Clinical trial NCT03252522: Micronutrients for Attention-Deficit Hyperactivity Disorder in Youth (MADDY) Study
Official title: Evaluating the Efficacy of Supplementation With Micronutrients for ADHD in Youth (MADDY) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: ADHD
ODD
DMDD
Inattention
Impulsivity
Irritability
Anger
Micronutrients
Emotional Dysregulation
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Ohio State University
name: University of Lethbridge
name: National University of Natural Medicine
name: Foundation for Excellence in Mental Health Care
name: The Waterloo Foundation
First posted: 2017-08-17
Enrollment: 135
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This proposed research will use randomized control trial (RCT) methodology and compare micronutrients with placebo in 135 children with ADHD.

Detailed description: This study examines a broad spectrum micronutrient treatment for children with ADHD. The goal is to broaden the scope of evidence-based treatments, and to address the public desire for non-pharmacological treatment options. This study will use a randomized controlled trial design, comparing micronutrients with placebo in 135 children, ages 6-12, with ADHD plus irritability or anger based on parent-report of symptoms. The study will also collect biological samples (saliva, stool, urine, hair, and blood) from the children to examine physiological mechanisms of micronutrient effects. If the micronutrient treatment successfully diminishes symptoms, the clinical implication is to offer this as a legitimate non-pharmacological alternative to stimulant medication.

Eligibility criteria: Inclusion Criteria:

* Age inclusive of and between 6 and 12 years at the time of enrollment.
* Verbally willing to swallowing a maximum of 9-12 capsules/day with food, attend all study appointments and complete questionnaires.
* Meet criteria for ADHD as assessed by the clinical cut-off (6+ questions scored as 2's or 3's, "often," or "very often") on the Category A: ADHD questions from on the Child \& Adolescent Symptom Inventory-5 (CASI-5) with at least several symptoms present in more than one setting, based on the Diagnostic and Statistical Manual (DSM) 5 symptom criteria, including significant impairment in functioning socially and/or academically.
* Demonstrate at least one symptom of irritability or anger as assessed by a score of 2 or 3 on one question from Category B or Rz from the CASI-5.
* Be medication-free, or washout with medical supervision to be provided by the child's pediatrician or primary care physician, reliant on the parent/guardian to work with that physician, for at least two weeks prior to in-person study assessment. Washout will be recorded as occurring on the date reported by the parent/guardian, with a faxed copy of the progress note, visit summary or signed letter from participant's doctor.

Exclusion Criteria:

* Neurological disorder involving brain or other central function (e.g., history of or suspected intellectual disability, autism spectrum disorder, epilepsy, multiple sclerosis, narcolepsy) or other major psychiatric condition requiring hospitalization (e.g. significant mood disorder, active suicidal ideation, or psychosis), based on parent/guardian self-report of child's condition and responses to category M on the CASI-5 subscale.
* Any serious medical condition, including inflammatory bowel disease, history of cancer, kidney or liver disease, hyperthyroidism, diabetes Type I or II.
* Known allergy to any ingredients of the intervention.
* Any known abnormality of mineral metabolism (e.g., Wilson's disease, hemochromatosis).
* Taking any other medication with primarily central nervous system activity, including stimulants, within the last two weeks prior to in-person assessment; participants must be off these medications for a minimum of two weeks prior to the screening.
* Severe separation anxiety that would preclude separating from parent/guardian to answer study questionnaires.
* Any disability that would interfere with participant answering questions verbally.
* Non-English speaking.
* Pregnancy or sexually active at baseline. Exclusion criteria 1-6 and 9, will be based on parent/guardian self-report of child's condition. If the parent/guardian reports medical exclusion criteria, or concerns about eligibility, data provided by parent/guardian will be confirmed by review of medical records with release of information signed by parent/guardian. Potential participant may be reviewed in-person by a study physician in the case of any concerns about participation.

Primary outcomes:
measure: CASI-5 Parent-rated Composite Score
timeFrame: Baseline and week 8
measure: Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2)
timeFrame: Week 8
Secondary outcomes:
measure: Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L
timeFrame: Baseline and Week 8
measure: Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL
timeFrame: Baseline and Week 8
measure: Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL
timeFrame: Baseline and Week 8
measure: AST, ALT, Alkaline in U/L
timeFrame: Baseline and Week 8
measure: RBC Count in Cells/mcL
timeFrame: Baseline and Week 8
measure: Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent
timeFrame: Baseline and Week 8
measure: Mean Cell Volume in fL
timeFrame: Baseline and Week 8
measure: Iron in ug/dL
timeFrame: Baseline and Week 8
measure: WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL
timeFrame: Baseline and Week 8
measure: Clinical Global Impression (CGI)
timeFrame: 16 weeks
measure: CASI-5 Parent Report
timeFrame: Week 16
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Lethbridge
country: Canada
facility: University of Lethbridge
state: Alberta
Study officials:
affiliation: Oregon Health and Science University
name: Jeanette Johnstone
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leung BMY, Srikanth P, Gracious B, Hatsu IE, Tost G, Conrad V, Johnstone JM, Arnold LE. Paediatric adverse event rating scale: a measure of safety or efficacy? Novel analysis from the MADDY study. Curr Med Res Opin. 2022 Sep;38(9):1595-1602. doi: 10.1080/03007995.2022.2096333. Epub 2022 Jul 11.
citation: Johnstone JM, Hatsu I, Tost G, Srikanth P, Eiterman LP, Bruton AM, Ast HK, Robinette LM, Stern MM, Millington EG, Gracious BL, Hughes AJ, Leung BMY, Arnold LE. Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial. J Am Acad Child Adolesc Psychiatry. 2022 May;61(5):647-661. doi: 10.1016/j.jaac.2021.07.005. Epub 2021 Jul 22.
citation: Johnstone JM, Leung B, Gracious B, Perez L, Tost G, Savoy A, Hatsu I, Hughes A, Bruton A, Arnold LE. 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.