughes, Andrew

AU - Bruton, Alisha

AU - Arnold, L. Eugene

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