Methylphenidate for Epilepsy-Related Cognitive Deficits

Recruiting at 7 trial locations

Overseen By Marissa Kellogg, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: MAOIs, Erectile dysfunction meds

Disqualifiers: Psychotic disorders, Severe anxiety, Bipolar, others

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: 24

226 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether methylphenidate, a medication typically used for ADHD, can assist with memory and thinking challenges in adults with epilepsy. Participants will randomly receive either methylphenidate or a placebo (a sugar pill) for eight weeks, with attention and memory tested before and after. Individuals with epilepsy who experience memory and thinking problems affecting daily life might be suitable for this trial. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that your anti-seizure medications remain unchanged during the study unless there's a significant change in your condition. If you are taking certain medications like monoamine oxidase inhibitors (MAOIs) or medications that lower the seizure threshold, you may need to stop them before joining the trial.

What is the safety track record for methylphenidate?

Research has shown that methylphenidate (MPH) is generally safe for people with epilepsy, particularly concerning seizure frequency. Large studies have found that MPH does not significantly increase seizures in children with both ADHD and epilepsy. In one study involving 35 adults with epilepsy, MPH improved thinking skills at doses of 10 mg and 20 mg. These findings suggest that MPH is well-tolerated and safe for people with epilepsy. Since the FDA has already approved MPH for ADHD, this further supports its safety for other conditions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for epilepsy-related cognitive deficits, which often involve antiepileptic drugs to control seizures, methylphenidate is unique because it targets cognitive enhancement directly. Methylphenidate, commonly known for its use in ADHD, works by increasing dopamine levels in the brain, potentially improving attention and memory. Researchers are excited about its use in epilepsy because it could address cognitive issues without directly altering seizure activity, offering a new pathway for enhancing brain function in these patients.

What evidence suggests that methylphenidate might be an effective treatment for epilepsy-related cognitive deficits?

Research shows that methylphenidate (MPH), commonly used for ADHD, might enhance attention and memory in people with epilepsy. In this trial, some participants will receive MPH, while others will receive a placebo. Studies have found that people with epilepsy who struggle with cognitive skills perform better on attention and memory tests when taking MPH compared to a placebo. For instance, patients scored higher on various cognitive tests, such as the Symbol Digit Modalities Test (SDMT). MPH has also been linked to faster information processing. These findings suggest that MPH could alleviate cognitive issues related to epilepsy. ^{1 2 3 5 6}

Who Is on the Research Team?

Beth A Leeman-Markowski, MD

Principal Investigator

VA NY Harbor Healthcare System, New York, NY

Are You a Good Fit for This Trial?

Adults over 18 with focal-onset epilepsy and self-reported cognitive issues can join this trial. They must be able to consent, live independently, speak English fluently, and have a stable seizure frequency without expected medication changes. Excluded are those with severe anxiety or impulse control disorders, untreated sleep disorders, major illnesses like cancer requiring active treatment, history of stroke or TIA (transient ischemic attack), psychotic disorders, recent neurosurgery or seizures close to testing times.

Inclusion Criteria

I am healthy, live independently, and can manage my daily activities.

I can take care of myself and do my daily activities on my own.

Healthy controls with fluency in written and spoken English

Exclusion Criteria

I have epilepsy and have never had a stroke or a transient ischemic attack.

I have epilepsy and haven't recently used sedating medications.

I do not have epilepsy or non-epileptic seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either methylphenidate or placebo for 8 weeks. Dosage of MPH is titrated to 20mg twice daily.

8 weeks

Baseline, Week 8

Open-label Extension

All participants receive open-label methylphenidate for 8 weeks. Dosage is titrated to 20mg twice daily.

8 weeks

Week 16

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 is testing if Methylphenidate (MPH), known for treating ADHD, can also help adults with epilepsy improve memory and thinking problems. Participants will either receive MPH or a placebo without knowing which one they're taking. Their attention and memory will be tested before starting the pills at Week 8 and again at Week 16 after everyone has had the chance to take MPH.

How Is the Trial Designed?

Group I: Open-Label Methylphenidate Experimental Treatment 1 Intervention

All subjects will be offered open-label methylphenidate during Weeks 9-16. the dosage of MPH will begin at 10mg twice per day, at 8am and 12pm, for one week. The dosage will then increase to 20mg twice daily, at 8am and 12pm, for the next 7 weeks.

Group II: Methylphenidate Experimental Treatment 1 Intervention

Subjects who will receive methylphenidate in the double-blinded period; when assigned to the active drug, the dosage of MPH will begin at 10mg twice per day, at 8am and 12pm, for one week. The dosage will then increase to 20mg twice daily, at 8am and 12pm, for the next 7 weeks.

Group III: Placebo Placebo Group 1 Intervention

Subjects who will receive placebo in the double-blinded period; when assigned to receive the placebo during the double-blinded period, subjects will be given a sugar pill for 8 weeks. The sugar pill will be taken twice per day, at 8am and 12pm.

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Portland VA Medical Center

Collaborator

Trials

44

Recruited

7,800+

Miami VA Healthcare System

Collaborator

Trials

18

Recruited

2,400+

VA Boston Healthcare System

Collaborator

Trials

73

Recruited

971,000+

VA New York Harbor Healthcare System

Collaborator

Trials

25

Recruited

14,400+

Published Research Related to This Trial

Methylphenidate (MPH) has demonstrated high response rates in treating ADHD in children with epilepsy without increasing seizure frequency, although the studies reviewed had limitations such as small sample sizes and short observation periods.

There is a need for further research on the long-term effects of MPH and its use in children with frequent seizures, while other medications like amphetamines and atomoxetine show promise and warrant further randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attention-deficit/hyperactivity disorder in pediatric patients with epilepsy: review of pharmacological treatment. Torres, AR., Whitney, J., Gonzalez-Heydrich, J.[2022]

In a 3-month study involving 11 adult epilepsy patients, the addition of methylphenidate (MPH) to their antiepileptic drug regimens led to significant improvements in quality of life and cognitive function, as measured by the QOLIE-89 and Microcog assessments.

Importantly, MPH did not significantly alter seizure control, with most patients maintaining their seizure status throughout the study, and no serious adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Evaluation of the Effects of Methylphenidate on Outcomes in Adult Epilepsy Patients. Moore, JL., McAuley, JW., Long, L., et al.[2022]

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]

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]

Methylphenidate is identified as the most suitable medication for treating ADHD in children with epilepsy, showing a limited risk of worsening seizures based on available studies.

Effective management of ADHD in these children should include not only pharmacological treatment but also optimal antiepileptic drug therapy, addressing psychiatric comorbidities, and providing school support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of attention-deficit/hyperactivity disorder in children and adolescents with epilepsy. Auvin, S.[2019]

In a 1-month open-label trial involving 30 adults with epilepsy, methylphenidate significantly improved cognitive functions, as measured by tests like the Symbol-Digit Modalities Test and Medical College of Georgia Memory Test, without increasing seizure frequency.

The study suggests that methylphenidate is a safe option for enhancing cognition and quality of life in adults with epilepsy, warranting further investigation through larger, controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate, cognition, and epilepsy: A 1-month open-label trial. Adams, J., Alipio-Jocson, V., Inoyama, K., et al.[2018]

In a four-week trial involving 119 Korean children with ADHD, Concerta (OROS methylphenidate) was found to be well tolerated and effective in improving attention, behavior, and cognitive function as reported by parents, teachers, and investigators.

The study demonstrated significant improvements in cognitive performance through various tests, supporting the use of Concerta as a beneficial once-daily treatment option for children with ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of OROS methylphenidate in Korean children with attention-deficit/hyperactivity disorder. Lee, SI., Hong, SD., Kim, SY., et al.[2013]

A study involving 35 adults with epilepsy found that immediate-release methylphenidate (MPH) significantly improved cognitive performance at both 10 mg and 20 mg doses, indicating its potential efficacy for cognitive deficits in epilepsy.

No seizures were reported as a result of MPH treatment, and while some participants experienced mild adverse effects, the overall safety profile suggests that MPH could be a viable option for managing cognitive issues in epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study. Adams, J., Alipio-Jocson, V., Inoyama, K., 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]

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 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]

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Methylphenidate for Epilepsy-Related Cognitive Deficits

Trial Overview The study is testing if Methylphenidate (MPH), known for treating ADHD, can also help adults with epilepsy improve memory and thinking problems.

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The preponderance of evidence suggests that stimulants other than bupropion are safe and effective in the treatment of attention deficit disorder in children ...