Methylphenidate for ADHD

(AMPAIII Trial)

Recruiting at 1 trial location

Overseen By Steve W Wu, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Donald Gilbert, MD, MS, FAAN, FAAP

Must not be taking: Antidepressants, Non-stimulants, Dopamine blockers, Mood stabilizers

Disqualifiers: Autism, Epilepsy, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

214 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if two brain measurements can guide better treatment for children with ADHD. It tests how the brain reacts to methylphenidate, a common ADHD medication, using these measurements. The trial includes children aged 8 to 12 who either have ADHD or are typically developing. Participants will take a single dose of the medication and compare results with a placebo. Children with ADHD who often struggle with attention, impulsivity, and hyperactivity might be suitable candidates, especially if they currently use stimulant medications and can pause them for the study. As a Phase 4 trial, this research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

If your child is currently taking stimulant medications for ADHD, they will need to stop taking them as specified in the study procedures. However, if they are taking antidepressants, non-stimulant ADHD medications, or other listed medications, they cannot participate in the trial.

What is the safety track record for Methylphenidate?

Research has shown that methylphenidate is generally safe for children with ADHD. Studies have found that children tolerate it well, and it effectively manages ADHD symptoms. For instance, children taking methylphenidate experience fewer injuries than those not on the medication, suggesting it reduces risky behaviors linked to ADHD.

Most side effects are mild and temporary, such as trouble sleeping or reduced appetite. Monitoring long-term use, especially in very young children, is important to prevent potential issues.

Overall, evidence supports methylphenidate as a safe and effective option for managing ADHD in children. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Methylphenidate is unique because it targets dopamine and norepinephrine pathways in the brain, which are crucial for attention and impulse control. Unlike some treatments for ADHD that can take weeks to show effectiveness, methylphenidate often works quickly, sometimes within an hour, providing rapid symptom relief. Researchers are excited about this treatment because it offers a well-tolerated and effective option for managing ADHD symptoms in children, helping improve focus and behavior in a relatively short period.

What is the effectiveness track record for Methylphenidate in treating ADHD?

Research has shown that methylphenidate, which participants in this trial may receive, helps reduce the main symptoms of ADHD, such as trouble paying attention, acting impulsively, and being overly active. Studies find that it improves behavior in school and helps children focus and maintain control. Methylphenidate is a stimulant, meaning it boosts certain brain chemicals that aid attention and behavior. Evidence suggests it provides more symptom relief than non-stimulant medications. Overall, it is a well-known treatment for managing ADHD symptoms in children. ^{6 7 8 9 10}

Who Is on the Research Team?

Donald L Gilbert, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Stewart H Mostofsky, MD

Principal Investigator

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Are You a Good Fit for This Trial?

This trial is for right-handed children aged 8-12 years with ADHD, who are willing to suspend stimulant medications if prescribed. Healthy controls without ADHD or other disorders can also join. It excludes those on certain medications, with onset of menses, pregnancy, or serious neurological conditions.

Inclusion Criteria

I can understand and agree to the study's terms.

I am between 8 and 12 years old.

For children with ADHD prescribed stimulant medications, willing to suspend taking medications as specified in the study procedures

Exclusion Criteria

I have been diagnosed with a speech/language disorder or reading disability.

You have a device implanted in your body, such as a brain stimulator or pacemaker.

I am currently taking medication for depression, ADHD, or mood stabilization.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants complete diagnostic and psychoeducational testing, and parents complete standardized questionnaires and a psychiatric diagnostic interview

1 day

1 visit (in-person)

Treatment

Participants undergo pre-dose TMS, receive either MPH or placebo, and then undergo post-dose TMS

4 weeks

2 visits (in-person, 2-week intervals)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylphenidate
• Placebo

Trial Overview The study tests the effects of Methylphenidate (a common ADHD medication) against a placebo in improving brain function measures obtained by Transcranial Magnetic Stimulation (TMS). The goal is to refine treatment precision for ADHD in children.

How Is the Trial Designed?

Group I: Attention Deficit Hyperactivity Disorder (ADHD) Experimental Treatment 2 Interventions

8 to 12 year old children diagnosed with ADHD. Randomized, blinded, single dose, placebo controlled, crossover trial.

Group II: Typically developing controls (TDC) Active Control 1 Intervention

Typically developing controls - 8 to 12 year old children

Methylphenidate is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in Canada as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in European Union as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Who Is Running the Clinical Trial?

Donald Gilbert, MD, MS, FAAN, FAAP

Lead Sponsor

Trials

1

Recruited

210+

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Collaborator

Trials

93

Recruited

25,200+

Published Research Related to This Trial

In a study involving 308 patients aged 6-17 with ADHD, 65% showed significant improvement after 3 weeks of treatment with Metadate CD, indicating its effectiveness in real-world clinical practice.

The majority of patients (87%) reported satisfaction with Metadate CD, and those switching from other methylphenidate formulations found it to be as effective or better, with adverse events aligning with existing safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A postmarketing clinical experience study of Metadate CD. Dirksen, SJ., D'Imperio, JM., Birdsall, D., et al.[2019]

Controlled-delivery methylphenidate (methylphenidate CD) is effective and well tolerated for treating ADHD in children aged 6 and older, showing superior control of symptoms compared to osmotic release methylphenidate during a typical school day.

In clinical trials lasting 3 weeks, methylphenidate CD was found to be more effective than a placebo and equally effective as immediate-release methylphenidate, making it a strong option for managing ADHD symptoms during school hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review of its use in the treatment of children and adolescents with attention-deficit hyperactivity disorder. Anderson, VR., Keating, GM.[2018]

Dexmethylphenidate, a chirally pure form of methylphenidate, has been shown to effectively manage ADHD in children at half the dose of traditional Ritalin, based on clinical trials involving 684 children.

The drug works by inhibiting the reuptake of norepinephrine and dopamine, and has been found to be well tolerated, with ongoing research to further understand its therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride. [2018]

Controlled-delivery methylphenidate (methylphenidate CD) is effective and well-tolerated for treating ADHD in children aged 6 and older, showing superior control of symptoms compared to osmotic release methylphenidate during a typical school day.

In clinical trials lasting 3 weeks, methylphenidate CD was found to be more effective than a placebo and equally effective as immediate-release methylphenidate, making it a strong option for managing ADHD symptoms during school hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on methylphenidate controlled-delivery capsules (Equasym XL, Metadate CD) in the treatment of children and adolescents with attention-deficit hyperactivity disorder. Anderson, VR., Keating, GM.[2019]

A review of the French Pharmacovigilance database revealed 21 reported adverse drug reactions related to methylphenidate, with 16 cases suspected to be linked to the medication; these were mostly mild and resolved quickly.

The findings indicate that there is no evidence of methylphenidate misuse or overuse among the 1300 to 4000 children treated in France, supporting the need for continued strict prescription regulations to prevent potential misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Utilization of methylphenidate(Ritalin) in France]. Frances, C., Hoizey, G., Millart, H., et al.[2013]

In a study of 53 pediatric ADHD patients switched from OROS-MPH to Novo-MPH ER-C, 87% experienced destabilization of their condition, indicating that the two medications are not therapeutically equivalent despite being bioequivalent.

Patients switched to Novo-MPH ER-C reported a shorter duration of effect and different side effects compared to those who remained on OROS-MPH, suggesting that treatment disruptions can significantly impact ADHD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical impact of switching attention deficit hyperactivity disorder patients from OROS(®)-MPH to Novo-MPH ER-C(®): A paediatric practice review. van Stralen, JP.[2021]

In a 7-week study involving 226 adults with ADHD, OROS methylphenidate significantly improved ADHD symptoms compared to placebo, as shown by lower scores on the Adult ADHD Investigator Symptom Report Scale.

The treatment was well tolerated, with no serious adverse events reported, and a higher percentage of participants on OROS methylphenidate were classified as responders compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, double-blind, parallel group, dose-escalation study. Adler, LA., Zimmerman, B., Starr, HL., et al.[2022]

In a study of 28 children aged 6-12, lisdexamfetamine dimesylate (LDX) effectively reduced ADHD symptoms, but stimulant-naïve children experienced more severe treatment-emergent adverse events (TEAEs) like trouble sleeping and stomach pain compared to those with prior stimulant exposure.

The study suggests that previous exposure to stimulant medications may influence the type and severity of side effects experienced, highlighting the need for further research with larger samples to better understand these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in medication treatment-naïve children with attention-deficit/hyperactivity disorder: results from a small, controlled trial of lisdexamfetamine dimesylate. Wigal, SB., Wong, AA., Jun, A., et al.[2015]

In a study involving children aged 6-12 years with ADHD, once-daily modified-release methylphenidate (EqXL) was found to be non-inferior to twice-daily immediate-release methylphenidate (MPH-IR) in reducing ADHD symptoms over three weeks.

Both formulations of methylphenidate were significantly more effective than placebo, and all treatments were well tolerated, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder. Findling, RL., Quinn, D., Hatch, SJ., et al.[2018]

In a study involving 105 children and adolescents with ADHD, switching from immediate-release methylphenidate (MPH) to OROS MPH (a long-acting formulation) maintained and potentially improved ADHD symptom control over 21 days.

Approximately 75% of parents and investigators rated the OROS MPH therapy as good or excellent, indicating it was well tolerated and effective, particularly in managing symptoms during the after-school period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptom control in children and adolescents with attention-deficit/hyperactivity disorder on switching from immediate-release MPH to OROS MPH Results of a 3-week open-label study. Remschmidt, H., Hoare, P., Ettrich, C., et al.[2022]

Citations

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

Comparative efficacy and tolerability of medications for ... Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC524494/

Efficacy of two once-daily methylphenidate formulations ... A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4. ...

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

Evidence-based pharmacological treatment options for ... Investigating the potential therapeutic effect in ADHD, a pilot study and a first randomized controlled trial (as an add-on to methylphenidate treatment in 53 ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/jcpt.13486

“Real‐world” effectiveness of methylphenidate in improving ... Although some studies indicate that the short-term use of methylphenidate may improve outcomes in the school environment, the available evidence ...

5. psychiatrist.com psychiatrist.com/jcp/comparison-efficacy-medications-adult-attention-deficit-hyperactivity/

A Comparison of the Efficacy of Medications for Adult ... Although both stimulant and nonstimulant medications are effective for treating ADHD in adults, stimulant medications show greater efficacy for the short ...

6. 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 FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12443935/

Current insights into the safety and adverse effects of ... The cumulative evidence supports the use of MPH in ADHD, particularly given its potential for favorable neuropsychiatric outcomes. Nonetheless, ...

8. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30269-4/fulltext

Comparative efficacy and tolerability of medications for ... Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0149763419302350

Neurological and psychiatric adverse effects of long-term ... Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494554/

Methylphenidate for attention deficit hyperactivity disorder ... Similarly, ADHD drugs decreased injuries among 5‐ to 10‐year‐old children from 32% to 44%, when compared to ADHD children without treatment (Dalsgaard 2015a).