Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, ODD, DMDD, Inattention, Impulsivity, Irritability, Anger, Micronutrients, Emotional Dysregulation
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.
Interventions
COMBINATION_PRODUCTBroad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants
60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks
DIETARY_SUPPLEMENTPlacebo
40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.
Sponsors
Ohio State University
University of Lethbridge
National University of Natural Medicine
Foundation for Excellence in Mental Health Care
The Waterloo Foundation
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo-controlled; randomization created by statistician, all involved in the study and assessment are blinded
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CASI-5 Parent-rated Composite Score | Baseline and week 8 | Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5). The CASI-5 is based on the DSM-5 symptom criteria. The subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict that will be combined into a total composite score; range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. |
| Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2) | Week 8 | Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| AST, ALT, Alkaline in U/L | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| Iron in ug/dL | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| Clinical Global Impression (CGI) | 16 weeks | Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline. |
| CASI-5 Parent Report | Week 16 | Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5) subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict. The CASI-5 is based on the DSM-5 symptom criteria. Item range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. The subscales for ADHD, ODD, and DMD will be composite scores. |
| RBC Count in Cells/mcL | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
| Mean Cell Volume in fL | Baseline and Week 8 | Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks | 78 |
| Placebo Capsules of inactive placebo.
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks. | 57 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase 1: Intervention & Placebo | Adverse Event | 3 | 1 | 0 |
| Phase 1: Intervention & Placebo | Commenced stimulant medication | 1 | 1 | 0 |
| Phase 1: Intervention & Placebo | Protocol Violation | 1 | 0 | 0 |
| Phase 1: Intervention & Placebo | Unable to swallow pills | 4 | 1 | 0 |
| Phase 2: Open Label | Adverse Event | 0 | 0 | 2 |
| Phase 2: Open Label | Commenced stimulant medication | 0 | 0 | 3 |
| Phase 2: Open Label | Lack of Efficacy | 0 | 0 | 3 |
| Phase 2: Open Label | Lost to Follow-up | 0 | 0 | 16 |
Baseline characteristics
| Characteristic | Intervention | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 78 Participants | 57 Participants | 135 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 7 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 45 Participants | 40 Participants | 85 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown/Did Not Report | 22 Participants | 13 Participants | 35 Participants |
| Race/Ethnicity, Customized Race African American/Black | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Unknown/Not Reported | 11 Participants | 5 Participants | 16 Participants |
| Race/Ethnicity, Customized Race White | 60 Participants | 45 Participants | 105 Participants |
| Region of Enrollment Canada | 21 participants | 17 participants | 38 participants |
| Region of Enrollment United States | 50 participants | 38 participants | 88 participants |
| Sex: Female, Male Female | 21 Participants | 22 Participants | 43 Participants |
| Sex: Female, Male Male | 57 Participants | 35 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 54 | 0 / 99 |
| other Total, other adverse events | 22 / 69 | 24 / 54 | 26 / 99 |
| serious Total, serious adverse events | 0 / 69 | 0 / 54 | 0 / 99 |
Outcome results
Primary
CASI-5 Parent-rated Composite Score
Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5). The CASI-5 is based on the DSM-5 symptom criteria. The subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict that will be combined into a total composite score; range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome.
Time frame: Baseline and week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | CASI-5 Parent-rated Composite Score | Baseline | 1.49 score on a scale | Standard Error 0.08 |
| Intervention | CASI-5 Parent-rated Composite Score | Week 8 | 1.18 score on a scale | Standard Error 0.08 |
| Placebo | CASI-5 Parent-rated Composite Score | Baseline | 1.52 score on a scale | Standard Error 0.08 |
| Placebo | CASI-5 Parent-rated Composite Score | Week 8 | 1.23 score on a scale | Standard Error 0.08 |
Primary
Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2)
Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.
