Attention-deficit/Hyperactivity Disorder Translational Center for Identifying Biomarkers

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

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).

Study Overview

• Status: Unknown
• Conditions: Attention-deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: methylphenidate; Drug: atomoxetine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Children's Hospital
    • Contact: Johanna Kim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylphenidate; 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; 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; Other Names: concerta, metadate, penid
Experimental: Atomoxetine; 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; 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; 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

Collaborators and Investigators

• Sponsor: Seoul National University Childrens Hospital
• Investigators: Principal Investigator: Boong-nyun Kim, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: November 29, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Adrenergic Uptake Inhibitors; Methylphenidate; Atomoxetine Hydrochloride
• Other Study ID Numbers: 0720151002