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:
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:
To develop the Micronutrients for ADHD in Youth (MADDY) Study protocol, an international consortium of experts in ADHD, nutrition, and clinical trials conferred by email and weekly teleconference for more than a year. The decision to focus on irritability and anger as a feature of ADHD was guided by previous research in children and adults indicating that irritability and mood dysregulation improved as much or more than core ADHD symptoms micronutrient treatment [ 38 , 41 ]. An Investigational New Drug (IND) application was submitted to the United States Food and Drug Administration (FDA), and was approved after review of micronutrient supplement analyses; approval of the study and the micronutrient use was also granted by Health Canada. Dr. Barbara Gracious at The Ohio State (OSU), holds IND#127832. The study protocol was approved by the respective Institutional Review Boards at OHSU, OSU, and the University of Calgary Conjoint Health Research Ethics Board, for the University of Lethbridge (U of L). Hardy Nutritionals (Raymond, Alberta, Canada) provided a letter of agreement for donated research product (Daily Essential Nutrients, “DEN”) and matching placebo supply. No financial support was provided by the company, and they have relinquished rights to any data ownership, analyses, or publications.
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.
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.
KW - ADHD
KW - Irritability
KW - Micronutrients
KW - Minerals
KW - Vitamins
UR - http://www.scopus.com/inward/record.url?scp=85074766267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074766267&partnerID=8YFLogxK
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 -