TY - JOUR
T1 - Rationale and design of an international randomized placebo-controlled trial of a 36-ingredient micronutrient supplement for children with ADHD and irritable mood
T2 - The Micronutrients for ADHD in Youth (MADDY) study
AU - Johnstone, Jeanette M.
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
N1 - Funding Information:
Dr. Arnold has received research funding from Forest, Lilly, Noven, Shire, Supernus, Roche, and YoungLiving (as well as NIH and Autism Speaks); has consulted with Pfizer, Tris Pharma, and Waypoint; and been on advisory boards for Arbor, Ironshore, Otsuka, Pfizer, Roche, Seaside Therapeutics, Shire. Dr. Gracious has been or is a consultant to: AstraZeneca, Otsuka, and NovoNordisc. The other authors declare that they have no competing interests.
Funding Information:
Funding for the study has come through private donations to the Nutrition and Mental Health Research Fund, managed by the Foundation for Excellence in Mental Health Care (FEMHC) , as well as from a direct grant from FEMHC and funding from the Wells Fargo /Gratis Foundation. Dr. Johnstone is currently supported by an NIH-NCCIH 5R90AT00892403 through the National University for Natural Medicine. Dr. Johnstone's work on study inception and design was funded by NIH-NCCIH T32 AT002688 , as well as through support from the Department of Child and Adolescent Psychiatry, Oregon Health & Science University and Oregon Clinical & Translational Research, through the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128 . Dr. Gracious' time in assisting in study development was supported by the Jeffrey Research Fellowship, The OSU Dept. of Psychiatry & Behavioral Health ; The Ohio State University Center for Clinical and Translational Science award ( National Center for Advancing Translational Sciences , Grant 8UL1TR000090-05 ); and Dept. of Behavioral Health & Psychiatry, Nationwide Children's Hospital . The study at the Canadian site is funded by the Nutrition and Mental Health Research Fund, administered by the Calgary Foundation . Dr. Leung's position is supported by the Emmy Droog (endowed) chair in Complementary and Alternative Healthcare.
Funding Information:
Funding for the study has come through private donations to the Nutrition and Mental Health Research Fund, managed by the Foundation for Excellence in Mental Health Care (FEMHC), as well as from a direct grant from FEMHC and funding from the Wells Fargo/Gratis Foundation. Dr. Johnstone is currently supported by an NIH-NCCIH 5R90AT00892403 through the National University for Natural Medicine. Dr. Johnstone's work on study inception and design was funded by NIH-NCCIH T32 AT002688, as well as through support from the Department of Child and Adolescent Psychiatry, Oregon Health & Science University and Oregon Clinical & Translational Research, through the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128. Dr. Gracious' time in assisting in study development was supported by the Jeffrey Research Fellowship, The OSU Dept. of Psychiatry & Behavioral Health; The Ohio State University Center for Clinical and Translational Science award (National Center for Advancing Translational Sciences, Grant 8UL1TR000090-05); and Dept. of Behavioral Health & Psychiatry, Nationwide Children's Hospital. The study at the Canadian site is funded by the Nutrition and Mental Health Research Fund, administered by the Calgary Foundation. Dr. Leung's position is supported by the Emmy Droog (endowed) chair in Complementary and Alternative Healthcare.
Publisher Copyright:
© 2019 The Authors
PY - 2019/12
Y1 - 2019/12
N2 - 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
AB - 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
KW - ADHD
KW - Irritability
KW - Micronutrients
KW - Minerals
KW - Vitamins
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U2 - 10.1016/j.conctc.2019.100478
DO - 10.1016/j.conctc.2019.100478
M3 - Article
AN - SCOPUS:85074766267
VL - 16
JO - Contemporary Clinical Trials Communications
JF - Contemporary Clinical Trials Communications
SN - 2451-8654
M1 - 100478
ER -