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.
The proposed study is a randomized, double-blind trial of MPH vs. placebo in subjects with epilepsy and impaired attention. In the blinded phase, subjects will receive placebo or MPH (titrated to 20mg twice daily) for 8 weeks. Subjects will then receive open-label MPH for 8 weeks (titrated to 20mg twice daily). Cognitive tests will be performed at baseline, Week 8 (the end of the double-blind period), and at Week 16 (the end of the open-label period). The primary aim is to evaluate the efficacy of MPH for the treatment of attentional dysfunction in subjects with epilepsy. It is expected that subjects will have improved attention when taking MPH compared to placebo, measured by the Conner's Continuous Performance Test (CPT). The effects of MPH on other cognitive functions that rely in part on attention, including a composite measure of memory (MCG Paragraph Test), psychomotor speed (Symbol Digit Modalities Test), and divided attention, psychomotor speed, and response inhibition (Stroop Color Word Interference Test), will be ascertained. Improved performance when taking MPH compared to placebo is expected. Finally, the study will establish the effect of MPH on overall quality of life. It is hypothesized that there will be improvement in self-reported quality of life with MPH, but no change with placebo, as assessed by the Quality of Life in Epilepsy Patient Inventory. We will evaluate the safety of MPH compared to placebo with respect to seizure frequency. Secondary analyses will determine continued efficacy over an open-label period. To control for practice effects, cognitive performance will be compared to healthy subjects and epilepsy patients without cognitive complaints, who will complete the repeated cognitive measures but remain untreated for the duration of the trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
226
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.
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.
Miami VA Healthcare System, Miami, FL
Miami, Florida, United States
RECRUITINGVA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, United States
RECRUITINGVA NY Harbor Healthcare System, New York, NY
New York, New York, United States
RECRUITINGVA Portland Health Care System, Portland, OR
Portland, Oregon, United States
RECRUITINGChange 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
Time frame: Week 8
Change in Composite Measure of Cognition, Following Placebo vs. Methylphenidate
Scores on the MCG Paragraph (immediate and delayed recall), Symbol Digit Modality Test (SDMT), and Stroop tasks will be integrated into an omnibus outcome variable by combining performance based upon z-scores derived from normative tables. The omnibus score will be compared following placebo vs. active drug treatment.
Time frame: Week 8
Change in Overall Quality of Life, Following Placebo vs. Methylphenidate
Self-reported quality of life, as assessed by the Quality of Life in Epilepsy Inventory (QOLIE-89), compared post-placebo vs. post-methylphenidate. Range of scores 0-100, with higher scores representing better quality of life.
Time frame: Week 8
Change in Composite Measure of Cognition, Post-Open-Label
Scores on the MCG Paragraph (immediate and delayed recall), Symbol Digit Modality Test (SDMT), and Stroop tasks will be integrated into an omnibus outcome variable by combining performance based upon z-scores derived from normative tables. The omnibus score will be compared across baseline, Week 8, and post-open-label (Week 16)
Time frame: Week 16
Change in Subjective Cognitive Function, Following Placebo vs. Methylphenidate
Self-reported cognitive function, as assessed by the attention/concentration subscale of the Quality of Life in Epilepsy Inventory (QOLIE-89), compared post-placebo vs. post-methylphenidate.
Time frame: Week 8
Change in Subjective Cognitive Function, Post-Open-Label
Self-reported cognitive function, as assessed by the attention/concentration subscale of the Quality of Life in Epilepsy Inventory (QOLIE-89), compared across baseline, Week 8, and post-open-label (Week 16)
Time frame: Week 16
Change in Overall Subjective Quality of Life, Post-Open-Label
Self-reported quality of life, as assessed by the Quality of Life in Epilepsy Inventory (QOLIE-89), compared across baseline, Week 8, and post-open-label. Range of scores 0-100, with higher scores representing better quality of life.
Time frame: Week 16
Effects on Seizure Frequency
Seizure occurrence will be recorded in a diary, with frequency compared across baseline, Week 8, and Week 16
Time frame: Week 8, Week 16
Change in Conner's Continuous Performance Test (CPT), Post-Open-Label
Conners Continuous Performance Test (CPT) d' value, a measure of attention, with change compared across baseline, Week 8, and post-open-label (Week 16)
Time frame: Week 16
Change in Conners Continuous Performance Test (CPT), Comparing Methylphenidate Group to Untreated Controls
CPT d' will be compared over the corresponding time periods in the methylphenidate, untreated epilepsy, and healthy control groups
Time frame: Week 8, Week 16
Change in Digit Span Following Placebo vs. Methylphenidate
Total Digit Span score, compared post-placebo vs. post-methylphenidate. Range of scores 0-48, with higher scores indicating better performance.
Time frame: Week 8
Change in Digit Span, Post-Open-Label
Total Digit Span score, with change compared across baseline, Week 8, and post-open-label (Week 16)
Time frame: Week 16
Visual Paired Comparison Task Novelty Preference Score Following Placebo vs. Methylphenidate
Novelty preference score (range 0-100%), compared post-placebo vs. post-methylphenidate. Higher scores indicate better performance. (Manhattan site only)
Time frame: Week 8
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