ADHDPhase 4NCT07650643
EEG Biomarkers for ADHD Stimulant Treatment
A Phase 4 study testing methylphenidate HCl and Mixed amphetamine salts extended release in people with ADHD, run by Boston Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 11 years
- Conditions the study is for
- ADHD
- What is being tested?
- methylphenidate HCl and Mixed amphetamine salts extended release
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2026to 31 Aug 2031
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Boston Children's Hospital at Two Brookline Place
Brookline, Massachusetts, 02445
Anne Arnett, 9788861658, anne.arnett@childrens.harvard.edu
About this study
Official title: 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.
Read more
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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Read the 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.
- Conditions
- ADHD
- Being tested
- methylphenidate HCl, Mixed amphetamine salts extended release
- Keywords
- stimulants, EEG, biomarker, randomized crossover, ADHD, treatment, stratification
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methylphenidate HClDrug
3-week titration of liquid Quillivant XR
Mixed amphetamine salts extended releaseDrug
3-week titration of liquid Dyanavel XR
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: methylphenidate HCl; Drug: Mixed amphetamine salts extended release |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
Side Effects Rating Scale, Parent- and Teacher-Report
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.
Measured: 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
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.
Measured: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
N2 Event Related Potential Amplitude
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.
Measured: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
P300 Event Related Potential Amplitude
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.
Measured: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2026
- Study start15 Sep 2026 (estimated)
- Primary completion30 May 2031 (estimated)
- Study completion31 Aug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ADHDStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double blinded, cross-over study with two 3-week treatment arms separated by a 1-week washout.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Seattle Children's Hospital, Tris Pharma, Inc.
- Responsible party
- Principal investigator, Anne Arnett, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07650643
- Sponsor's protocol ID
- P00055002
- Status last verified
- Jun 2026
- First submitted
- 9 Jun 2026
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EEG Biomarkers for Pediatric ADHD Treatment Stratification
- ClinicalTrials.gov ID
- NCT07650643
- Acronym / sponsor ID
- P00055002
- Conditions
- ADHD
- Keywords
- stimulants, EEG, biomarker, randomized crossover, ADHD, treatment, stratification
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Seattle Children's Hospital, Tris Pharma, Inc.
- Study start
- 15 Sep 2026 (estimated)
- Primary completion
- 30 May 2031 (estimated)
- Study completion
- 31 Aug 2031 (estimated)
- First posted
- 16 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double blinded, cross-over study with two 3-week treatment arms separated by a 1-week washout.
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate HCl then Mixed Amphetamines | Experimental | Drug: methylphenidate HCl, Drug: Mixed amphetamine salts extended releaseParticipants 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. |
| Mixed Amphetamines then Methylphenidate HCl | Experimental | Drug: methylphenidate HCl, Drug: Mixed amphetamine salts extended releaseParticipants 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. |
Who may qualify
- Ages
- 7 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methylphenidate HCl3-week titration of liquid Quillivant XR | Drug | Methylphenidate HCl then Mixed Amphetamines, Mixed Amphetamines then Methylphenidate HCl |
| Mixed amphetamine salts extended release3-week titration of liquid Dyanavel XR | Drug | Methylphenidate HCl then Mixed Amphetamines, Mixed Amphetamines then Methylphenidate HCl |
Primary outcome
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.
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.
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.
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.
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.
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.
5 secondary outcomes
P100 Visual Evoked Potential Habituation
Time frame: 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
EEG Coherence
Time frame: 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)
P300 Event Related Potential Amplitude
Time frame: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Individual participant dataSharing planned: Yes. 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
Related trials for ADHD
Enrolling by invitationPhase 3
An Open-Label Study to Assess the Long-Term Safety of Solriamfetol in Children and Adolescents With ADHD
ADHD
Not yet recruitingPhase 2
Lisdexamfetamine For the Treatment of Conduct Disorder in Children
Conduct Disorder
RecruitingObservational study
Augmenting Parent Management Training for Child Temper Outbursts Using a Digital Tool
Disruptive Behavior Disorders, Conduct Disorder
Recruiting
Micronutrient Supplementation and Chronotherapy in Children With ADHD
Attention Deficit Hyperactivity Disorder (ADHD)
RecruitingPhase 3
Forward Treatment of Attention Deficit and Hyperactivity Using Solriamfetol (FOCUS-2)
ADHD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing methylphenidate HCl and Mixed amphetamine salts extended release in people with ADHD, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne B Arnett, PhD (617-919-7771, ArnettLab@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Medication A Clinical Global Impressions - Improvement Scale (CGI-I) (time frame: Week 3 Virtual Visit (Day 22)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.