EEG Biomarkers for ADHD Stimulant Treatment

NCT07650643 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: P00055002
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Pediatric attention deficit hyperactivity disorder (ADHD) affects up to 10% of children in the U.S. and more than 90% are prescribed stimulant medications according to clinical guidelines. The standard of care for pharmacological treatment of ADHD is a "trial-and-error" approach that requires frequent dose adjustments, side effects management, and communication among doctors, parents, and school personnel over weeks, months, and years. In the first year following prescription of stimulant medications, \>50% of doctors are not able to conduct the recommended follow-up with their patients. Many patients stop taking medications or keep taking medications that do not work well, as a result. This investigation will use a non-invasive brain imaging technique called EEG to look for activity in the brain that can predict which children with ADHD will respond well to two commonly prescribed stimulant medication groups, methylphenidate and amphetamines. Based on a previous study, it is expected that EEG signals can differentiate among children whose ADHD symptoms will get better on methylphenidate, and those whose ADHD symptoms will get better on amphetamines. 220 participants ages 7-11 with ADHD will be enrolled. Participants will not have autism or intellectual disabiltiy. They will not currently be taking psychiatric medications. Participants will not have not taken stimulant medications before or have tried stimulant medications \>6 months or experienced an improvement in their ADHD symptoms by taking a stimulant medication before. Study Participation Includes:

1. 1.Participant and caregiver complete a 3-hour visit at the Arnett Laboratory at 2 Brookline Place. During this visit, participants complete a brief IQ test and an EEG while their caregiver completes questionnaires and a clinical interview. The caregiver will give permission to request survey responses from the participant's teacher.
2. 2.The next day, the participant and caregiver will come back to the laboratory for a 1-hour visit. The participant will do another EEG while the caregiver fills out more surveys. The doctor will take the participant's vital signs and prescribe the medication.
3. 3.The participant will be randomly assigned to take either methylphenidate HCl or amphetamines every morning for 3 weeks. At the end of each week, the caregiver and teacher will fill out a questionnaire about the participant's behaviors and symptoms, including side effects.
4. 4.For one week, the participant will not take medications. They will come back into the lab for another EEG at the end of that week.
5. 5.The participant will then take the other medication every morning for 3 weeks. At the end of each week, the caregiver and teacher will fill out a questionnaire about the participant's behaviors and symptoms, including side effects.
6. 6.It will take participants about 7 weeks to complete this study. During this time, they will complete 3 in-person and 6 virtual study visits.
7. 7.The research funds will cover cost associated with the study. The participant's health insurer will not be billed for the medications or treatment. Medications will be provided through the research pharmacy.
8. 8.Participants will be given a report at the end of the study with details about the medication trials, symptom response, and any other findings. They will receive up to $270 for the completion of the study. Some travel-related costs will be covered by the study.

Conditions

ADHD

Keywords

stimulants; EEG; biomarker; randomized crossover; ADHD; treatment; stratification

Outcome Measures

Primary Outcomes (6)

• Medication A Clinical Global Impressions - Improvement Scale (CGI-I)

  Clinician rating of participant ADHD symptom improvement on medication A. The Clinical Global Impressions - Improvement Scale (CGI-I) is rated by a trained study clinician on a scale of 1-7, with scores of 1 ("very much improved") and 2 ("much improved") corresponding to clinically significant symptom improvement. Scores of 3-7 will indicate no improvement or worsening of symptoms.

  Week 3 Virtual Visit (Day 22)

• Medication B Clinical Global Impressions - Improvement Scale (CGI-I)

  Clinician rating of participant ADHD symptom improvement on medication B. The Clinical Global Impressions - Improvement Scale (CGI-I) is rated by a trained study clinician on a scale of 1-7, with scores of 1 ("very much improved") and 2 ("much improved") corresponding to clinically significant symptom improvement. Scores of 3-7 will indicate no improvement or worsening of symptoms.

  End of Study Virtual Visit (Day 50)

• Frontal Theta Beta Ratio

  Theta-Beta Ratio (TBR): TBR will be calculated from periodic resting EEG. Periodic power isolates the oscillatory component of the EEG by subtracting the aperiodic power spectra from the total power. Periodic power is extracted with the Fitting Oscillations and One-Over-f (FOOOF) MATLAB toolbox which parametrizes resting state EEG data into aperiodic and periodic components. Resting spectral power values will be averaged over theta (4-6 Hz) and beta (13-30 Hz) frequencies across midline electrode clusters (frontal: Fz, F3, F4; central: Cz, C3, C4; parietal: Pz, P3, P4; occipital: Oz, O1, O2). Our primary analyses will focus on frontal TBR during the Lights-Off Resting condition.

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

• Aperiodic Dynamics

  Aperiodic Dynamics: The aperiodic exponent for lights-off and lights-on resting conditions will be averaged across midline electrode clusters FOOOF MATLAB toolbox. Aperiodic dynamic values will be computed for each participant as the difference between lights-on and lights-off exponent, divided by the lights-off resting exponent, as in prior publications. Thus, higher scores will indicate greater exponents in the lights-on experiment. Primary analyses will use the central electrode cluster.

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

• P100 Visual Evoked Potential Amplitude

  VEP P100 Amplitudes. The P100 VEP component will be derived from a passive pattern-reversal visual evoked potential (VEP) task that includes 200 500ms trials of a black and white checkerboard reversal over 3 minutes. P100 amplitudes will be averaged over an occipital electrode cluster (Oz, O1, O2) from approximately 75-150ms and extracted for each trial. Primary analyses will focus on mean VEP amplitude over trials.

