Predictors of Improvements in Irritability and Aggression in Children With ADHD Treated With CNS Stimulants

Part of paid clinical trials in Hershey, Pennsylvania.

Sponsor
Milton S. Hershey Medical Center
Study ID
NCT06871488
Phase
PHASE4
Status
Recruiting
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Conditions

  • ADHD - Attention Deficit Disorder With Hyperactivity
  • Aggression Childhood
  • Irritability

Eligibility Criteria

Sex
ALL
Age
7 Years - 12 Years
Healthy Volunteers
Not accepted

Interventions

  • CNS Stimulant — DRUG
    The second treatment phase (blinded within subjects crossover) will compare one week of the optimal dose of CNS Stimulant (from the prior phase) to one week of placebo for a total of 14 days of data collection.
  • Placebo — DRUG
    Placebo is only used during the second of two treatment phases. The second treatment phase (blinded within subjects crossover) will compare one week of the optimal dose of CNS Stimulant (from the prior phase) to one week of placebo.
  • CNS Stimulant open label first phase — OTHER
    The first treatment phase will optimize CNS stimulant dose under open label conditions using any approved FDA medication for pediatric ADHD at the FDA approved doses.

Study Details

Impulsive Aggression and chronic irritability (IACI) often occur together and are one of the most common reasons children present for behavioral health (BH) care. ADHD frequently associated with IACI as upwards of 50% of youth with ADHD manifest impairing IACI levels. IACI is the most common reason that children with ADHD are prescribed antipsychotics and admitted to inpatient BH units. Systematic dose optimization of CNS stimulants improves levels of IACI, reducing the need for these more intensive and burdensome treatments. However, response varies, with over half of children with ADHD showing meaningful improvement, upwards of 40% receiving minimal benefit and 3 to 10% exhibiting increased IACI levels. Symptom levels of ADHD or IACI and other demographic variables are of limited utility for predicting response, suggesting the need to move beyond symptoms in the search for treatment predictors. Youth with ADHD and IACI struggle with multiple aspects reinforcement learning (RL), defined as learning from interactions with the environment to reach a goal. Successful RL efforts tap multiple cognitive functions. In controlled laboratory tasks, youth with IACI and various BH disorders exhibit excessive behavioral and neural response to receiving reward (reward responsiveness), difficulty processing environmental cues to adapt behavior to meet a goal (set shifting/goal updating) and impaired ability to flexibly attend to relevant stimuli when blocked from a goal (frustrative nonreward). Event related potentials (ERP) are small electrical responses in the brain in response to specific events or stimuli measured by electroencephalogram (EEG) testing. ERPs exist that can serve as established neural measures of each of these cognitive functions offering a child friendly means to assess their contribution to observable levels of IACI. CNS stimulants improve functioning in these specific realms and impact associated ERPs to the degree that differences between ADHD and non-ADHD youth disappear. This study will examine the capacity of these ERPs to predict levels of IACI exhibited by children with ADHD when at home. Investigators will then assess if variability across children in the capacity of CNS stimulants to impact RL associated ERPs accounts for differences in the clinical effects of CNS stimulant medications to improve IACI at home using a multimethod battery integrating ERPs, parent report and task performance. Specifically, investigators will examine variance in the reward positivity (RewP) ERP when receiving reward feedback, the switch positivity (SwP) ERP measuring mental effort when cued to shift set and the change in P3b amplitude measuring attention allocation when transitioning from reward to nonreward on a go-no-go task. To achieve these aims, 136 children with ADHD and elevated IACI levels will have their CNS stimulant dose optimized over six weeks and then complete a two week within subjects crossover trial of placebo versus optimal dose. ERP collection will be completed within each blinded week. Parent ratings will be gathered 3 times per day including during peak and off-peak times of medication efficacy to capture the variance in IACI levels within the day and disentangle reports of worsening IACI related to loss of previously beneficial medication effects versus those most likely related to a direct adverse response to medication.

Key Dates

Start date
Mar 5, 2026
Status verified
Apr 2026
Primary completion
Feb 28, 2030
Completion
Jun 30, 2030

Study Design

Enrollment
136 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Active Comparator: Blinded optimal dose (phase two)
    In this second treatment phase of the study, all participants will receive under blinded conditions their optimal dose of CNS stimulant from the prior phase for a total of 7 days
  • Placebo Comparator: Placebo (phase two)
    In this second treatment phase of the study, all participants will receive placebo under blinded conditions for a total of 7 days
  • Experimental: open label dose optimization (phase one)
    In this first treatment phase, all participants will have their dose of CNS Stimulant optimized over 6 visits under open label conditions. This arm will use any FDA approved CNS stimulant for pediatric ADHD at their approved dose. By the end of this phase, the optimal dose for the next phase will be identified.

Primary Outcome Measure

RCT phase: Guardian rated Affective reactivity Index (ARI) [ Time Frame: 7 days on med and for 7 days on placebo for 14 days of data collection ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Penn State Health Dept of PsychiatryHersheyPennsylvania17033-

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Penn State Health Dept of Psychiatry· Hershey, PA

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