Identify Peripheral Biomarkers of Symptomatology, Neurocognitive Functions, and Medication Response in ADHD

Attention-deficit/Hyperactivity Disorder Clinical Trial

Official title: A Study to Identify the Peripheral Biomarkers of Symptomatology, Neurocognitive Functions, and Medication Response in Attention Deficit Hyperactivity Disorder

Status Recruiting

Clinical Trial Summary

Attention deficit hyperactivity disorder (ADHD), characterized by inattention, hyperactivity and impulsivity, is an early onset, highly heritable, clinically heterogeneous, long-term impairing disorder with tremendous impact on individuals, families, and societies. It affects 5-10% of school-aged children worldwide (7.5% in Taiwan) and 2-4% of adults. Although the efficacy of medications for ADHD is well demonstrated in clinical trials, substantial numbers of patients fail to remain on therapy, and there is tremendous variability in tolerability and treatment acceptance. It is of great interest to identify biomarkers relating to medication response in ADHD. However, the procedure for obtaining central markers such as PET scan is invasive and expensive. Previous studies have found that mRNA expression of neurochemical markers in circulating blood can reflect the neurochemical levels in the brain. Further studies to identify peripheral biomarkers related to medication response in ADHD are warranted.

Clinical Trial Description

Specific Aims:

1. to examine the relationship between peripheral mRNA expression levels of dopamine markers (DAT1, DRD1, DRD2, DRD3, DRD4, and DRD5) and symptomatology of ADHD;

2. to examine the relationship between peripheral mRNA expression levels of dopamine markers and neurocognitive endophenotypes of ADHD;

3. to identify the specific dopamine markers of methylphenidate effects on the symptomatology of ADHD;

4. to identify the specific dopamine markers of methylphenidate effects on the neurocognitive endophenotypes of ADHD.

Subjects and Methods: We will recruit 120 drug-naïve ADHD patients, aged 7-18 in this 3-year project. The patients will receive methylphenidate, and the medication response will be assessed regularly within 12-week treatment period (Week 0, 2, 4, 8, and 12). The primary efficacy measure is the ADHDRS and CGI-ADHD-S. The secondary measures include the SNAP-IV, CBCL, CGI-ADHD-I, SAICA, and Family APGAR. Neuropsychological testing, including WISC-III, CPT, and CANTAB, will be performed. The blood sample will be collected, and the mRNA expression levels of dopamine markers (DAT1, DRD1, DRD2, DRD3, DRD4, and DRD5) hypothesized to influence medication effects risks for ADHD will be analyzed.

Anticipated Results: Our study will identify peripheral dopamine biomarkers that can predict individual variability in symptomatology and neurocognitive functions following treatment with methylphenidate. The ability of peripheral biomarkers to predict response to methylphenidate administration can have important implications for personalizing the treatment for ADHD, allowing clinicians to predict which patients will receive greatest benefit from dopaminergic medications. The use of mRNA screening in dosing will provide a model for future drug development, in which outcome variability is assessed in subgroups of peripheral dopamine markers and not merely on the basis of treatment assignment. In addition, the findings of such approaches to identify the peripheral biomarkers on the drug response in this study should help us to extend our understanding of the pathophysiological mechanism of ADHD. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention-deficit/Hyperactivity Disorder
• Hyperkinesis

• NCT number: NCT02074228
• Study type: Interventional
• Source: National Taiwan University Hospital
• Contact: Chi-Yung Shang, Ph.D.
• Phone: +886-2-2312-3456
• Email: cyshang@ntu.edu.tw
• Status: Recruiting
• Phase: Phase 4
• Start date: August 2012
• Completion date: July 2015