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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 4INTERVENTIONAL

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits: a Randomized, Double-blind, Placebo-controlled Trial

Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits (NCT04419272) is a Phase 4 interventional studying Epilepsy, sponsored by VA Office of Research and Development. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About 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.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 226 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Epilepsy subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. SUBJECTS WITH EPILEPSY Participants will include adult subjects with focal-onset epilepsy, based on clinical history, imaging studies and ictal and/or interictal EEG interpreted by a clinical epileptologist. Seizures may be symptomatic, idiopathic, traumatic, or non- traumatic in etiology. Subjects must have self-reported cognitive dysfunction. Subjects must also meet the following eligibility criteria: - Age 18 years of age or older; - Capacity to provide willing to sign a consent form; - Ability to live independently and complete activities of daily living; - Stable seizure frequency at the time of enrollment, such that the subject's treating physician does not believe a change in ASM regimen to be warranted during the trial (ASMs should remain unchanged during the 16 weeks of participation unless absolutely required clinically due an unanticipated change in seizure frequency or severity); - Fluency in written and spoken English. 2. CONTROLS \*DO NOT UNDERGO ANY DRUG OR PLACEBO INTERVENTION Two additional subject groups will be included, to control for effects of repeated testing in the open-label extension phase: healthy subjects and epilepsy patients without cognitive complaints, who will not receive the study drug at any point during the study. Epilepsy patients without cognitive deficits must otherwise meet all of the above criteria. Healthy controls must meet the following Who May Qualify: - Age 18 years or older; - Capacity to provide willing to sign a consent form; - Ability to live independently and complete activities of daily living; - Fluency in written and spoken English. Who Should NOT Join This Trial: SUBJECTS WITH EPILEPSY Subjects with epilepsy with or without cognitive complaints will be excluded from participation for: - Psychogenic, non-epileptic spells - Delirium in the past year ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. SUBJECTS WITH EPILEPSY Participants will include adult subjects with focal-onset epilepsy, based on clinical history, imaging studies and ictal and/or interictal EEG interpreted by a clinical epileptologist. Seizures may be symptomatic, idiopathic, traumatic, or non- traumatic in etiology. Subjects must have self-reported cognitive dysfunction. Subjects must also meet the following eligibility criteria: * Age 18 years of age or older; * Capacity to provide informed consent; * Ability to live independently and complete activities of daily living; * Stable seizure frequency at the time of enrollment, such that the subject's treating physician does not believe a change in ASM regimen to be warranted during the trial (ASMs should remain unchanged during the 16 weeks of participation unless absolutely required clinically due an unanticipated change in seizure frequency or severity); * Fluency in written and spoken English. 2. CONTROLS \*DO NOT UNDERGO ANY DRUG OR PLACEBO INTERVENTION Two additional subject groups will be included, to control for effects of repeated testing in the open-label extension phase: healthy subjects and epilepsy patients without cognitive complaints, who will not receive the study drug at any point during the study. Epilepsy patients without cognitive deficits must otherwise meet all of the above criteria. Healthy controls must meet the following inclusion criteria: * Age 18 years or older; * Capacity to provide informed consent; * Ability to live independently and complete activities of daily living; * Fluency in written and spoken English. Exclusion Criteria: SUBJECTS WITH EPILEPSY Subjects with epilepsy with or without cognitive complaints will be excluded from participation for: * Psychogenic, non-epileptic spells * Delirium in the past year * Other progressive neurologic illness (i.e., malignant brain tumor). A benign, stable neoplasm with no plans for resection will not be cause for exclusion. * A history of alcohol or illicit drug abuse; * Generalized tonic-clonic or other generalized motor seizure(s) within 48 hours or focal-onset seizures with impaired awareness within 24 hours of neuropsychological testing; * Status epilepticus in the past year; * Neurosurgery within the past 6 months; * Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the last 2 years, more than 1 lifetime suicide attempt, and/or current high-risk suicide flag in the medical record; * Psychotic disorders * Severe anxiety (\>26 on the Beck Anxiety Inventory \[BAI\]) and impulse control disorders; * Untreated sleep disorders; * Use of narcotic or other sedating medications within 6 hours of testing (i.e., diphenhydramine); * Concurrent severe major medical illness (i.e., cancer requiring chemotherapy or resection) * Prior transient ischemic attack (TIA) or stroke Subjects with epilepsy will also be excluded for a diagnosis of dementia (i.e., Alzheimer's disease). Subjects with epilepsy and cognitive complaints must have a MoCA score of 18 or greater. Subjects with epilepsy and no cognitive complaints must have a MoCA score of 26 or greater. Subjects with epilepsy and cognitive complaints must meet additional exclusion criteria, to minimize risks of MPH: * Current pregnancy or pregnancy planned during the trial * Breastfeeding * Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or MAOI use within 14 days of beginning the trial; * Structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, or coronary artery disease (including a history of myocardial infarction, cardiac stent placement, coronary artery bypass graft surgery, or angina); * Bipolar disorders; * Concurrent use of medications for erectile dysfunction (e.g., tadalafil, sildenafil); * Use of medications that may lower seizure threshold (e.g., tramadol, bupropion) or induce psychosis (i.e., varenicline); * Known allergy or intolerance to MPH; * Uncontrolled hypertension; HEALTHY CONTROLS Healthy controls will be excluded based on the following criteria: * History of seizures, epilepsy, or psychogenic, non-epileptic spells; * Diagnosis of dementia (i.e., Alzheimer's disease), MoCA score of \<26; * Delirium in the past year; * Other progressive neurologic illness (i.e., malignant brain tumor); * Prior moderate or severe traumatic brain injury (TBI); * Mild TBI within the past 6 months; * A history of alcohol or illicit drug abuse; * Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the last 2 years, more than 1 lifetime suicide attempt, and/or current high-risk suicide flag in the medical record; * Psychotic, severe anxiety (BAI \>26), or impulse control disorders; * Untreated sleep disorders; * Use of narcotic or other sedating medications within 6 hours of testing; * Ongoing major neurological or medical illness (i.e., cancer requiring chemotherapy or resection); * Prior TIA or stroke;

Treatments Being Tested

DRUG

Methylphenidate

10mg twice per day, at 8am and 12pm, for one week, then increased to 20mg twice daily, at 8am and 12pm, for the next 7 weeks during the double-blinded period.

OTHER

Placebo

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.

DRUG

Methylphenidate

During the open-label extension phase, dosing 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.

Locations (4)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Miami VA Healthcare System, Miami, FL
Miami, Florida, United States
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, United States
VA NY Harbor Healthcare System, New York, NY
New York, New York, United States
VA Portland Health Care System, Portland, OR
Portland, Oregon, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04419272), the sponsor (VA Office of Research and Development), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04419272 clinical trial studying?

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 … The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04419272?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04419272?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04419272. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04419272. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.