Methylphenidate for Epilepsy-Related Cognitive Deficits

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Beth A Leeman-Markowski, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Methylphenidate (MPH) is a stimulant, FDA-approved for the treatment of attention deficit hyperactivity disorder (ADHD). It is unknown, however, if stimulants would be of benefit for memory and thinking problems due to epilepsy. In this study, participants will be assigned randomly (i.e., by flip of a coin), to a group that takes MPH and a group that takes a placebo (sugar pill). Participants will not know the group to which they have been assigned. Tests of attention and memory will be completed before taking the study pills and at Week 8. All participants will then have the option of taking MPH for the next two months, and attention and memory will be tested again at Week 16. The study will determine whether methylphenidate is helpful for the treatment of attention and memory problems in adults with epilepsy, and whether the medication is safe and beneficial when taken over an extended time period.

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 data supports the effectiveness of the drug Methylphenidate for epilepsy-related cognitive deficits?

Research shows that Methylphenidate, commonly used for ADHD, can improve attention and cognitive function. In a study with epilepsy patients, Methylphenidate was added to their existing medication and showed potential benefits in cognition without serious side effects. ^{1 2 3 4 5}

Is methylphenidate generally safe for humans?

Methylphenidate, used in various forms like Concerta and Ritalin, has been studied for safety in both children and adults with ADHD. Most studies report that it is generally well-tolerated, with mild side effects that usually resolve quickly. However, long-term effects are still being studied, and it is prescribed under strict regulations in some countries to prevent misuse. ^{4 6 7 8 9}

How is the drug methylphenidate unique for treating cognitive deficits in epilepsy?

Methylphenidate is unique for treating cognitive deficits in epilepsy because it is primarily used for ADHD and has shown potential to improve cognition in adults with epilepsy, a condition with no well-validated treatments for cognitive issues. It is being explored for its ability to enhance cognitive function without increasing seizure risk, which is a novel approach compared to traditional antiepileptic drugs that focus mainly on reducing seizures. ^{1 2 10 11 12}

Research Team

Beth A Leeman-Markowski, MD

Principal Investigator

VA NY Harbor Healthcare System, New York, NY

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Methylphenidate (Stimulant)
• Placebo (Other)

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.

Participant Groups

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 Canada for the following indications:

Approved in Canada 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+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

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+

Findings from Research

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 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 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]

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 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

An Evaluation of the Effects of Methylphenidate on Outcomes in Adult Epilepsy Patients. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of OROS methylphenidate in Korean children with attention-deficit/hyperactivity disorder. [2013]

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

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

6. 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]

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. 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]

9. France pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

Attention-deficit/hyperactivity disorder in pediatric patients with epilepsy: review of pharmacological treatment. [2022]

11. France pubmed.ncbi.nlm.nih.gov

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

12. United States pubmed.ncbi.nlm.nih.gov

Methylphenidate, cognition, and epilepsy: A 1-month open-label trial. [2018]