Biomarkers of ADHD Treatment Response

NCT05650775 | Completed Phase 1 FDA Drug

• 1 other identifier: ArnettChanTNC2022
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 1.Do children with ADHD who show symptom reduction with methylphenidate have different EEG profiles than children who do not respond well to methylphenidate?
2. 2.Do children who respond better to mixed amphetamine salts than to methylphenidate have unique EEG profiles?

Conditions

ADHD

Keywords

Electroencephalography; ADHD; Event related potentials; Stimulants

Outcome Measures

Primary Outcomes (18)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Baseline and Post-Adderall-XR Trial

Secondary Outcomes (14)

• Medication Tolerance to Concerta

  Post-Concerta Trial

• Medication Tolerance to Adderall-XR

  Post-Adderall-XR Trial

• Change in Tests of Variables of Attention (TOVA) Commission errors on Concerta

  Baseline and Post-Concerta Trial

• Change in Tests of Variables of Attention (TOVA) Commission errors on Adderall-XR

  Baseline and Post-Adderall-XR Trial

• Tests of Variables of Attention (TOVA) Response Time on Concerta

  Baseline and Post-Concerta Trial

Study Arms (2)

Methylphenidate Trial

ACTIVE COMPARATOR

3-week methylphenidate trial with weekly dose adjustments.

Drug: Concerta

Mixed Amphetamine Salts Trial

ACTIVE COMPARATOR

3-week trial of mixed amphetamine salts with weekly dose adjustments.

Drug: Adderall-XR

Interventions

Concerta DRUG

3-week trial of oral methylphenidate extended release

Methylphenidate Trial

Adderall-XR DRUG

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.

Mixed Amphetamine Salts Trial

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

2 Brookline Place

Brookline, Massachusetts, 02445, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate; SLI381

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Anne B Arnett, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Eugenia Chan, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: December 14, 2022
• Study Start: February 17, 2023
• Primary Completion: March 30, 2024
• Study Completion: March 30, 2024
• Last Updated: December 18, 2024

Record last verified: 2024-12

Locations

US (1)