Multimodal Brain Imaging of Methylphenidate in Children and Adolescents With ADHD

NCT06077669 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: IRB00408678
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ADHD

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• ADHD as assessed by the Connors 3

  At each study visit, approximately 3 hours after dose

• NIH Toolbox Cognitive Battery

  Approximately 3 hours after dose

• Methylphenidate plasma levels

  Approximately 90 min and 150 min after dose

Study Arms (3)

Methylphenidate - low dose

EXPERIMENTAL

5 mg of methylphenidate

Drug: Methylphenidate

Methylphenidate - high dose

EXPERIMENTAL

10 mg of methylphenidate

Drug: Methylphenidate

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

Methylphenidate DRUG

Single oral dose of methylphenidate (5mg or 10 mg)

Also known as: Ritalin

Methylphenidate - high dose; Methylphenidate - low dose

Placebo DRUG

oral placebo

Placebo

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kristin Bigos, PhD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 11, 2023
• Study Start: April 16, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be deposited at 12 months after the start of recruitment, and every 6 months following

Locations

US (1)