EEG Biomarkers for ADHD Stimulant Treatment

June 12, 2026 updated by: Anne Arnett, Boston Children's Hospital

EEG Biomarkers for Pediatric ADHD Treatment Stratification

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. 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. 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. 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. 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. 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. 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. 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. 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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 titration, side effects management, and communication among providers, parents, and school personnel over weeks, months, and years. This level of effort often exceeds the capacity of primary care providers, who manage treatment for the majority of affected children. In the first year following stimulant prescription, recommended routine follow-up occurs in <50% of cases treated in primary care. Consequently, suboptimal dosing and early discontinuation of stimulants are exceedingly common, with >75% pediatric ADHD patients showing suboptimal medication adherence in the first year.

The current proposal will utilize electroencephalography (EEG), a non-invasive, affordable brain measurement tool, to characterize predictive biomarkers for response to two commonly prescribed stimulant medication classes: methylphenidate (MPH) and amphetamines (AMP). Predictive biomarkers can be used to guide clinical decision making and treatment selection for pediatric ADHD, ultimately shortening the time from diagnosis to treatment optimization; reducing burden on clinicians, families, and teachers; and leading to better lifetime outcomes for children with ADHD. Thus far, behavioral- and genomic-based treatment biomarkers have not been successful for ADHD, and there is increasing demand by patients and providers to identify a solution.

Building on our pilot data, this study will constitute a prospective, single-blind, double-baseline randomized MPH-AMP crossover trial with 220 treatment-naïve, 7-11-year-old children with ADHD. EEG will be collected prior to each medication arm, and treatment response will be determined using 3-week rapid titration protocols, consistent with our pilot study and other published trials. Trained clinicians will characterize each participant as a "responder" or "non-responder" for each medication.

EEG features with small to medium effect sizes that are predictive of positive response to MPH and AMP will be identified. Preliminary data suggest MPH and AMP will have distinct EEG predictive biomarkers. To further examine the translational potential of these results, test-retest reliability and classification agreement of biomarkers over 24 hours and 4 weeks will be estimated. Results of this study have potential to accelerate pediatric mental health treatment development and precision medicine care for ADHD.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
220

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Use of stimulants or other psychotropic medications within 7 days before Eligibility Visit
  2. 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
  3. Intellectual disability or IQ < 75 per medical chart review or performance on standardized cognitive testing during the Eligibility Visit
  4. Diagnosis of Autism spectrum disorder (ASD) per medical chart review or caregiver report
  5. Fetal alcohol exposure per medical chart review or caregiver report
  6. Current suicidal ideation per caregiver or child report on CSSRS
  7. Non-febrile seizures per caregiver report or medical chart review
  8. Cardiopulmonary conditions, pregnancy or other medical conditions that contraindicate psychostimulant use per determination by the study MD

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Methylphenidate HCl then Mixed Amphetamines
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
3-week titration of liquid Quillivant XR
Drug: Mixed amphetamine salts extended release
3-week titration of liquid Dyanavel XR
Experimental: Mixed Amphetamines then Methylphenidate HCl
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
3-week titration of liquid Quillivant XR
Drug: Mixed amphetamine salts extended release
3-week titration of liquid Dyanavel XR

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Medication A Clinical Global Impressions - Improvement Scale (CGI-I)
Time Frame: Week 3 Virtual Visit (Day 22)
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)
Time Frame: End of Study Virtual Visit (Day 50)
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
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
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
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
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
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
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
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
P100 Visual Evoked Potential Habituation
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
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. Secondary analyses will focus on P100 amplitude changes over trial, i.e. habituation coefficients.
Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
Side Effects Rating Scale, Parent- and Teacher-Report
Time Frame: 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
Adverse effects associated with stimulant treatment will be recorded by parents and teachers on a weekly basis on the Vanderbilt Follow-Up rating scales, which include an adapted version of the Pittsburgh Side Effects Rating Scale. 12 side effects symptoms are rated on a scale of 0 = not currently a problem to 3 = severe problem. Side effects will be used for clinical decision making. Secondary exploratory analysis will examine associations between EEG features and total severity of side effects by summing ratings from the 12 items.
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
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
EEG coherence will be derived from resting state EEG as well as ERP tasks. Both global (i.e., long-range) and local (i.e., within region of interest) coherence will be examined in exploratory analyses.
Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
N2 Event Related Potential Amplitude
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
The HAPPE+ER pipeline will be used to extract N2 amplitudes during the Go-NoGo task, by condition and electrode. Mean amplitudes will be calculated for components across regions of interest, following visual inspection of temporal and topographic plots.
Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
P300 Event Related Potential Amplitude
Time Frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
The HAPPE+ER pipeline will be used to extract P300 amplitudes during the Go-NoGo task, by condition and electrode. Mean amplitudes will be calculated for components across regions of interest, following visual inspection of temporal and topographic plots.
Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boston Children's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Seattle Children's Hospital
Tris Pharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 9, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 12, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 16, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P00055002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All participants will be given the option to share their de-identified data with research or public registries at the time of informed consent. Data that includes video content (EEG .mff files; assessment videos) will not be shared for ethical reasons. Only de-identified data will be shared. Participants who do not consent to data sharing will still be eligible to participate in this study. All data projected during the study will be preserved by the PIs for the duration required by law in Massachusetts where the data are collected.

To facilitate interpretation of the data, relevant metadata, manual of operations, study protocols, and details regarding data collection tools will be shared and associated with relevant datasets.

Survey data, behavioral assessment scores, EEG and ERP measures will be made available in .csv or .txt format that do not require the use of specialized

IPD Sharing 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.

IPD Sharing Access Criteria

Data will be available to researchers through the NIH supported public database, NDAR, or by reasonable request to the PI.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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