Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits
2 other identifiers
interventional
226
1 country
4
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Aug 2023
Longer than P75 for phase_4
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 28, 2020
CompletedFirst Posted
Study publicly available on registry
June 5, 2020
CompletedStudy Start
First participant enrolled
August 14, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2028
April 20, 2026
April 1, 2026
4.8 years
May 28, 2020
April 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Conners Continuous Performance Test (CPT), Following Placebo vs. Methylphenidate
Conners Continuous Performance Test (CPT) d' value, a measure of attention, compared post-placebo vs. post-methylphenidate (MPH) in a double-blind, parallel group, placebo controlled, randomized design
Week 8
Secondary Outcomes (12)
Change in Composite Measure of Cognition, Following Placebo vs. Methylphenidate
Week 8
Change in Overall Quality of Life, Following Placebo vs. Methylphenidate
Week 8
Change in Composite Measure of Cognition, Post-Open-Label
Week 16
Change in Subjective Cognitive Function, Following Placebo vs. Methylphenidate
Week 8
Change in Subjective Cognitive Function, Post-Open-Label
Week 16
- +7 more secondary outcomes
Study Arms (3)
Methylphenidate
EXPERIMENTALSubjects 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.
Placebo
PLACEBO COMPARATORSubjects 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.
Open-Label Methylphenidate
OTHERAll 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.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- 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.
You may not qualify if:
- 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
- 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
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- VA Office of Research and Developmentlead
- VA New York Harbor Healthcare Systemcollaborator
- Portland VA Medical Centercollaborator
- Miami VA Healthcare Systemcollaborator
- VA Boston Healthcare Systemcollaborator
Study Sites (4)
Miami VA Healthcare System, Miami, FL
Miami, Florida, 33125, United States
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130-4817, United States
VA NY Harbor Healthcare System, New York, NY
New York, New York, 10010-5011, United States
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97207-2964, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Beth A Leeman-Markowski, MD
VA NY Harbor Healthcare System, New York, NY
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double-blind, placebo-controlled study. A designated unblinded study team member will perform the randomization and provide group assignment to the local Research Pharmacies. The unblinded study team member and Research Pharmacies will hold the randomization key, while all other individuals are blinded to study group assignment.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 28, 2020
First Posted
June 5, 2020
Study Start
August 14, 2023
Primary Completion (Estimated)
May 31, 2028
Study Completion (Estimated)
May 31, 2028
Last Updated
April 20, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Data will be made available no later than one year following publication. Data will be available for at least 6 years following completion of the study.
- Access Criteria
- The data will be shared pending a written agreement 1) prohibiting the recipient from identification or re-identification of the data and forbidding any attempts to do so, and 2) allowing scientific use only.
An anonymized data set may be shared upon written request to the PI and available no later than one year following publication. The data will be shared pending a written agreement 1) prohibiting the recipient from identification or re-identification of the data and forbidding any attempts to do so, and 2) allowing scientific use only. The data set will be provided via encrypted VA email.