Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits

• Status: Not yet recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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, at Week 4, 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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: VA New York Harbor Healthcare System
• Collaborators: Miami VA Healthcare System; Portland VA Medical Center
• Treatments: Methylphenidate

Criteria

1. SUBJECTS WITH EPILEPSY Participants will include subjects with epilepsy, based on clinical history, imaging studies and ictal and/or interictal EEG interpreted by a clinical epileptologist. Seizures may be either symptomatic or idiopathic, primary generalized or focal-onset, and traumatic or non-traumatic in etiology. Subjects must have self-reported cognitive dysfunction.

Subjects must meet the following eligibility criteria:

• Age > or = 18 years old;

• IQ > or = 70, estimated by the Wechsler Test of Adult Reading (WTAR);

• 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 anticonvulsant regimen to be warranted during the trial (the anticonvulsant drugs should remain unchanged during the 16 weeks of participation unless absolutely required clinically due an unanticipated change in seizure frequency or severity);

• Fluency in English.

Exclusion criteria

• Psychogenic, non-epileptic spells;

• Diagnosis of dementia (i.e., Alzheimer's disease);

• Other progressive neurologic illness (i.e., malignant brain tumor). A benign, stable neoplasm with no plans for resection will not be cause for exclusion;

• Alcohol or illicit drug abuse within the past year, as this may affect cognition by other mechanisms. This information may be obtained by self-report, from the referring physician or by medical record. Subjects will also undergo urine drug testing at the baseline visit. Chronic, stable use of marijuana will not be cause for exclusion. In cases of intermittent, recreational use, it will be required that subjects refrain from marijuana for 2 weeks prior to testing. Cannabidiol use will be permitted.

• 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. This restriction will avoid testing during a post-ictal state. This timing is conservative, based on practice as well as prior studies of post-ictal cognitive function demonstrating return to baseline within one day (Dodrill and Ojemann, 2007; Helmstaedter, Elger, & Lendt, 1994).

• Prior status epilepticus in the past year;

• Neurosurgery within the past 6 months, as there may be recovery in cognition post-operatively;

• Current pregnancy or pregnancy planned during the trial;

• Breastfeeding;

• Concurrent treatment with a monoamine oxidase inhibitor (MAOI; e.g., selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue), or use of an MAOI within 14 days of beginning the trial (due to the risk of hypertensive crisis);

• Structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, or coronary artery disease, as complications due to small MPH-related increases in heart rate and blood pressure may be of concern in these populations;

• History of a suicide attempt in the past year;

• Psychotic or bipolar disorders, due to the risk of psychotic or manic symptom exacerbation;

• Concurrent use of medications for erectile dysfunction (e.g., tadalafil, sildenafil), due to an increased risk of priapism;

• Use of medications that may lower seizure threshold (e.g., tramadol, immediate release bupropion);

• Known allergy to methylphenidate;

• Use of narcotic or other sedating medications within 6 hours of testing (i.e., diphenhydramine), which may interfere with cognition;

• Uncontrolled hypertension;

• Concurrent severe major medical illness (e.g., cancer requiring chemotherapy or resection).

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 complaints must otherwise meet all of the above inclusion criteria, and will be excluded for the following:

• Psychogenic, non-epileptic spells;

• Diagnosis of dementia (i.e., Alzheimer's disease);

• Other progressive neurologic illness (i.e., malignant brain tumor). A benign, stable neoplasm with no plans for resection will not be cause for exclusion;

• Alcohol or illicit drug abuse within the past year. This information may be obtained by self-report, from the referring physician or by medical record. Subjects will also undergo urine drug testing at the baseline visit. Chronic, stable use of marijuana will not be cause for exclusion. In cases of intermittent, recreational use, it will be required that subjects refrain from marijuana for 2 weeks prior to testing. Cannabidiol use will be permitted.

• 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.

• Prior status epilepticus in the past year;

• Neurosurgery within the past 6 months;

• History of a suicide attempt in the past year;

• Psychotic disorders;

• Use of narcotic or other sedating medications within 6 hours of testing, which may interfere with cognition;

• Concurrent severe major medical illness (e.g., cancer requiring chemotherapy or resection).

Healthy controls must meet the following inclusion criteria:

• Age > or = 18 years old;

• IQ > or = 70, estimated by the Wechsler Test of Adult Reading (WTAR);

• Capacity to provide informed consent;

• Ability to live independently and complete activities of daily living;

• Fluency in English.

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);

• Other progressive neurologic illness (i.e., malignant brain tumor);

• Moderate or severe traumatic brain injury, or mild trauma within the past 6 months;

• Alcohol or illicit drug abuse within the past year. This information may be obtained by self-report. Subjects will also undergo urine drug testing at the baseline visit. Chronic, stable use of marijuana will not be cause for exclusion. In cases of intermittent, recreational use, it will be required that subjects refrain from marijuana for 2 weeks prior to testing.

• History of a suicide attempt in the past year;

• Psychotic disorders;

• Use of narcotic or other sedating medications within 6 hours of testing, which may interfere with cognition;

• Ongoing major neurological or medical illness (e.g., cancer requiring chemotherapy or resection).