Methylphenidate for ADHD

Recruiting at 1 trial location

Overseen By Jeffrey Newcorn, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: Methylphenidate

Disqualifiers: Non-ADHD, Smokers, Pregnant, 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: Unknown

Duration: 8 hours per session

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the stimulant medication methylphenidate works for children and teens with ADHD and examines how genetic differences might affect its effectiveness. Researchers aim to determine if certain genetic profiles influence the medication's efficacy and how the body processes it. The trial targets children and teens aged 6 to 17 years who have been diagnosed with ADHD. Participants should be in good health, non-smokers, and interested in trying this treatment. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for methylphenidate?

Research has shown that methylphenidate (MPH) is generally safe for treating ADHD. Studies indicate that children and teenagers usually tolerate it well. The most common side effects include trouble sleeping and reduced appetite, but these are typically mild.

A thorough review highlights MPH's positive effects, especially for mental health. Another study confirmed its safety for long-term use, finding no major brain or mental health issues after more than a year of treatment.

Overall, methylphenidate is considered an effective and safe choice for managing ADHD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Methylphenidate is unique because it offers a well-established option for treating ADHD by directly targeting neurotransmitter activity in the brain, specifically dopamine and norepinephrine, to improve focus and control impulses. Researchers are excited about this treatment because it has a long history of safety and effectiveness, providing fast-acting relief for many patients. Unlike some other ADHD medications, methylphenidate's effects can be observed quickly, often within an hour, making it a reliable choice for managing symptoms throughout the day.

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

Research has shown that methylphenidate, the treatment under study in this trial, effectively treats ADHD. Studies have found that this medication significantly reduces key symptoms of ADHD, such as difficulty paying attention and hyperactivity, as reported by teachers and doctors. Methylphenidate, a stimulant, generally proves more effective for ADHD than non-stimulant medications. One study found that this medication improves behavior and focus in school, particularly in the morning. Overall, methylphenidate has successfully managed ADHD symptoms in both children and adults. ^{6 7 8 9 10}

Who Is on the Research Team?

Jeffrey Newcorn, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Mark Stein, PhD

Principal Investigator

University of Washington

Tanya Froehlich, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for young people aged 6-26 with a primary diagnosis of ADHD. It's open to those who have previously been part of MPH trials and are invited back for further study. Smokers, pregnant individuals, or those not considered healthy enough for MPH treatment by their doctors cannot participate.

Inclusion Criteria

I am between 6 and 26 years old and have been diagnosed with ADHD.

For former participants of MPH trials to be invited back for PK procedures.

Exclusion Criteria

You were not diagnosed with ADHD as your main condition.

I am not a candidate for medication treatment with MPH for my ADHD, as decided by my doctors.

You currently smoke or are pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive methylphenidate and are monitored for pharmacokinetics and pharmacodynamics in relation to CES1 genetic variants

8 hours per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylphenidate

Trial Overview The trial is examining how genetic differences in an enzyme called CES1 affect the body's response to Methylphenidate (MPH), a common medication used to treat ADHD. The goal is to understand the link between CES1 gene variants and MPH effectiveness.

How Is the Trial Designed?

Group I: Methylphenidate Experimental Treatment 1 Intervention

Youth with ADHD

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?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 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]

Citations

1. 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. ...

2. 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 ...

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

Evidence-based pharmacological treatment options for ... Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: Acute comparison and differential response.

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 ... We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8455398/

Methylphenidate for attention-deficit/hyperactivity disorder in ... There is substantial body of evidence to suggest that MPH is an effective and safe treatment option for adults with ADHD.