EEG Biomarkers for ADHD Stimulant Treatment

Официальное название

EEG Biomarkers for Pediatric ADHD Treatment Stratification

Обзор

Pediatric attention deficit hyperactivity disorder (ADHD) affects up to 10% of children in the U.S. and more than 90% are prescribed stimulant medications according to clinical guidelines. The standard of care for pharmacological treatment of ADHD is a "trial-and-error" approach that requires frequent dose adjustments, side effects management, and communication among doctors, parents, and school personnel over weeks, months, and years. In the first year following prescription of stimulant medications, \>50% of doctors are not able to conduct the recommended follow-up with their patients. Many patients stop taking medications or keep taking medications that do not work well, as a result. This investigation will use a non-invasive brain imaging technique called EEG to look for activity in the brain that can predict which children with ADHD will respond well to two commonly prescribed stimulant medication groups, methylphenidate and amphetamines. Based on a previous study, it is expected that EEG signals can differentiate among children whose ADHD symptoms will get better on methylphenidate, and those whose ADHD symptoms will get better on amphetamines. 220 participants ages 7-11 with ADHD will be enrolled. Participants will not have autism or intellectual disabiltiy. They will not currently be taking psychiatric medications. Participants will not have not taken stimulant medications before or have tried stimulant medications \>6 months or experienced an improvement in their ADHD symptoms by taking a stimulant medication before. Study Participation Includes: 1. Participant and caregiver complete a 3-hour visit at the Arnett Laboratory at 2 Brookline Place. During this visit, participants complete a brief IQ test and an EEG while their caregiver completes questionnaires and a clinical interview. The caregiver will give permission to request survey responses from the participant's teacher. 2. The next day, the participant and caregiver will come back to the laboratory for a 1-hour visit. The participant will do another EEG while the caregiver fills out more surveys. The doctor will take the participant's vital signs and prescribe the medication. 3. The participant will be randomly assigned to take either methylphenidate HCl or amphetamines every morning for 3 weeks. At the end of each week, the caregiver and teacher will fill out a questionnaire about the participant's behaviors and symptoms, including side effects. 4. For one week, the participant will not take medications. They will come back into the lab for another EEG at the end of that week. 5. The participant will then take the other medication every morning for 3 weeks. At the end of each week, the caregiver and teacher will fill out a questionnaire about the participant's behaviors and symptoms, including side effects. 6. It will take participants about 7 weeks to complete this study. During this time, they will complete 3 in-person and 6 virtual study visits. 7. The research funds will cover cost associated with the study. The participant's health insurer will not be billed for the medications or treatment. Medications will be provided through the research pharmacy. 8. Participants will be given a report at the end of the study with details about the medication trials, symptom response, and any other findings. They will receive up to $270 for the completion of the study. Some travel-related costs will be covered by the study.

Подробное описание

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.

Вмешательства

• Препарат methylphenidate HCl
  3-week titration of liquid Quillivant XR
• Препарат Mixed amphetamine salts extended release
  3-week titration of liquid Dyanavel XR

Первичные конечные точки

• Medication A Clinical Global Impressions - Improvement Scale (CGI-I) [Срок оценки: Week 3 Virtual Visit (Day 22)]
• Medication B Clinical Global Impressions - Improvement Scale (CGI-I) [Срок оценки: End of Study Virtual Visit (Day 50)]
• Frontal Theta Beta Ratio [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]
• Aperiodic Dynamics [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]
• P100 Visual Evoked Potential Amplitude [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]
• Vanderbilt Rating Scales [Срок оценки: 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]

Вторичные конечные точки (5)

• P100 Visual Evoked Potential Habituation [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]
• Side Effects Rating Scale, Parent- and Teacher-Report [Срок оценки: 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 [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]
• N2 Event Related Potential Amplitude [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]
• P300 Event Related Potential Amplitude [Срок оценки: Eligibility Visit (Day 0), Baseline Visit (Day 1), Crossover Visit (Day 29)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Boston Children's Hospital at Two Brookline Place — Brookline

Идентификаторы

NCT: NCT07650643 · P00055002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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