Identification of Neuropsychological, Genetic and Neuroimaging Markers and Treatment Response Predictors of ADHD

Neuropsychological, Genetic and Neuroimaging Markers and Treatment Response Predictors of Attention-Deficit/Hyperactivity Disorder (ADHD)

The objective of this study is to identification of neuropsychological, genetic and neuroimaging markers and treatment response predictors of attention-deficit/hyperactivity disorder (ADHD). Participants who take the standardized pharmacotherapy (methylphenidate or atomoxetine) for ADHD will be observed for 52 weeks. They will do several neuropsychological, neuroimaging and genetic tests at visit 1~6.

Study Overview

• Status: Unknown
• Conditions: Attention Deficit Disorder With Hyperactivity
• Intervention / Treatment: Drug: Methylphenidate (MPH); Drug: Atomoxetine

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: Hyo-Won Kim, MD, PhD; Phone Number: 82-3010-3414; Email: shingubi@amc.seoul.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Total 600 children and adolescents will be enrolled in this study. 500 patients in psychiatric outpatient will be enrolled. 100 persons of healthy volunteers will be recruited via advertisements.

Description

Inclusion Criteria:

1. aged between 6 and 12 years
2. met the Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) diagnostic criteria for ADHD and needed pharmacotherapy.
3. Informed consent

Exclusion Criteria:

1. presence of intellectual disability or learning disorder
2. past and/or current history of bipolar disorder or psychosis or substance use disorder
3. past and/or current history of pervasive developmental disorder, organic mental disorder or other neurological disorder
4. presence of sever suicidal ideation
5. presence of tic disorder or obsessive-compulsive disorder whose symptoms needed pharmacotherapy
6. presence of family history with Tourette's Syndrome
7. took medication with methylphenidate or atomoxetine with last 6 month (or more than 3 month)
8. presence of severe medical condition (ex. cardiologic, liver, kidney, pulmonary, glaucoma)
9. took alpha 2 adrenergic receptor agonist, antidepressant, antipsychotics, benzodiazepine, modafinil, antiepileptic drug or dietary supplement that have a influence on Central Nervous System (CNS).
10. presence of possibility with pregnancy

11. especially for neuroimaging,

    1. uncooperative with claustrophobia or body movement
    2. metal material inside body that can't take off

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ADHD group; Children and adolescents who met the Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) diagnostic criteria for ADHD and needed pharmacotherapy. Subjects will be taking Methylphenidate or Atomoxetine for 52 weeks.	Drug: Methylphenidate (MPH); Subjects of ADHD group will be taking methylphenidate or atomoxetine for 52 weeks.; Other Names: Concerta®; Metadate CD®; Medikinet Retard®; Drug: Atomoxetine; Subjects of ADHD group will be taking methylphenidate or atomoxetine for 52 weeks.; Other Names: Straterra®
Normal control group; Children and adolescents will be recruited by advertisement, and will be assigned to normal group if they do not meet the Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) diagnostic criteria for ADHD .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wide genome analysis regarding genetic polymorphisms as predictors of treatment response in Attention-Deficit/Hyperactivity Disorder(ADHD).	Genome wide case-control association analysis will be operated with qualified phenotype and assigned intermittent phenotype.	visit 1 (-week 8)
Neuroimaging analysis as predictors of treatment response in Attention-Deficit/Hyperactivity Disorder(ADHD).	Thickness of cortex, anatomical relation will be compared with 3 tesla MRI. In addition, brain circuit for delayed aversion, delayed frustration, time processing and resting state.	visit 1 (-week 8)
Drug effectiveness is assessed using ADHD rating scale, CGI -S (Clinical Global Impression - Severity scale) and CGI-I (Clinical Global Impression - Improvement scale).		visit 1 (-week 8)
Neuropsychological markers as the treatment response predictable factor of ADHD using a complex neuropsychological test consisting of SSRT, delayed aversion, delayed frustration, time processing, ATA	Using a complex neuropsychological test consisting of The stop-signal reaction time (SSRT) task, delayed aversion, delayed frustration, time processing, Advanced tets of Attention (ATA).	visit 1 (-week 8)
Comorbidity assessment using a composite measure consisting of K-PRC, C-SSRS, TCGI, and DCDQ	It is assessed using a composite measure consisting of Korean Personality Rating Scale for Children (K-PRC), Columbia Suicide Severity Rating Scale (C-SSRS), The Tic Severity Scale (TCGI), and The Developmental Coordination Disorder Questionnaire (DCDQ).	visit1 (-week 8)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in treatment response effectiveness of pharmacotherapy at week12	Drug effectiveness is assessed using ADHD rating scale, CGI -S (Clinical Global Impression - Severity scale) and CGI-I (Clinical Global Impression - Improvement scale).	visit 3 (week12)
Change from baseline in treatment response effectiveness of pharmacotherapy at week 24	Drug effectiveness is assessed using ADHD rating scale, CGI -S (Clinical Global Impression - Severity scale) and CGI-I (Clinical Global Impression - Improvement scale).	visit 4 (week 24)
Change from baseline in treatment response effectiveness of pharmacotherapy at week 36	Drug effectiveness is assessed using ADHD rating scale, CGI -S (Clinical Global Impression - Severity scale) and CGI-I (Clinical Global Impression - Improvement scale).	visit 5 (week 36)
Change from baseline in treatment response effectiveness of pharmacotherapy at week 52	Drug effectiveness is assessed using ADHD rating scale, CGI -S (Clinical Global Impression - Severity scale) and CGI-I (Clinical Global Impression - Improvement scale).	visit 6 (week 52)
Change from baseline in neuropsychological markers as the treatment response predictable factor of ADHD using a complex neuropsychological test consisting of SSRT, delayed aversion, delayed frustration, time processing, ATA at week 12	Using a complex neuropsychological test consisting of The stop-signal reaction time (SSRT) task, delayed aversion, delayed frustration, time processing, Advanced tets of Attention (ATA).	visit 3 (week 12)
Change from baseline in neuropsychological markers as the treatment response predictable factor of ADHD using a complex neuropsychological test consisting of SSRT, delayed aversion, delayed frustration, time processing, ATA at week 52	Using a complex neuropsychological test consisting of The stop-signal reaction time (SSRT) task, delayed aversion, delayed frustration, time processing, Advanced tets of Attention (ATA).	visit 6 (week 52)
Occurrence of comorbidity from baseline in assessment using a composite measure consisting of K-PRC, C-SSRS, TCGI, and DCDQ at week 12	It is assessed using a composite measure consisting of Korean Personality Rating Scale for Children (K-PRC), Columbia Suicide Severity Rating Scale (C-SSRS), The Tic Severity Scale (TCGI), and The Developmental Coordination Disorder Questionnaire (DCDQ).	visit 3 (week 12)
Occurrence of comorbidity from baseline in assessment using a composite measure consisting of K-PRC, C-SSRS, TCGI, and DCDQ at week 52	It is assessed using a composite measure consisting of Korean Personality Rating Scale for Children (K-PRC), Columbia Suicide Severity Rating Scale (C-SSRS), The Tic Severity Scale (TCGI), and The Developmental Coordination Disorder Questionnaire (DCDQ).	visit 6 (week 52)

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Hyo-Won Kim, Professor, Asan Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: April 20, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: neuroimaging; genetic markers; Neuropsychological; treatment response predictor
• 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: S2013-0373-0014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO