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

Trial Summary

What is the purpose of this trial?

This trial is investigating how genetic differences in an enzyme called CES1 affect the way ADHD patients respond to the medication methylphenidate. The goal is to understand why some patients do not respond well or experience severe side effects. Methylphenidate (MPH) is a well-established treatment for ADHD, but not all patients respond to it, and some experience adverse reactions.

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 data supports the effectiveness of the drug Methylphenidate for ADHD?

Research shows that Methylphenidate, including its controlled-delivery forms like Metadate CD, is effective in reducing ADHD symptoms in children and adolescents. It has been found to be superior to placebo and comparable to immediate-release versions, providing better symptom control during the school day. ^{1 2 3 4 5}

Is methylphenidate generally safe for humans?

Methylphenidate, used in various forms like Ritalin and Concerta, is generally well tolerated in both children and adults with ADHD. Most reported side effects are mild and resolve quickly, but long-term effects are still being studied. ^{1 6 7 8 9}

How is the drug Methylphenidate unique for treating ADHD?

Methylphenidate, especially in its controlled-delivery form, is unique because it provides effective symptom control throughout the school day with just one dose, making it convenient for children and adolescents with ADHD. It is also available in a chirally pure form called dexmethylphenidate, which is effective at half the dose of regular Ritalin, potentially reducing side effects and drug interactions. ^{1 3 4 7 10}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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 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 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]

References

1. Switzerland 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. [2018]

2. Germany 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. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. New Zealand 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. [2019]

5. Germany 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A postmarketing clinical experience study of Metadate CD. [2019]

7. United States 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. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Utilization of methylphenidate(Ritalin) in France]. [2013]

9. United States 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. [2015]

10. England 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. [2021]