Towards an Understanding of the Mechanism of Action of Methylphenidate in ADHD

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

Understanding the Mechanism of Action of Methylphenidate in ADHD: A Computational Psychiatry Approach

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05600881
• Other study ID #: MPH2022TCD
• Status: Not yet recruiting
• Start date: June 2023
• Est. completion date: September 2026

Study information

• Verified date: May 2023
• Source: University of Dublin, Trinity College
• Contact: Julia Paterson, BSc, BCompSci
• Phone: 0896164340
• Email: jpaterso[@]tcd.ie
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Approximately 1-in-20 children worldwide have Attention Deficit Hyperactivity Disorder (ADHD), a condition associated with disabling inattention, hyperactivity and impulsivity. These problems can manifest as poor inhibitory control (e.g., difficulty holding back impulsive actions) and atypical reward processing (e.g., failing to learn from adverse outcomes). Poorly treated ADHD is associated with negative academic and socioeconomic consequences.

This project aims to ultimately improve clinical management of children with ADHD. Methylphenidate, a stimulant medication, is used as the first-option pharmacological treatment for ADHD and often successfully reduces problem behaviour. Although Methylphenidate can be extremely effective, it does not work for every child. There is currently no 'objective' way (e.g., blood test or brain scan) to measure if a child is genuinely responding to Methylphenidate. Instead, clinicians must rely on reports from parents and teachers, an approach that is problematic and that often leads to delays in optimising ADHD treatment. The absence of a biological test to quantify Methylphenidate response is primarily because we do not understand exactly how Methylphenidate changes behaviours to produce the known beneficial effects. This lack of knowledge is despite the very common use of this medication.

This project will investigate the specific brain processes that are affected by Methylphenidate by recording brain activity and behaviour in children with ADHD (who have already been prescribed Methylphenidate as part of their clinical care) when they are on and off this medication. Brain activity will be recorded using two separate approaches, which are both non-invasive and routinely used in Trinity College Institute of Neuroscience: electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Brain activity data will be collected while children with ADHD are performing two computer-game like tasks. One task measures the child's ability to hold back impulsive actions (inhibition) and the other assesses how they learn from positive and negative outcomes (reward processing). The data from the two tasks, the EEG recording and the fMRI scan will be analysed using advanced computer-modelling approaches to determine exactly how Methylphenidate changes behaviour.

This project is important because if we can understand the brain mechanisms affected by Methylphenidate, we can ultimately develop a computerised measure that will allow clinicians to predict whether a child is going to respond to this treatment or not. Such a measure would allow clinicians to treat ADHD more effectively and would result in children with ADHD experiencing faster relief from symptoms.

Description:

This project will investigate the specific brain processes that are affected by Methylphenidate by recording brain activity and behaviour in children with ADHD (who have already been prescribed Methylphenidate as part of their clinical care) when they are on and off this medication.

This is a quantitative double-blind placebo-controlled study investigating the acute effects of methylphenidate on brain activity using two non-invasive methods, EEG and fMRI.

Brain activity will be recorded using two separate approaches, which are both non-invasive and routinely used in Trinity College Institute of Neuroscience: electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Brain activity data will be collected while children with ADHD are performing two computer-game like tasks. One task measures the child's ability to hold back impulsive actions (inhibition) and the other assesses how they learn from positive and negative outcomes (reward processing). The data from the two tasks, the EEG recording, and the fMRI scan will be analysed using advanced computer-modelling approaches to determine exactly how Methylphenidate changes behaviour.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 35
• Est. completion date: September 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 18 Years

Eligibility

Inclusion Criteria:

AFAB Clinical diagnosis of ADHD Must be able to swallow tablets Regular menstrual cycles Good response to medication

Exclusion Criteria:

Intellectual Disability Specific Learning Disabilities

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder

Intervention

Drug:
• Methylphenidate
Participants will take their regular medication or a placebo (vitamin C)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Dublin, Trinity College	St. James's Hospital, Ireland

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	EEG	during SST	2023-2026
Primary	MRI	structural, diffusion, functional	2023-2026
Secondary	Stop Signal Task	behavioural measures	2023-2026