CNS Stimulants for ADHD

Overseen By James G Waxmonsky, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Milton S. Hershey Medical Center

Must be taking: CNS stimulants

Must not be taking: Antipsychotics, Mood stabilizers, Benzodiazepines

Disqualifiers: Autism, Bipolar, Intellectual delay, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well CNS stimulant medications (drugs that increase brain activity) assist children with ADHD who experience high levels of irritability and aggression at home. Researchers will examine how these medications influence brain responses related to learning and attention, using methods like EEG (a test that records brain activity). The trial seeks to identify which children benefit most from the medications by testing different doses and a placebo. Children who frequently experience irritability or aggression due to ADHD and whose parents are open to CNS stimulant treatment might be suitable for this study. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that participants stop taking antipsychotics, mood stabilizers, and other medications that affect EEG data collection, like benzodiazepines.

What is the safety track record for CNS stimulants?

Research has shown that medications called CNS stimulants, often used to treat ADHD, are generally safe. In past studies, many people taking these medications experienced at least one side effect, but most found them manageable. Common side effects include trouble sleeping or reduced appetite.

Importantly, studies have found no increased risk of serious heart problems in children and young people taking ADHD medications, including CNS stimulants. For most kids, these medications are unlikely to cause severe heart issues. Additionally, medications like methylphenidate, a type of CNS stimulant, have been safely used in children for up to two years. Regular check-ups are recommended to monitor any side effects over time.

Overall, CNS stimulants are usually well-tolerated, and while side effects can occur, they are typically not severe. For those considering joining a trial, it is reassuring to know that these medications are already approved by the FDA for treating ADHD, providing an additional layer of safety assurance. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using CNS stimulants for ADHD because these medications can be precisely optimized for each individual, potentially leading to more effective and individualized treatment plans. Unlike traditional treatments that might not account for individual differences in drug metabolism and response, this approach involves a personalized dose optimization phase before a blinded treatment period. This means that every participant receives their tailored optimal dose, which could mean fewer side effects and better symptom control compared to standard ADHD medications that follow a one-size-fits-all approach.

What evidence suggests that CNS stimulants could be effective for ADHD with impulsive aggression and chronic irritability?

Research has shown that medications called CNS stimulants can help reduce ADHD symptoms in children, with up to 90% of kids showing improvement. This trial will involve two phases: an open-label dose optimization phase and a blinded phase. In the first phase, participants will have their dose of a CNS stimulant optimized. In the second phase, participants will receive either their optimal dose of CNS stimulant or a placebo under blinded conditions. One study found that drugs like amphetamines and methylphenidate improved quality of life more than a placebo. These stimulants help by boosting brain functions that are often weaker in ADHD, such as attention and self-control. While results can vary, stimulants have reduced impulsive aggression and irritability, which are common in ADHD. Most children benefit from these treatments, but some may see little improvement or even an increase in symptoms. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children with ADHD who show signs of impulsive aggression and chronic irritability. Participants must have elevated levels of these behaviors and will undergo a process to find the best dose of CNS stimulants over six weeks, followed by a two-week test comparing their optimized dose with a placebo.

Inclusion Criteria

Meet criteria for any presentation of ADHD

Moderate or worse impairment related to ADHD

Elevated levels of irritability and/or aggression on guardian ratings of Affective Reactivity Index and Retrospective Modified Overt Aggression Scale

Exclusion Criteria

Autism Spectrum Disorder

Bipolar Disorder

Intellectual/Developmental Delay

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Open-label Dose Optimization

Participants have their CNS stimulant dose optimized over 6 visits under open label conditions.

6 weeks

6 visits (in-person or virtual)

Randomized Controlled Trial (RCT)

Participants undergo a 2-week within-subjects crossover trial of optimal dose versus placebo.

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CNS Stimulant

Trial Overview The study tests if brain responses (ERPs) can predict how well CNS stimulant medications help reduce aggression and irritability in kids with ADHD at home. It involves optimizing medication dosage, then comparing effects on behavior when taking the drug versus a placebo.

How Is the Trial Designed?

Group I: open label dose optimization (phase one) Experimental Treatment 1 Intervention

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.

Group II: Blinded optimal dose (phase two) Active Control 1 Intervention

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

Group III: Placebo (phase two) Placebo Group 1 Intervention

In this second treatment phase of the study, all participants will receive placebo under blinded conditions for a total of 7 days

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6109107/

Comparative efficacy and tolerability of medications for ... Medications for ADHD were less efficacious and less well tolerated in adults than in children and adolescents.

2. sciencedirect.com sciencedirect.com/science/article/pii/S016372582100142X

Evidence-based pharmacological treatment options for ... Overall positive results regarding efficacy and tolerability, comparable to approved stimulants, have been reported from a phase II study in n = 85 adults with ...

3. jaacap.org jaacap.org/article/S0890-8567(24)00304-6/fulltext

Systematic Review and Meta-Analysis: Effects of ... The analysis showed that medications such as amphetamines, methylphenidate, and atomoxetine improved QoL compared to placebo, with moderate ...

4. acamh.onlinelibrary.wiley.com acamh.onlinelibrary.wiley.com/doi/10.1002/jcv2.12146

Efficacy of stimulants for preschool attention‐deficit ... Our findings demonstrated that stimulants are effective in reducing ADHD symptoms among preschoolers (standardized mean difference = −0.59; 95% ...

5. ramp.luriechildrens.org ramp.luriechildrens.org/en/conditions-and-treatments/medications/stimulants/

Stimulants for Children with ADHD Up to 90% of patients will have ADHD symptom improvement on one of the stimulants. Response may vary across domains impacted by ADHD symptoms. Patients may see ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1110212

ADHD Drugs and Serious Cardiovascular Events in ... This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10601982/

Adverse Effects of Stimulant Interventions for Attention Deficit ... The data revealed that more than half of the patients experienced at least one side effect; however, most patients reported that intervention ...

8. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-medications-used-treat-attention

Safety Review Update of Medications used to treat ADHD Study findings reported no evidence of increased risk of serious cardiovascular effects among children and young people who use ADHD medications.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2215036623000421

Long-term safety of methylphenidate in children and ... Methylphenidate used for the treatment of child and adolescent ADHD for up to 2 years is safe. However, recommended follow-up examinations should be performed ...

10. cms.gov cms.gov/medicare-medicaid-coordination/fraud-prevention/medicaid-integrity-education/pharmacy-education-materials/downloads/stim-pediatric-factsheet11-14.pdf

Stimulant and Related Medications: Use in Pediatric Patients Stimulant and related medications are FDA approved for the treatment of ADHD, narcolepsy, and exogenous obesity (a body mass index [BMI] at or above the 95th ...