Attention-deficit/Hyperactivity Disorder Translational Center for Identifying Biomarkers

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to identify genetic, brain morphologic, and environmental biomarkers that contribute to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD).

Detailed Description
-----------------
The investigators planned to recruit ADHD and healthy controls from the age of 6 to 17. Genetic data including dopamine, norepinephrine, serotonin, neurotropic factors, glutamate-related genes will be genotyped. Environmental disruptors including phthalate and cotinine will be analyzed. Brain MRI data including T1, diffusion tensor imaging (DTI), resting state functional MRI (rsfMRI) will be obtained. Neuropsychological tests including continuous performance test, Stroop test, Children's color trail test, Wisconsin card sorting test will be conducted. The investigators plan to identify biomarkers of ADHD using an integrative approach of genetic, environmental, neuroimaging and clinical data.

Official Title
-----------------
Comprehensive Pathophysiological Study Based on the Core Neurocognitive Deficits and Development of Biological Markers of Treatment Response in Attention Deficit Hyperactivity Disorder

Conditions
-----------------
Attention-deficit/Hyperactivity Disorder

Intervention / Treatment
-----------------
* Drug: methylphenidate
* Drug: atomoxetine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A diagnosis of attention-deficit/hyperactivity disorder confirmed using the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version- Korean Version (K-SADS-PL-K). IQ over 70 Exclusion Criteria: Intelligence quotient (IQ) < 70 A hereditary genetic disorder A current/past history of brain trauma, organic brain disorder, seizure, or any neurological disorder Autism spectrum disorder, communication disorder, or learning disorder Schizophrenia or any other childhood-onset psychotic disorder Major depressive disorder or bipolar disorder Tourette's syndrome or chronic motor/vocal tic disorder obsessive-compulsive disorder A history of methylphenidate treatment lasting more than 1 year or received within the previous 4 weeks

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate<br>ADHD patients with methylphenidate administration Generic names include concerta, metadata and penid. The initial dosage was fixed for 2 weeks and then adjusted according to the clinician's judgement. The patients visited the hospital at week 2,4,6,8,16,24, 9months, 12,15,18,21,24 months. | Drug: methylphenidate<br>* The patients received a fixed dose of medication for 2 weeks. The dose was increased according to the clinician's judgment. The patients came to the hospital at week 2,4,6,8,16,24wks, 9, 12,15,18,21,24 months<br>* Other names: concerta, metadate, penid;|
| Experimental: Atomoxetine<br>ADHD patients with atomoxetine administration Generic names include strattera. The initial dosage was fixed for 2 weeks and then adjusted according to the clinician's judgement. The patients visited the hospital at week 2,4,6,8,16,24, 9months, 12,15,18,21,24 months. | Drug: atomoxetine<br>* The patients received a fixed dose of medication for 2 weeks. The dose was increased according to the clinician's judgment. The patients came to the hospital at week 2,4,6,8,16,24wks, 9, 12,15,18,21,24 months<br>* Other names: strattera;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response measured by decrease in ADHD-RS scale | Changes in the Parent rated ADHD-Rating Scale - IV (ADHD-RS), which is an 18 item scale, with 9 items assessing inattention and 9 items assessing hyperactivity/impulsivity. It is the most widely used scale to measure symptom severity of attention-deficit/hyperactivity disorder. | 6 months | 
| Treatment response measured by CGI-I score | The Clinical Global Impression - Improvement (CGI-I) scale is a clinician rated scale used to measure improvement in symptoms. It ranges from 1 to 7, with 1 meaning very much improved, and 7 meaning very much worse. | 6 months | 
| Treatment response measured by changes in CPT score | The continuous performance test (CPT) is an objective measurement of ADHD symptom severity. It is a computerized test and the results are presented in 4 variables : omission errors, commission errors, response time, response time variability. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response measured by decrease in ADHD-RS scale | The ADHD-RS scale is described in primary outcome measures. | 1 year | 
| Side effects measured using the side effect rating scale (SRS) | The side effect rating scale (SRS) is a parent rated scale, measuring side effects of multiple domains in the previous 2 week period. | 1 year | 
| Treatment response measured by CGI-I score | The CGI-I scale is described in primary outcome measures. | 1 year |