Biomarkers of ADHD Treatment Response

NCT ID: NCT05650775

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-17

Study Completion Date

2024-03-30

Brief Summary

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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. Do children with ADHD who show symptom reduction with methylphenidate have different EEG profiles than children who do not respond well to methylphenidate?
2. 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

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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

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ADHD

Keywords

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Electroencephalography ADHD Event related potentials Stimulants

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Methylphenidate Trial

3-week methylphenidate trial with weekly dose adjustments.

Group Type ACTIVE_COMPARATOR

Concerta

Intervention Type DRUG

3-week trial of oral methylphenidate extended release

Mixed Amphetamine Salts Trial

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

Group Type ACTIVE_COMPARATOR

Adderall-XR

Intervention Type 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.

Interventions

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Concerta

3-week trial of oral methylphenidate extended release

Intervention Type DRUG

Adderall-XR

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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).
Minimum Eligible Age

7 Years

Maximum Eligible Age

11 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Anne Arnett

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anne B Arnett, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Eugenia Chan, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

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2 Brookline Place

Brookline, Massachusetts, United States

Site Status

Countries

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United States

Other Identifiers

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ArnettChanTNC2022

Identifier Type: -

Identifier Source: org_study_id