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

• Vanderbilt Rating Scales

  The Vanderbilt Rating Scales include 18 items corresonding to DSM-5 ADHD symptoms. Parents and teachers will each complete the scales using an electronic form. Items are rated on a scale of 0-3, with 0 = symptom never or rarely occurs, and 3 = symptom often or almost always occurs. Total symptom severity is calculated as the sum of all 18 items; inattention symptom severity is calculated as the sum of items 1-9; hyperactivity/impulsivity symptom severity is calculated as the sum of items 10-18.

  Baseline, Medication A Week 1, Medication A Week 2, Medication A Week 3, Crossover Week 4, Medication B Week 5, Medication B Week 6, End of Study Week 7

Secondary Outcomes (5)

• P100 Visual Evoked Potential Habituation

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

• Side Effects Rating Scale, Parent- and Teacher-Report

  Baseline, Medication A Week 1, Medication A Week 2, Medication A Week 3, Crossover Week 4, Medication B Week 5, Medication B Week 6, End of Study Week 7

• EEG Coherence

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

• N2 Event Related Potential Amplitude

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

• P300 Event Related Potential Amplitude

  Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

Study Arms (2)

Methylphenidate HCl then Mixed Amphetamines

EXPERIMENTAL

Participants in the first Arm will complete a 3-week titration of Methylphenidate HCl (Quillivant XR, 25mg/5mL). Doses will be increased at the end of each week using the following schedule: week 1 2mL; week 2 4mL; week 3 6mL. If intolerable side effects develop, the dose will be reduced to the previously tolerated level or the medication will be discontinued if no tolerable therapeutic dose can be identified. Next, participants will complete a 1-week no-medication washout (range = 5-14 days allowed to accomodate participant schedules). Lastly, participants will complete a 3-week titration of Mixed Amphetamines (Dyanavel XR, 2.5mg/1mL). Doses will be increased at the end of each week using the following schedule: week 1 2mL; week 2 3mL; week 3 4mL. If intolerable side effects develop, the dose will be reduced to the previously tolerated level or the medication will be discontinued if no tolerable therapeutic dose can be identified.

Drug: methylphenidate HCl; Drug: Mixed amphetamine salts extended release

Mixed Amphetamines then Methylphenidate HCl

EXPERIMENTAL

Participants in the second Arm will complete a 3-week titration of Mixed Amphetamines (Dyanavel XR, 2.5mg/1mL). Doses will be increased at the end of each week using the following schedule: week 1 2mL; week 2 3mL; week 3 4mL. If intolerable side effects develop, the dose will be reduced to the previously tolerated level or the medication will be discontinued if no tolerable therapeutic dose can be identified. Next, participants will complete a 1-week no-medication washout (range = 5-14 days allowed to accomodate participant schedules). Lastly, participants will complete a 3-week titration of Methylphenidate HCl (Quillivant XR, 25mg/5mL). Doses will be increased at the end of each week using the following schedule: week 1 2mL; week 2 4mL; week 3 6mL. If intolerable side effects develop, the dose will be reduced to the previously tolerated level or the medication will be discontinued if no tolerable therapeutic dose can be identified.

Drug: methylphenidate HCl; Drug: Mixed amphetamine salts extended release

Interventions

methylphenidate HCl DRUG

3-week titration of liquid Quillivant XR

Methylphenidate HCl then Mixed Amphetamines; Mixed Amphetamines then Methylphenidate HCl

Mixed amphetamine salts extended release DRUG

3-week titration of liquid Dyanavel XR

Methylphenidate HCl then Mixed Amphetamines; Mixed Amphetamines then Methylphenidate HCl

Eligibility Criteria

• Age: 7 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Ages 7:0 - 10:11 (years:months)
• Has a diagnosis of ADHD or being evaluated for ADHD
• Stimulant naïve or previously trialed stimulant medications for \< 6 months without achieving symptom remission, per caregiver report and/or medical chart review (if available)
• CGI-Severity rating of 4 "Moderately ill" through 6 "Severely ill."
• Willing and able to comply with study procedures

You may not qualify if:

• Use of stimulants or other psychotropic medications within 7 days before Eligibility Visit
• History of severe side effects to stimulants (suicidality, complete loss of appetite, cardiopulmonary complications) per caregiver report or medical chart review, determined by the study MD
• Intellectual disability or IQ \< 75 per medical chart review or performance on standardized cognitive testing during the Eligibility Visit
• Diagnosis of Autism spectrum disorder (ASD) per medical chart review or caregiver report
• Fetal alcohol exposure per medical chart review or caregiver report
• Current suicidal ideation per caregiver or child report on CSSRS
• Non-febrile seizures per caregiver report or medical chart review
• Cardiopulmonary conditions, pregnancy or other medical conditions that contraindicate psychostimulant use per determination by the study MD

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Seattle Children's Hospital: collaborator
• Tris Pharma, Inc.: collaborator

Study Sites (1)

Boston Children's Hospital at Two Brookline Place

Brookline, Massachusetts, 02445, 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

Central Study Contacts

Anne B Arnett, PhD

CONTACT

617-919-7771; ArnettLab@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Model Details: Randomized, double blinded, cross-over study with two 3-week treatment arms separated by a 1-week washout.

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: June 16, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): May 30, 2031
• Study Completion (Estimated): August 31, 2031
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: De-identified data will be uploaded to NDAR on an ongoing basis, per NIH requirements. Data can also be made available to individual researchers following publication, upon reasonable request.
• Access Criteria: Data will be available to researchers through the NIH supported public database, NDAR, or by reasonable request to the PI.

Locations

US (1)