The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With ADHD: A Lipidomic Study

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

The Neuroprotective Effects of Methylphenidate and Atomoxetine in Children With Attention Deficit Hyperactivity Disorder: A Lipidomic Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03936491
• Other study ID #: 201812200MINA
• Status: Completed
• Phase: N/A
• Start date: August 1, 2019
• Est. completion date: January 25, 2021

Study information

• Verified date: April 2024
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. To identify the difference in the lipidomic profiles between ADHD and controls;

2. To examine the effects of methylphenidate and atomoxetine on the lipidomic profiles in ADHD, and the relationship between medication-related changes in the lipidomic profiles and medication-related improvements in the behavioral symptoms and neuropsychological functions;

3. To map medication-related lipidomic biomolecules to their respective metabolic pathways to identify the underlying mechanisms of neuroprotective effects of methylphenidate and atomoxetine.

Description:

Background: Although the efficacy of methylphenidate and atomoxetine in ADHD is well documented in clinical trials, more studies are needed to clarify the neuroprotective effects of these two medications. Lipids exert important neuroprotective effects for optimal brain development and functioning. Previous studies have demonstrated the significant connection between lipid dysregulation and the occurrence of ADHD. In addition, lipid dysregulation is closely related to the abnormal neural activity in individuals with ADHD. In this 3-year prospective project, we will perform a lipidomic analysis of blood before and after treatment with methylphenidate or atomoxetine, in order to identify the biological connections between the neuroprotective effects of medications and pathways of lipid metabolism in children with ADHD.

Subjects and Methods: 70 drug-naïve patients with ADHD, aged 6-18, and 35 matched typically developing controls will be recruited in this project. We will randomly assign the 70 ADHD patients to two groups, 35 in the methylphenidate group and 35 in the atomoxetine group. Within the 12-week treatment period, we will use ADHDRS-IV, SNAP-IV, CBCL, YSR, CGI-ADHD-S, CGI-ADHD-I, SAICA, and Family APGAR-C to assess the improvement in the behavioral symptoms, and CPT and CANTAB to assess the improvement in the neuropsychological functioning. The blood sample will be collected, and we will use mass spectrometry to assess the medication-related change in lipidomic profiles.

Anticipated Results: Using a prospective design, we anticipate that this study will delineate the effects of methylphenidate and atomoxetine on the lipidomic profiles in patients with ADHD. Furthermore, we will conduct pathway analysis to obtain crucial insight to the lipidomic regulation in neurophysiology of children with ADHD. We expect that the findings will increase our understanding of the neuroprotective effects of methylphenidate and atomoxetine in patients with ADHD, and identify the psychopharmacological mechanism of medication effects in ADHD via the pathways of lipid metabolism and regulation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: January 25, 2021
• Est. primary completion date: January 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

Subjects will be recruited in the present project if they meet the following inclusion criteria:

1. Children or adolescents, between 6 and 18 years of age, must have ADHD based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental disorders, 5th edition.

2. Their scores of Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) is greater than 4 at baseline.

3. They have to be medication-naïve. They never receive any medication for the treatment of ADHD.

4. They and their parents must understand sufficiently to communicate properly with the investigators.

5. They must have a Full-Scale Intelligence Quotient (FIQ) score greater than 80.

6. They must keep regular clinic visits and all required tests, including collection of blood sample and neuropsychological testing.

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• Methylphenidate
Methylphenidate is a central nervous system stimulant used for the therapy of attention deficit disorder and narcolepsy.
• Atomoxetine
Atomoxetine is a medication used to treat attention deficit hyperactivity disorder (ADHD).[6] Use is only recommended in those who are at least six years old.[6] It is taken by mouth.[6]

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ADHD Rating Scale-IV-Parent version: Investigator-Administered and Scored (ADHDRS-IV)	The first efficacy measure is the ADHDRS-IV, which is a scale composed of 18 items. The investigator will conduct a semi-structured interview with the parent to evaluate the severity of ADHD symptoms in the past week. ADHDRS-IV is a valid and reliable tool to assess the severity of ADHD symptoms, which has been widely used in pharmacological studies of ADHD in Taiwanese populations. ADHDRS-IV will be administered from visit 1 through visit 5 (baseline-week 12).	12 weeks
Secondary	Swanson, Nolan, and Pelham IV scale (SNAP-IV), Parent Form and Teacher Form	The SNAP-IV is composed of the ADHD symptoms for the inattention (Items 1 to 9), the hyperactivity/impulsivity (Items 10 to 18), and the oppositional symptoms (Items 19 to 26). SNAP-IV has been proved to be a valid and reliable tool to evaluate the severity of ADHD symptoms. The Chinese SNAP-IV has been used widely in the pharmacological studies on ADHD in Taiwanese populations. SNAP-IV will be administered from visit 1 through visit 5 (baseline-week 12).	12 weeks