Metabolic Mechanisms of the Electrophysiological Biomarkers for Response to Methylphenidate Treatment in Children With ADHD

Metabolomics Clinical Trial

Official title:

Exploration of the Metabolic Mechanisms of the Electrophysiological Biomarkers for Response to Methylphenidate Treatment in Children With Attention-Deficit/Hyperactivity Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06073470
• Other study ID #: 202204054RINC
• Status: Recruiting
• Start date: January 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: September 2023
• Source: National Taiwan University Hospital
• Contact: Chi-Yung Shang, MD, PhD
• Phone: +886-2-23123456
• Email: cyshang[@]ntu.edu.tw
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To explore the relationship of treatment-related changes in electrophysiology and those in metabolomics for identification of the underlying metabolic mechanisms for the electrophysiological effects of methylphenidate in children with ADHD.

Description:

Although the efficacy of methylphenidate in reducing the core symptoms of attentiondeficit/ hyperactivity disorder (ADHD) is well documented in clinical trials, no definite biomarker has been identified to differentiate responders from non-responders to methylphenidate treatment for children with ADHD. In addition, the neural and metabolic mechanisms underlying the therapeutic effects of methylphenidate remain to be elucidated. In this 4-year prospective project, the investigators will explore the effects of 12-week treatment with methylphenidate on the electrophysiology and metabolomics of children with ADHD to identify the biomarkers for predicting the clinical response to methylphenidate. In addition, the investigators will explore the metabolic mechanisms through which methylphenidate treatment may modulate the abnormality in the electrophysiology of children with ADHD. Specific Aims: 1. To examine the differences in electrophysiology and metabolomics between children with ADHD and neurotypical controls. 2. To examine the differences in the change of electrophysiology and metabolomics after 12-week treatment with methylphenidate between responders and non-responders in children with ADHD. 3. To explore the relationship of treatment-related changes in electrophysiology and those in metabolomics for identification of the underlying metabolic mechanisms for the electrophysiological effects of methylphenidate in children with ADHD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

1. Patients with ADHD

1. Inclusion Criteria

• Patients, aged 6 to 18 years, meet the DSM-5 diagnostic criteria for ADHD.
• At baseline, patients have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score greater than 4.
• Patients have a Full IQ (FIQ) score greater than 80.

2. Exclusion Criteria

• Patients have a major psychiatric disorder, such as autism spectrum disorder, schizophrenia, affective disorders, or substance use disorders.
• Patients have a major disorder of central nervous system, such as epilepsy.
• Patients have a major systemic disease, such as diabetes mellitus or cardiovascular diseases.
• Patients have ever received any medication to treat the clinical symptoms of ADHD.

2. Neurotypical participants:

1. Inclusion Criteria

• aged 6 to 18 years
• All of the neurotypical participants have no psychiatric disorder in lifetime according to the diagnostic criteria of DSM-5.

2. Exclusion Criteria

• participants have any disorder of central nervous system or major systemic disease
• participants have ever taken any psychotropic drug, or who have FIQ scores less than 80, will be excluded from the present study.

Related Conditions & MeSH terms

• Metabolomics
• Methylphenidate

Intervention

Drug:
• methylphenidate
The patients with ADHD will receive 12-week treatment with methylphenidate.

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	Diagnostic interview	We will interview all the participants and their parents to examine whether the participants have any psychiatric disorder by employing the Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia (K-SADS-E).	1 hour
Primary	ADHD symptoms	Subjects will be interviewed by ADHD rating scale , which consists of 18 items to measure the symptomatology of ADHD . Each question in this questionnaire is scaled from 0 to 3. The higher the total score, the more severe the symptoms.	15 minutes
Secondary	Questionnaire	Cases and parents assisted in filling out the Achenbach child behavior check list (CBCL).Each question in this questionnaire is scaled from 1 to 3. The higher the total score, the more severe the emotional and behavioral distress.	5minutes
Secondary	Questionnaire	Cases and parents assisted in filling out the Swanson, Nolan, and Pelham Rating Scale Fourth Edition (SNAP-IV).Each question in this questionnaire is scaled from 0 to 3. The higher the total score, the more severe the symptoms.	5minutes
Secondary	Questionnaire	Cases and parents assisted in filling out the Family APGAR questionnaire.Each question in this questionnaire is scaled from 0 to 2. The higher the total score, the better the family function.	5minutes
Secondary	Questionnaire	Cases and parents assisted in filling out the Social Adjustment Inventory for Children and Adolescents questionnaire (SAICA).The scale for each question in this questionnaire ranges from 1 to 4. The higher the total score, the worse the social adaptation status.	5minutes
Secondary	Questionnaire	Cases and parents assisted in filling out the Behavior Rating Inventory of Executive Function questionnaire(BRIEF).Each question in this questionnaire is scaled from 1 to 3. The higher the total score, the lower the executive function status.	5minutes
Secondary	Neurobiological assessments	Resting state EEG will be recorded in NTUH ERP lab.The EEG will be processed for functional connectivity indices between regions are calculated using the magnitude squared coherence (Coh) in the delta(delta)/theta(theta)/alpha(alpha)/beta(beta) frequency bands and the nonlinear index (L) of generalized synchronization.	10minutes
Secondary	Neurobiological assessments	Resting state EEG will be recorded in NTUH ERP lab. Phase transfer entropy (PTE) will be used to construct the effective connectivity. The topological properties of networks and flow gain are measured separately in four bands (delta, theta, alpha, and beta).	10minutes
Secondary	Neurobiological assessments	Resting state EEG will be recorded in NTUH ERP lab. We will perform Fast Fourier Transform using the pwelch algorithm, with a 128 sample triangular window, to obtain time-frequency domain measures. Mean spectral estimates in various power bands are computed. As a measure of intraindividual variability in neural activity, the standard deviation of the power in each 2-second trial is calculated for each band for each participant.	10minutes
Secondary	Neurobiological assessments	auditory MMN/P3a (task-free ERP) will be recorded in NTUH ERP .	30minutes
Secondary	Neurobiological assessments	dichotic continuous performance task(DCPT, task-related ERP modified from Conner's CATA) will be recorded in NTUH ERP lab.	20minutes
Secondary	liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry	Whole blood samples will be collected after 8 hours of fasting at baseline and week 12 for neurotypical controls and for patients with ADHD. The investigators will employ both liquid chromatography coupled to mass spectrometry (LC/MS) and gas chromatography coupled to mass spectrometry (GC/MS) to conduct the experiments of metabolomic profiling of the serum at the Metabolomics Core Laboratory, National Taiwan University.	5 minutes
Secondary	Neuropsychological testing	Subjects will be assessed by the WISC-V(Wechsler Intelligence Scale for Children),WISC-V scores between 90 and 109 represent moderate general intelligence, and higher scores represent relatively better cognitive function.	1.5 hours