Time frame: Week 8
Population: Participants considered in the ITT analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2) | 38 Participants |
| Placebo | Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2) | 10 Participants |
Secondary
Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Albumin | 4.34 g/dL | Standard Error 0.17 |
| Intervention | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Total protein | 7.15 g/dL | Standard Error 0.63 |
| Intervention | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Hemoglobin | 12.99 g/dL | Standard Error 0.17 |
| Intervention | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Mean cell Hgb concentration | 33.82 g/dL | Standard Error 0.13 |
| Placebo | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Total protein | 8.45 g/dL | Standard Error 0.65 |
| Placebo | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Hemoglobin | 12.96 g/dL | Standard Error 0.17 |
| Placebo | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Mean cell Hgb concentration | 33.59 g/dL | Standard Error 0.13 |
| Placebo | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Albumin | 4.34 g/dL | Standard Error 0.17 |
| Placebo (Baseline) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Hemoglobin | 12.99 g/dL | Standard Error 0.18 |
| Placebo (Baseline) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Total protein | 7.07 g/dL | Standard Error 0.73 |
| Placebo (Baseline) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Mean cell Hgb concentration | 33.75 g/dL | Standard Error 0.15 |
| Placebo (Baseline) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Albumin | 4.29 g/dL | Standard Error 0.17 |
| Placebo (Week 8) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Mean cell Hgb concentration | 33.47 g/dL | Standard Error 0.15 |
| Placebo (Week 8) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Total protein | 7.06 g/dL | Standard Error 0.76 |
| Placebo (Week 8) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Albumin | 4.28 g/dL | Standard Error 0.17 |
| Placebo (Week 8) | Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL | Hemoglobin | 12.91 g/dL | Standard Error 0.18 |
Secondary
AST, ALT, Alkaline in U/L
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | AST, ALT, Alkaline in U/L | AST | 23.58 U/L | Standard Error 1.26 |
| Intervention | AST, ALT, Alkaline in U/L | Alkaline phosphatase | 255 U/L | Standard Error 8.1 |
| Intervention | AST, ALT, Alkaline in U/L | ALT | 18.67 U/L | Standard Error 3.25 |
| Placebo | AST, ALT, Alkaline in U/L | AST | 27.28 U/L | Standard Error 1.28 |
| Placebo | AST, ALT, Alkaline in U/L | Alkaline phosphatase | 241.33 U/L | Standard Error 8.15 |
| Placebo | AST, ALT, Alkaline in U/L | ALT | 26.00 U/L | Standard Error 3.27 |
| Placebo (Baseline) | AST, ALT, Alkaline in U/L | ALT | 20.40 U/L | Standard Error 3.37 |
| Placebo (Baseline) | AST, ALT, Alkaline in U/L | AST | 25.72 U/L | Standard Error 1.42 |
| Placebo (Baseline) | AST, ALT, Alkaline in U/L | Alkaline phosphatase | 252.21 U/L | Standard Error 9.29 |
| Placebo (Week 8) | AST, ALT, Alkaline in U/L | AST | 22.79 U/L | Standard Error 1.46 |
| Placebo (Week 8) | AST, ALT, Alkaline in U/L | Alkaline phosphatase | 257.93 U/L | Standard Error 9.41 |
| Placebo (Week 8) | AST, ALT, Alkaline in U/L | ALT | 18.09 U/L | Standard Error 3.41 |
Secondary
Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Glucose | 82.15 mg/dL | Standard Error 2.36 |
| Intervention | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Blood urea nitrogen (BUN) | 12.48 mg/dL | Standard Error 0.41 |
| Intervention | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Bilirubin total | 0.47 mg/dL | Standard Error 0.03 |
| Intervention | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Creatinine | 0.46 mg/dL | Standard Error 0.01 |
| Intervention | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Calcium | 9.47 mg/dL | Standard Error 0.2 |
| Placebo | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Creatinine | 0.49 mg/dL | Standard Error 0.01 |
| Placebo | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Glucose | 83.03 mg/dL | Standard Error 2.39 |
| Placebo | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Bilirubin total | 0.45 mg/dL | Standard Error 0.03 |
| Placebo | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Blood urea nitrogen (BUN) | 13.17 mg/dL | Standard Error 0.42 |
| Placebo | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Calcium | 9.49 mg/dL | Standard Error 0.2 |
| Placebo (Baseline) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Creatinine | 0.46 mg/dL | Standard Error 0.01 |
| Placebo (Baseline) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Calcium | 9.47 mg/dL | Standard Error 0.2 |
| Placebo (Baseline) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Blood urea nitrogen (BUN) | 12.56 mg/dL | Standard Error 0.46 |
| Placebo (Baseline) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Glucose | 79.45 mg/dL | Standard Error 2.44 |
| Placebo (Baseline) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Bilirubin total | 0.49 mg/dL | Standard Error 0.03 |
| Placebo (Week 8) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Glucose | 80.0 mg/dL | Standard Error 2.46 |
| Placebo (Week 8) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Blood urea nitrogen (BUN) | 12.13 mg/dL | Standard Error 0.48 |
| Placebo (Week 8) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Calcium | 9.40 mg/dL | Standard Error 0.2 |
| Placebo (Week 8) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Creatinine | 0.46 mg/dL | Standard Error 0.01 |
| Placebo (Week 8) | Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL | Bilirubin total | 0.46 mg/dL | Standard Error 0.03 |
Secondary
CASI-5 Parent Report
Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5) subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict. The CASI-5 is based on the DSM-5 symptom criteria. Item range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. The subscales for ADHD, ODD, and DMD will be composite scores.
