Multimodal Brain Imaging of Methylphenidate in Children and Adolescents With ADHD

Multimodal Brain Imaging of the Neural Effects of Methylphenidate in Children and Adolescents With ADHD

The goal of this proposal is to develop brain imaging tools to measure the effects of methylphenidate in children and adolescents with attention deficit hyperactivity disorder (ADHD). Methylphenidate is an FDA-approved treatment for ADHD. Specifically, the investigators will correlate brain activity during cognitive tasks and brain chemistry with cognitive performance. These measures could help the investigators understand how current ADHD medications work and then could be used to develop novel drugs to treat ADHD in children and adolescents.

Study Overview

• Status: Withdrawn
• Conditions: ADHD
• Intervention / Treatment: Drug: Placebo; Drug: Methylphenidate

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 6 to 18 years
• Diagnosis of ADHD
• A score of at least 3 (mildly ill) on the clinician administered Clinical Global Impressions-Severity (CGI-S)

Exclusion Criteria:

• Currently taking stimulant medications (within one week of first study visit). Patients will not be asked to discontinue any treatments for the purpose of this research study. Subjects will include treatment naïve patients and patients who were previously treated with stimulant medications, but are not currently treated, and meet study criteria.
• Having an adverse reaction to methylphenidate, or other stimulant medication
• Current psychiatric disorder, including bipolar I or II disorder, major depressive, disorder, obsessive-compulsive disorder, autism spectrum disorder, Tourette syndrome, or history of psychosis
• Patient is at risk for clinically significant deterioration due to study protocol, as assessed by primary medical investigator (Dr. Grant)
• Confirmed genetic disorder with cognitive and/or behavioral disturbances
• Active, unstable medical illness that may interfere with cognition or compromises safety of the patient
• History of head trauma with loss of consciousness or any evidence of functional impairment due to, and persisting after, head trauma
• Neurological disorder, mental retardation, intellectual or disability, or other non-ADHD cause of cognitive impairment
• Pregnant or breast-feeding women
• Having a contraindication to MRI, including a pacemaker, defibrillator or other medical implant, other metal objects, or claustrophobia, or for having braces or other metal in the head region (likely to create an artifact on the MRI scans).
• Currently smoking or using controlled or illicit substances, including alcohol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo; oral placebo
Experimental: Methylphenidate - low dose; 5 mg of methylphenidate	Drug: Methylphenidate; Single oral dose of methylphenidate (5mg or 10 mg); Other Names: Ritalin
Experimental: Methylphenidate - high dose; 10 mg of methylphenidate	Drug: Methylphenidate; Single oral dose of methylphenidate (5mg or 10 mg); Other Names: Ritalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD signal during response inhibition	Blood oxygenation level dependent (BOLD) signal (brain activity during functional magnetic resonance imaging (fMRI), arbitrary units) in the anterior cingulate cortex during response inhibition.	Approximately 90 minutes after dose
BOLD signal during working memory	BOLD signal (brain activity during fMRI, arbitrary units) in the frontal cortex during working memory	Approximately 90 minutes after dose
Glutamate level in the anterior cingulate cortex	Glutamate level (measured by magnetic resonance spectroscopy (MRS), institutional units) in the anterior cingulate cortex (ACC).	Approximately 2 hours after dose
Glutamate level in the dorsolateral prefrontal cortex	Glutamate level (measured by MRS, institutional units) in the dorsolateral prefrontal cortex	Approximately 2 hours after dose
Cognitive performance as assessed by the Flanker performance task	NIH Toolbox Cognitive Battery Flanker task, score range 0 to 20, higher score is better performance	Approximately 3 hours after dose
Working memory performance	NIH Toolbox Cognitive Battery working memory task (list sorting), score range 0 to 26, higher score is better performance	Approximately 3 hours after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD as assessed by the Connors 3	Connors 3rd edition ADHD assessment, lower score means less symptoms, typical scores are 40 to 59, above 65 is an elevated score (meaning more concerns than are typically reported)	At each study visit, approximately 3 hours after dose
NIH Toolbox Cognitive Battery	Cognition Fluid Composite, Cognition Crystallized Composite, Cognition Total Composite Score, and other individual test scores	Approximately 3 hours after dose
Methylphenidate plasma levels	Methylphenidate plasma levels will be drawn before and after brain imaging on each visit	Approximately 90 min and 150 min after dose

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Kristin Bigos, PhD, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): April 16, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: October 5, 2023
• First Posted (Actual): October 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: IRB00408678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be deposited in the National Institute of Mental Health Data Archive (NDA) will be collected for each subject. All raw and processed phenotypic data (clinical, cognitive, imaging) will be shared.
• IPD Sharing Time Frame: Data will be deposited at 12 months after the start of recruitment, and every 6 months following
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes