ADHDPhase 1BATNCT05650775
Biomarkers of ADHD Treatment Response
A Phase 1 study testing Concerta and Adderall-XR in people with ADHD, run by Boston Children's Hospital at 1 site in United States.
Trial summary
The goal of this translational biomarker study is to use electroencephalography (EEG) to identify brain signatures that will predict a child's response to two of the most commonly prescribed ADHD medications, methylphenidate and mixed amphetamine salts. The main questions the investigators aim to answer are: 1. Read more about this study
- Who is it for?
- Ages 7 to 11 years
- Conditions the study is for
- ADHD
- What is being tested?
- Concerta and Adderall-XR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2023to 30 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Pediatric patients ages 7-11 seen at the Children's Hospital Primary Care Center
- Have a diagnosis of ADHD or referred for an ADHD evaluation
- Have not previously trialed stimulant medication
Who cannot join
- Diagnoses of intellectual disability, autism, prior suicide attempt, current psychotropic medication use, known genetic syndrome, color-blindness
- History of nonfebrile seizures
- Gestational age < 32 weeks
- Prenatal alcohol or substance exposure
- Medical conditions that contraindicate psychostimulant use (e.g., cardiac concerns).
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this translational biomarker study is to use electroencephalography (EEG) to identify brain signatures that will predict a child's response to two of the most commonly prescribed ADHD medications, methylphenidate and mixed amphetamine salts. The main questions the investigators aim to answer are:
- Do children with ADHD who show symptom reduction with methylphenidate have different EEG profiles than children who do not respond well to methylphenidate?
- Do children who respond better to mixed amphetamine salts than to methylphenidate have unique EEG profiles?
The investigators will measure brain activity before the participating children have tried any stimulant medications, and then again after a 3-week trial of Concerta (methylphenidate). Participants who do not show significant symptom improvement on Concerta will then complete a 3-week trial of Adderall (mixed amphetamine salts), and the study will measure brain activity while those children are on the best dose of Adderall. The investigators will collect information from the child, caregivers, and teachers each week to measure ADHD symptom improvement and side effects. This study will therefore follow the typical treatment approach used in the Boston Children's Hospital Developmental Medicine Clinic, but the investigators will add measures of brain functioning before and after medication.
Read the detailed description
Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder associated with psychiatric, social, academic, occupational, and health impairments across the lifetime. Although pharmacological interventions for pediatric ADHD are safe and effective, there is considerable variability in treatment response at the individual level. As a result, identification of optimal medication class and dose is often not attained in community clinical settings. The current application constitutes a translational biomarkers study aimed at identifying electroencephalography (EEG) and event related potential (ERP) biomarkers of preferential response to two commonly prescribed psychostimulants among children with ADHD. The results of this investigation will improve understanding of individual differences in neurobiological mechanisms of ADHD and provide preliminary data for a large-scale clinical trial aimed at developing a precision medicine care model for pharmacological treatment of ADHD.
With the support of the Translational Neuroscience Center Clinical Research Operations services and in collaboration with the Boston Children's Hospital Primary Care Center (CHPCC), the investigators will execute a sequential crossover design study examining pre-treatment EEG and ERP biomarkers of response to methylphenidate (MPH; Concerta) among all children and to mixed amphetamine salts (MAS; Adderall-XR) among children with suboptimal response to MPH. Additional pre- and post-treatment assessments will be integrated with standard clinical care provided by Dr. Chan (co-PI) in the Division of Developmental Medicine. The study will recruit 30 stimulant-treatment-naïve children with ADHD, ages 7-11, from the CHPCC. Additionally, analyses will capitalize on Dr. Arnett's (co-PI) existing EEG/ERP data on 40 typically developing (TD) children in the same age range to maximize power for statistical comparisons.
The investigators hypothesize that, consistent with Dr. Arnett's prior work, the EEG and ERP profiles will differentiate children with positive response to MPH versus preferential response to MAS. Specifically, the investigators hypothesize that MPH responders will have reduced P3 ERP amplitude and normal aperiodic spectral slope, while MAS preferential responders will have normal P3 amplitude and flatter aperiodic spectral slope. The investigators expect that slow individual alpha peak will be associated with reduced response to both MPH and MAS, as suggested by prior literature. Additionally, the investigators hypothesize that at optimal dosing, treatment-related change in EEG/ERP biomarkers will be associated with ADHD symptom improvement; this will indicate that individual differences in psychostimulant response reflect individual differences in the neurobiological etiology of ADHD symptoms.
The results of this pilot study will support application for federal funding for a large-scale clinical trial. The long-term outcomes of this line of research stand to benefit children and families with ADHD, as well as children with other primary diagnoses commonly associated with ADHD (e.g., autism spectrum disorder; genetic syndromes). Moreover, differences in neurophysiological correlates of differential stimulant response have potential to increase our knowledge of neural mechanisms underlying psychostimulant medication effects.
- Conditions
- ADHD
- Being tested
- Concerta, Adderall-XR
- Keywords
- Electroencephalography, ADHD, Event related potentials, Stimulants
- 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.
ConcertaDrug
3-week trial of oral methylphenidate extended release
Adderall-XRDrug
3-week trial of oral mixed amphetamine salts, extended release, administered only to children who do not show at least 30% improvement during the Concerta/Methylphenidate trial.
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate Trial | Active comparator | 3-week methylphenidate trial with weekly dose adjustments. Receives: Drug: Concerta |
| Mixed Amphetamine Salts Trial | Active comparator | 3-week trial of mixed amphetamine salts with weekly dose adjustments. Receives: Drug: Adderall-XR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ADHD Symptom Severity from Baseline to End of Concerta Trial
Vanderbilt ADHD Ratings from the parent and teacher will be collected at baseline and weekly during each of the 3-week medication trials to guide further dosing and study disposition. Patients with at least 30% ADHD symptom reduction on both parent and teacher rating scales at the end of the 3-week Concerta trial will return to standard clinical care with their primary care provider. Patients with less than 30% ADHD symptom reduction at the end of the 3-week Concerta/Methylphenidate trial will complete a 1-2 week medication washout and then a 3-week Adderall-XR trial. Vanderbilt items are rated on a scale of 0-3 and averaged. Higher scores indicate more symptoms.
Measured: Baseline and Concerta Trial Week 3
Change in ADHD Symptom Severity from Baseline to End of Adderall-XR Trial
Vanderbilt ADHD Ratings from the parent and teacher will be collected at baseline and weekly during each of the 3-week medication trials to guide further dosing and study disposition. Vanderbilt items are rated on a scale of 0-3 and averaged. Higher scores indicate more symptoms.
Measured: Baseline and Adderall-XR Trial Week 3
Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment on Concerta
Change in functioning and ADHD-related impairment will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) after 3 weeks of the Concerta trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Measured: Concerta Trial Week 3
Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment on Adderall-XR
Change in functioning and ADHD-related impairment will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) after 3 weeks of the Adderall-XR trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Measured: Adderall-XR Trial Week 3
Long-Term Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment
Change in functioning and ADHD-related impairment from Baseline to post-treatment will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) 3 months after the final medication trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Measured: 3 Months After Trial Completion
Long-Term Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment
Change in functioning and ADHD-related impairment from Baseline to post-treatment, and maintenance of improvement will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) 6 months after the final medication trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Measured: 6 Months After Trial Completion
Baseline EEG Resting Aperiodic Slope
EEG resting aperiodic spectral slope will be derived from the lights-off resting paradigm at baseline, with the hypothesis that unmedicated individual aperiodic slope will predict treatment response to Concerta and/or Adderall-XR. Aperiodic slope will be quantified as the aperiodic exponent from 1-55 hz using the FOOOF toolbox in MATLAB.
Measured: Baseline
Baseline EEG Resting Alpha Peak Frequency
EEG resting alpha peak frequency will be derived from the lights-off resting paradigm at baseline, with the hypothesis that unmedicated individual alpha peak frequency will predict treatment response to Concerta and/or Adderall-XR. Alpha peak frequency will be quantified as the highest peak between 7-13 hz for which there is lower power .2 hz below and .2 hz above, indicating a true peak rather than a local maximum.
Measured: Baseline
Baseline EEG Novelty P3 Amplitude
Average P3 amplitude derived from novel stimuli in a visual oddball task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that unmedicated individual novelty P3 amplitude will predict treatment response to Concerta and/or Adderall-XR.
Measured: Baseline
Baseline EEG Cued P3 Amplitude
Average P3 amplitude derived from cue stimuli in a cued go-no-go task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that unmedicated individual cued P3 amplitude will predict treatment response to Concerta and/or Adderall-XR.
Measured: Baseline
Change in EEG Resting Aperiodic Slope on Concerta
EEG resting aperiodic spectral slope will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Concerta Trial while the child is on their optimal dose of Concerta.
Measured: Baseline and Post-Concerta Trial
Change in EEG Alpha Peak Frequency on Concerta
EEG resting alpha peak frequency will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Concerta Trial while the child is on their optimal dose of Concerta.
Measured: Baseline and Post-Concerta Trial
Change in Novelty P3 ERP Amplitude on Concerta
Average P3 amplitude derived from novel stimulus trials in a visual oddball task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in novelty P3 amplitude from Baseline to optimal dose of Concerta will be associated with change in ADHD symptom severity.
Measured: Baseline and Post-Concerta Trial
Change in Cued P3 ERP Amplitude on Concerta
Average P3 amplitude derived from cue stimuli in a cued go-no-go task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in cue P3 amplitude from Baseline to optimal dose of Concerta will be associated with change in ADHD symptom severity.
Measured: Baseline and Post-Concerta Trial
Change in EEG Resting Aperiodic Slope on Adderall-XR
EEG resting aperiodic spectral slope will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Adderall-XR Trial while the child is on their optimal dose of Adderall-XR.
Measured: Baseline and Post-Adderall-XR Trial
Change in EEG Alpha Peak Frequency on Adderall-XR
EEG resting alpha peak frequency will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Adderall-XR Trial while the child is on their optimal dose of Adderall-XR.
Measured: Baseline and Post-Adderall-XR Trial
Change in Novelty P3 ERP Amplitude on Adderall-XR
Average P3 amplitude derived from novel stimulus trials in a visual oddball task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in novelty P3 amplitude from Baseline to optimal dose of Adderall-XR will be associated with change in ADHD symptom severity.
Measured: Baseline and Post-Adderall-XR Trial
Change in Cue P3 ERP Amplitude on Adderall-XR
Average P3 amplitude derived from cue stimuli in a cued go-no-go task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in cue P3 amplitude from Baseline to optimal dose of Adderall-XR will be associated with change in ADHD symptom severity.
Measured: Baseline and Post-Adderall-XR Trial
Secondary outcomes (14)
Medication Tolerance to Concerta
In addition to symptom reduction, treatment side effects and tolerance will be examined as a secondary endpoint. Severity of side effects will be rated by the parent and teacher on the ADHD Vanderbilt Rating scales at baseline and weekly during the 3-week Concerta trial. At the end of the 3-week trial, each child will be assigned a summary tolerance rating by the research team: 1 = no side effects, 2=mild side effects, or 3=significant side effects requiring treatment discontinuation.
Measured: Post-Concerta Trial
Medication Tolerance to Adderall-XR
In addition to symptom reduction, treatment side effects and tolerance will be examined as a secondary endpoint. Severity of side effects will be rated by the parent and teacher on the ADHD Vanderbilt Rating scales at baseline and weekly during the 3-week Adderall-XR trial. At the end of the 3-week trial, each child will be assigned a summary tolerance rating by the research team: 1 = no side effects, 2=mild side effects, or 3=significant side effects requiring treatment discontinuation.
Measured: Post-Adderall-XR Trial
Change in Tests of Variables of Attention (TOVA) Commission errors on Concerta
Commission errors on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Concerta trial when the patient is on their optimal dose of Concerta as a measure of treatment effects on inhibitory control. TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Concerta Trial
Change in Tests of Variables of Attention (TOVA) Commission errors on Adderall-XR
Commission errors on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Adderall-XR trial when the patient is on their optimal dose of Adderall-XR, as a measure of treatment effects on inhibitory control. TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Adderall-XR Trial
Tests of Variables of Attention (TOVA) Response Time on Concerta
Response time on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Concerta trial when the patient is on their optimal dose of Concerta, as a measure of treatment effects on response time (speed). TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Concerta Trial
Tests of Variables of Attention (TOVA) Response Time on Adderall-XR
Response time on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Adderall-XR trial when the patient is on their optimal dose of Adderall-XR, as a measure of treatment effects on response time (speed). TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Adderall-XR Trial
Tests of Variables of Attention (TOVA) Omission Errors on Concerta
Omission errors on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Concerta trial when the patient is on their optimal dose of Concerta, as a measure of treatment effects on attention maintenance. TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Concerta Trial
Tests of Variables of Attention (TOVA) Omission Errors on Adderall-XR
Omission errors on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Adderall-XR trial when the patient is on their optimal dose of Adderall-XR, as a measure of treatment effects on attention maintenance. TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Adderall-XR Trial
Tests of Variables of Attention (TOVA) Variability in Response Time on Concerta
Variability of response time on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Concerta trial when the patient is on their optimal dose of Concerta, as a measure of treatment effects on response time variability (consistency). TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Concerta Trial
Tests of Variables of Attention (TOVA) Variability in Response Time on Adderall-XR
Variability of response time on the Tests of Variables of Attention (TOVA) will be examined at baseline and at the end of the 3-week Adderall-XR trial when the patient is on their optimal dose of Adderall-XR, as a measure of treatment effects on response time variability (consistency). TOVA scores are reported as standard scores with a mean of 100 and standard deviation of 15 (range: <40 - >120). Higher scores indicate better performance.
Measured: Baseline and Post-Adderall-XR Trial
Change in Internalizing Symptoms
Longitudinal associations between ADHD symptom reduction and internalizing symptoms (depression, anxiety) will be measured using the Behavior Assessment System for Children, 3rd Edition (BASC-3) Internalizing Scale at Baseline and at 3 months after study completion. Longitudinal bivariate associations will be modeled using an autoregressive cross-lagged path model. BASC-3 scores are reported as T-scores with a mean of 50 and standard deviation of 10 (range: 20-120). Higher scores indicate more pathology.
Measured: Baseline & 3 months after trial completion
Long-term Change in Internalizing Symptoms
Longitudinal associations between ADHD symptom reduction and internalizing symptoms (depression, anxiety) will be measured using the Behavior Assessment System for Children, 3rd Edition (BASC-3) Internalizing Scale at Baseline and at 6 months after study completion. Longitudinal bivariate associations will be modeled using an autoregressive cross-lagged path model. BASC-3 scores are reported as T-scores with a mean of 50 and standard deviation of 10 (range: 20-120). Higher scores indicate more pathology.
Measured: Baseline & 6 months after trial completion
Change in Externalizing Symptoms
Longitudinal associations between ADHD symptom reduction and externalizing symptoms (oppositional defiance, aggression, conduct problems) will be measured using the Behavior Assessment System for Children, 3rd Edition (BASC-3) Externalizing Scale at Baseline and at 3 months after trial completion. Bivariate associations will be modeled across all 3 time points using an autoregressive cross-lagged path model. BASC-3 scores are reported as T-scores with a mean of 50 and standard deviation of 10 (range: 20-120). Higher scores indicate more pathology.
Measured: Baseline and 3 months after trial completion
Long-term Change in Externalizing Symptoms
Longitudinal associations between ADHD symptom reduction and externalizing symptoms (oppositional defiance, aggression, conduct problems) will be measured using the Behavior Assessment System for Children, 3rd Edition (BASC-3) Externalizing Scale at Baseline and at 6 months after trial completion. Bivariate associations will be modeled across all 3 time points using an autoregressive cross-lagged path model. BASC-3 scores are reported as T-scores with a mean of 50 and standard deviation of 10 (range: 20-120). Higher scores indicate more pathology.
Measured: Baseline and 6 months after trial completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2022
- Study start17 Feb 2023
- Primary completion30 Mar 2024
- Study completion30 Mar 2024
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is a sequential partial-crossover design. All participants will complete the Baseline visit, the methylphenidate trial, and a follow-up lab visit. Participants with \< 30% symptom improvement on methylphenidate will then complete a 1-2 week washout, followed by a trial of mixed amphetamine salts and a second follow-up lab visit.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anne Arnett, Boston Children's Hospital
- Investigators
- Anne B Arnett, PhD, Principal investigator, Boston Children's HospitalEugenia Chan, MD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05650775
- Sponsor's protocol ID
- ArnettChanTNC2022
- Acronym
- BAT
- Status last verified
- Dec 2024
- First submitted
- 1 Nov 2022
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: De-identified EEG, behavioral and cognitive data may be made available to researchers upon request.
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of ADHD Treatment Response
- ClinicalTrials.gov ID
- NCT05650775
- Acronym / sponsor ID
- BAT / ArnettChanTNC2022
- Conditions
- ADHD
- Keywords
- Electroencephalography, ADHD, Event related potentials, Stimulants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 17 Feb 2023 (actual)
- Primary completion
- 30 Mar 2024 (actual)
- Study completion
- 30 Mar 2024 (actual)
- First posted
- 14 Dec 2022 (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.
The goal of this translational biomarker study is to use electroencephalography (EEG) to identify brain signatures that will predict a child's response to two of the most commonly prescribed ADHD medications, methylphenidate and mixed amphetamine salts. The main questions the investigators aim to answer are:
- Do children with ADHD who show symptom reduction with methylphenidate have different EEG profiles than children who do not respond well to methylphenidate?
- Do children who respond better to mixed amphetamine salts than to methylphenidate have unique EEG profiles?
The investigators will measure brain activity before the participating children have tried any stimulant medications, and then again after a 3-week trial of Concerta (methylphenidate). Participants who do not show significant symptom improvement on Concerta will then complete a 3-week trial of Adderall (mixed amphetamine salts), and the study will measure brain activity while those children are on the best dose of Adderall. The investigators will collect information from the child, caregivers, and teachers each week to measure ADHD symptom improvement and side effects. This study will therefore follow the typical treatment approach used in the Boston Children's Hospital Developmental Medicine Clinic, but the investigators will add measures of brain functioning before and after medication.
Detailed description
Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder associated with psychiatric, social, academic, occupational, and health impairments across the lifetime. Although pharmacological interventions for pediatric ADHD are safe and effective, there is considerable variability in treatment response at the individual level. As a result, identification of optimal medication class and dose is often not attained in community clinical settings. The current application constitutes a translational biomarkers study aimed at identifying electroencephalography (EEG) and event related potential (ERP) biomarkers of preferential response to two commonly prescribed psychostimulants among children with ADHD. The results of this investigation will improve understanding of individual differences in neurobiological mechanisms of ADHD and provide preliminary data for a large-scale clinical trial aimed at developing a precision medicine care model for pharmacological treatment of ADHD.
With the support of the Translational Neuroscience Center Clinical Research Operations services and in collaboration with the Boston Children's Hospital Primary Care Center (CHPCC), the investigators will execute a sequential crossover design study examining pre-treatment EEG and ERP biomarkers of response to methylphenidate (MPH; Concerta) among all children and to mixed amphetamine salts (MAS; Adderall-XR) among children with suboptimal response to MPH. Additional pre- and post-treatment assessments will be integrated with standard clinical care provided by Dr. Chan (co-PI) in the Division of Developmental Medicine. The study will recruit 30 stimulant-treatment-naïve children with ADHD, ages 7-11, from the CHPCC. Additionally, analyses will capitalize on Dr. Arnett's (co-PI) existing EEG/ERP data on 40 typically developing (TD) children in the same age range to maximize power for statistical comparisons.
The investigators hypothesize that, consistent with Dr. Arnett's prior work, the EEG and ERP profiles will differentiate children with positive response to MPH versus preferential response to MAS. Specifically, the investigators hypothesize that MPH responders will have reduced P3 ERP amplitude and normal aperiodic spectral slope, while MAS preferential responders will have normal P3 amplitude and flatter aperiodic spectral slope. The investigators expect that slow individual alpha peak will be associated with reduced response to both MPH and MAS, as suggested by prior literature. Additionally, the investigators hypothesize that at optimal dosing, treatment-related change in EEG/ERP biomarkers will be associated with ADHD symptom improvement; this will indicate that individual differences in psychostimulant response reflect individual differences in the neurobiological etiology of ADHD symptoms.
The results of this pilot study will support application for federal funding for a large-scale clinical trial. The long-term outcomes of this line of research stand to benefit children and families with ADHD, as well as children with other primary diagnoses commonly associated with ADHD (e.g., autism spectrum disorder; genetic syndromes). Moreover, differences in neurophysiological correlates of differential stimulant response have potential to increase our knowledge of neural mechanisms underlying psychostimulant medication effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a sequential partial-crossover design. All participants will complete the Baseline visit, the methylphenidate trial, and a follow-up lab visit. Participants with < 30% symptom improvement on methylphenidate will then complete a 1-2 week washout, followed by a trial of mixed amphetamine salts and a second follow-up lab visit.
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate Trial | Active comparator | Drug: Concerta3-week methylphenidate trial with weekly dose adjustments. |
| Mixed Amphetamine Salts Trial | Active comparator | Drug: Adderall-XR3-week trial of mixed amphetamine salts with weekly dose adjustments. |
Who may qualify
- Ages
- 7 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Pediatric patients ages 7-11 seen at the Children's Hospital Primary Care Center
- Have a diagnosis of ADHD or referred for an ADHD evaluation
- Have not previously trialed stimulant medication
Key exclusion criteria (5 listed)
- Diagnoses of intellectual disability, autism, prior suicide attempt, current psychotropic medication use, known genetic syndrome, color-blindness
- History of nonfebrile seizures
- Gestational age < 32 weeks
- Prenatal alcohol or substance exposure
- Medical conditions that contraindicate psychostimulant use (e.g., cardiac concerns).
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 |
|---|---|---|
| Concerta3-week trial of oral methylphenidate extended release | Drug | Methylphenidate Trial |
| Adderall-XR3-week trial of oral mixed amphetamine salts, extended release, administered only to children who do not show at least 30% improvement during the Concerta/Methylphenidate trial. | Drug | Mixed Amphetamine Salts Trial |
Primary outcome
Change in ADHD Symptom Severity from Baseline to End of Concerta Trial
Time frame: Baseline and Concerta Trial Week 3
Vanderbilt ADHD Ratings from the parent and teacher will be collected at baseline and weekly during each of the 3-week medication trials to guide further dosing and study disposition. Patients with at least 30% ADHD symptom reduction on both parent and teacher rating scales at the end of the 3-week Concerta trial will return to standard clinical care with their primary care provider. Patients with less than 30% ADHD symptom reduction at the end of the 3-week Concerta/Methylphenidate trial will complete a 1-2 week medication washout and then a 3-week Adderall-XR trial. Vanderbilt items are rated on a scale of 0-3 and averaged. Higher scores indicate more symptoms.
Change in ADHD Symptom Severity from Baseline to End of Adderall-XR Trial
Time frame: Baseline and Adderall-XR Trial Week 3
Vanderbilt ADHD Ratings from the parent and teacher will be collected at baseline and weekly during each of the 3-week medication trials to guide further dosing and study disposition. Vanderbilt items are rated on a scale of 0-3 and averaged. Higher scores indicate more symptoms.
Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment on Concerta
Time frame: Concerta Trial Week 3
Change in functioning and ADHD-related impairment will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) after 3 weeks of the Concerta trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment on Adderall-XR
Time frame: Adderall-XR Trial Week 3
Change in functioning and ADHD-related impairment will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) after 3 weeks of the Adderall-XR trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Long-Term Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment
Time frame: 3 Months After Trial Completion
Change in functioning and ADHD-related impairment from Baseline to post-treatment will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) 3 months after the final medication trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Long-Term Clinical Global Impressions-Improvement (CGI-I) in ADHD-related impairment
Time frame: 6 Months After Trial Completion
Change in functioning and ADHD-related impairment from Baseline to post-treatment, and maintenance of improvement will be measured with the Clinical Global Impressions-Improvement scale (CGI-I) 6 months after the final medication trial. Ratings are made by the clinician on a scale of 1-7, with lower scores indicating fewer symptoms after treatment. Consistent with previous research, scores of 2 "much improved" or 1 "very much improved" will be considered clinically significant improvement and will be used to categorize patients as treatment responders for analyses.
Baseline EEG Resting Aperiodic Slope
Time frame: Baseline
EEG resting aperiodic spectral slope will be derived from the lights-off resting paradigm at baseline, with the hypothesis that unmedicated individual aperiodic slope will predict treatment response to Concerta and/or Adderall-XR. Aperiodic slope will be quantified as the aperiodic exponent from 1-55 hz using the FOOOF toolbox in MATLAB.
Baseline EEG Resting Alpha Peak Frequency
Time frame: Baseline
EEG resting alpha peak frequency will be derived from the lights-off resting paradigm at baseline, with the hypothesis that unmedicated individual alpha peak frequency will predict treatment response to Concerta and/or Adderall-XR. Alpha peak frequency will be quantified as the highest peak between 7-13 hz for which there is lower power .2 hz below and .2 hz above, indicating a true peak rather than a local maximum.
Baseline EEG Novelty P3 Amplitude
Time frame: Baseline
Average P3 amplitude derived from novel stimuli in a visual oddball task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that unmedicated individual novelty P3 amplitude will predict treatment response to Concerta and/or Adderall-XR.
Baseline EEG Cued P3 Amplitude
Time frame: Baseline
Average P3 amplitude derived from cue stimuli in a cued go-no-go task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that unmedicated individual cued P3 amplitude will predict treatment response to Concerta and/or Adderall-XR.
Change in EEG Resting Aperiodic Slope on Concerta
Time frame: Baseline and Post-Concerta Trial
EEG resting aperiodic spectral slope will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Concerta Trial while the child is on their optimal dose of Concerta.
Change in EEG Alpha Peak Frequency on Concerta
Time frame: Baseline and Post-Concerta Trial
EEG resting alpha peak frequency will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Concerta Trial while the child is on their optimal dose of Concerta.
Change in Novelty P3 ERP Amplitude on Concerta
Time frame: Baseline and Post-Concerta Trial
Average P3 amplitude derived from novel stimulus trials in a visual oddball task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in novelty P3 amplitude from Baseline to optimal dose of Concerta will be associated with change in ADHD symptom severity.
Change in Cued P3 ERP Amplitude on Concerta
Time frame: Baseline and Post-Concerta Trial
Average P3 amplitude derived from cue stimuli in a cued go-no-go task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in cue P3 amplitude from Baseline to optimal dose of Concerta will be associated with change in ADHD symptom severity.
Change in EEG Resting Aperiodic Slope on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
EEG resting aperiodic spectral slope will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Adderall-XR Trial while the child is on their optimal dose of Adderall-XR.
Change in EEG Alpha Peak Frequency on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
EEG resting alpha peak frequency will be derived from the lights-off resting paradigm at Baseline (unmedicated) and at the end of the Adderall-XR Trial while the child is on their optimal dose of Adderall-XR.
Change in Novelty P3 ERP Amplitude on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
Average P3 amplitude derived from novel stimulus trials in a visual oddball task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in novelty P3 amplitude from Baseline to optimal dose of Adderall-XR will be associated with change in ADHD symptom severity.
Change in Cue P3 ERP Amplitude on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
Average P3 amplitude derived from cue stimuli in a cued go-no-go task will be measured as the mean amplitude in a window determined via visual inspection and literature review. The hypothesis is that change in cue P3 amplitude from Baseline to optimal dose of Adderall-XR will be associated with change in ADHD symptom severity.
14 secondary outcomes
Medication Tolerance to Concerta
Time frame: Post-Concerta Trial
Medication Tolerance to Adderall-XR
Time frame: Post-Adderall-XR Trial
Change in Tests of Variables of Attention (TOVA) Commission errors on Concerta
Time frame: Baseline and Post-Concerta Trial
Change in Tests of Variables of Attention (TOVA) Commission errors on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
Tests of Variables of Attention (TOVA) Response Time on Concerta
Time frame: Baseline and Post-Concerta Trial
Tests of Variables of Attention (TOVA) Response Time on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
Tests of Variables of Attention (TOVA) Omission Errors on Concerta
Time frame: Baseline and Post-Concerta Trial
Tests of Variables of Attention (TOVA) Omission Errors on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
Tests of Variables of Attention (TOVA) Variability in Response Time on Concerta
Time frame: Baseline and Post-Concerta Trial
Tests of Variables of Attention (TOVA) Variability in Response Time on Adderall-XR
Time frame: Baseline and Post-Adderall-XR Trial
Change in Internalizing Symptoms
Time frame: Baseline & 3 months after trial completion
Long-term Change in Internalizing Symptoms
Time frame: Baseline & 6 months after trial completion
Change in Externalizing Symptoms
Time frame: Baseline and 3 months after trial completion
Long-term Change in Externalizing Symptoms
Time frame: Baseline and 6 months after trial completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Individual participant dataSharing planned: Undecided. De-identified EEG, behavioral and cognitive data may be made available to researchers upon request.
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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. This study is not recruiting at the moment.
Anne B Arnett, PhD principal investigator
Boston Children's Hospital
Eugenia Chan, MD principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Concerta and Adderall-XR 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 3 inclusion and 5 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: finished, as of the sponsor's last update on 18 Dec 2024. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ADHD Symptom Severity from Baseline to End of Concerta Trial (time frame: Baseline and Concerta Trial Week 3). The study lists 18 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 18 Dec 2024.