Time frame: Week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | CASI-5 Parent Report | Week 12 | 1.14 score on a scale | Standard Error 0.04 |
| Intervention | CASI-5 Parent Report | Week 16 | 0.99 score on a scale | Standard Error 0.05 |
Secondary
Clinical Global Impression (CGI)
Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Clinical Global Impression (CGI) | 103 Participants |
Secondary
Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Hematocrit | 38.40 percent | Standard Error 0.52 |
| Intervention | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | RBC distribution | 25.03 percent | Standard Error 8.76 |
| Intervention | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Immature grans | 0.20 percent | Standard Error 0.02 |
| Intervention | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Lymphocyte | 43.63 percent | Standard Error 1.65 |
| Intervention | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Monocyte | 8.03 percent | Standard Error 0.34 |
| Intervention | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Eosinophil | 3.82 percent | Standard Error 0.63 |
| Placebo | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Eosinophil | 4.03 percent | Standard Error 0.64 |
| Placebo | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Lymphocyte | 43.53 percent | Standard Error 1.66 |
| Placebo | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Hematocrit | 38.60 percent | Standard Error 0.52 |
| Placebo | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Immature grans | 0.18 percent | Standard Error 0.02 |
| Placebo | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | RBC distribution | 25.17 percent | Standard Error 8.76 |
| Placebo | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Monocyte | 8.29 percent | Standard Error 0.34 |
| Placebo (Baseline) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | RBC distribution | 25.29 percent | Standard Error 8.76 |
| Placebo (Baseline) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Immature grans | 0.24 percent | Standard Error 0.02 |
| Placebo (Baseline) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Lymphocyte | 40.25 percent | Standard Error 1.8 |
| Placebo (Baseline) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Eosinophil | 6.49 percent | Standard Error 0.73 |
| Placebo (Baseline) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Monocyte | 7.78 percent | Standard Error 0.38 |
| Placebo (Baseline) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Hematocrit | 38.50 percent | Standard Error 0.55 |
| Placebo (Week 8) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Monocyte | 8.35 percent | Standard Error 0.38 |
| Placebo (Week 8) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Eosinophil | 5.71 percent | Standard Error 0.75 |
| Placebo (Week 8) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | RBC distribution | 25.02 percent | Standard Error 8.76 |
| Placebo (Week 8) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Lymphocyte | 40.65 percent | Standard Error 1.84 |
| Placebo (Week 8) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Hematocrit | 38.60 percent | Standard Error 0.55 |
| Placebo (Week 8) | Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent | Immature grans | 0.19 percent | Standard Error 0.03 |
Secondary
Iron in ug/dL
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Iron in ug/dL | 99.1 ug/dL | Standard Error 4.65 |
| Placebo | Iron in ug/dL | 90.7 ug/dL | Standard Error 4.69 |
| Placebo (Baseline) | Iron in ug/dL | 100.5 ug/dL | Standard Error 5.35 |
| Placebo (Week 8) | Iron in ug/dL | 95.5 ug/dL | Standard Error 5.49 |
Secondary
Mean Cell Volume in fL
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Mean Cell Volume in fL | 82.70 fL | Standard Error 0.44 |
| Placebo | Mean Cell Volume in fL | 83.00 fL | Standard Error 0.45 |
| Placebo (Baseline) | Mean Cell Volume in fL | 83.74 fL | Standard Error 0.49 |
| Placebo (Week 8) | Mean Cell Volume in fL | 83.85 fL | Standard Error 0.5 |
Secondary
RBC Count in Cells/mcL
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | RBC Count in Cells/mcL | 4,650,000 cells/mcL | Standard Error 0.08 |
| Placebo | RBC Count in Cells/mcL | 4,650,000 cells/mcL | Standard Error 0.08 |
| Placebo (Baseline) | RBC Count in Cells/mcL | 4,600,000 cells/mcL | Standard Error 0.08 |
| Placebo (Week 8) | RBC Count in Cells/mcL | 4,600,000 cells/mcL | Standard Error 0.09 |
Secondary
Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Carbon dioxide | 25.62 mmol/L | Standard Error 0.21 |
| Intervention | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Potassium | 4.1 mmol/L | Standard Error 0.1 |
| Intervention | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Anion gap | 10.30 mmol/L | Standard Error 2.83 |
| Intervention | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Chloride | 105.07 mmol/L | Standard Error 0.96 |
| Intervention | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Sodium | 139.13 mmol/L | Standard Error 0.34 |
| Placebo | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Chloride | 104.81 mmol/L | Standard Error 0.97 |
| Placebo | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Carbon dioxide | 25.64 mmol/L | Standard Error 0.22 |
| Placebo | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Anion gap | 10.64 mmol/L | Standard Error 2.83 |
| Placebo | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Potassium | 4.06 mmol/L | Standard Error 0.1 |
| Placebo | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Sodium | 139.16 mmol/L | Standard Error 0.34 |
| Placebo (Baseline) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Chloride | 104.88 mmol/L | Standard Error 0.97 |
| Placebo (Baseline) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Sodium | 139.28 mmol/L | Standard Error 0.36 |
| Placebo (Baseline) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Potassium | 4.09 mmol/L | Standard Error 0.1 |
| Placebo (Baseline) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Carbon dioxide | 25.97 mmol/L | Standard Error 0.24 |
| Placebo (Baseline) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Anion gap | 10.31 mmol/L | Standard Error 2.83 |
| Placebo (Week 8) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Carbon dioxide | 25.86 mmol/L | Standard Error 0.25 |
| Placebo (Week 8) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Potassium | 4.0 mmol/L | Standard Error 0.1 |
| Placebo (Week 8) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Sodium | 139.42 mmol/L | Standard Error 0.37 |
| Placebo (Week 8) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Chloride | 105.28 mmol/L | Standard Error 0.98 |
| Placebo (Week 8) | Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L | Anion gap | 10.15 mmol/L | Standard Error 2.84 |
Secondary
WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL
Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
Time frame: Baseline and Week 8
Population: Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | WBC count | 5,710 cells/mcL | Standard Error 0.22 |
| Intervention | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute monocyte | 460 cells/mcL | Standard Error 0.02 |
| Intervention | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute eosinophil | 210 cells/mcL | Standard Error 0.04 |
| Intervention | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Platelet count | 289,970 cells/mcL | Standard Error 7.54 |
| Placebo | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Platelet count | 289,320 cells/mcL | Standard Error 7.57 |
| Placebo | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute eosinophil | 230 cells/mcL | Standard Error 0.04 |
| Placebo | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute monocyte | 470 cells/mcL | Standard Error 0.02 |
| Placebo | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | WBC count | 5,730 cells/mcL | Standard Error 0.23 |
| Placebo (Baseline) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute eosinophil | 390 cells/mcL | Standard Error 0.04 |
| Placebo (Baseline) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Platelet count | 290,160 cells/mcL | Standard Error 8.62 |
| Placebo (Baseline) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute monocyte | 460 cells/mcL | Standard Error 0.02 |
| Placebo (Baseline) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | WBC count | 6,080 cells/mcL | Standard Error 0.25 |
| Placebo (Week 8) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Platelet count | 295,900 cells/mcL | Standard Error 8.75 |
| Placebo (Week 8) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | WBC count | 5,990 cells/mcL | Standard Error 0.26 |
| Placebo (Week 8) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute monocyte | 480 cells/mcL | Standard Error 0.02 |
| Placebo (Week 8) | WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL | Absolute eosinophil | 340 cells/mcL | Standard Error 0.05 |