Methylphenidate Treatment of Attention Deficits in Epilepsy
Condition: Epilepsy; Cognitive Deficits; Attention Deficits
MeSH terms: Epilepsy; Attention Deficit Disorder with Hyperactivity; Cognition Disorders; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 4

Summary: 
      Methylphenidate (MPH) has long been used to improve attention and cognitive difficulties
      associated with ADHD, including in children with ADHD and epilepsy (Torres et al., 2008).
      Methylphenidate (MPH) is also helpful in treating attention and other cognitive difficulties
      in a variety of other neurological and medical conditions (Kajs-Wyllie, 2002; Prommer, 2012).
      We seek to evaluate the potential efficacy and safety of this medication in treating
      attention deficits, as well as other cognitive difficulties, experienced by adult patients
      with epilepsy.

      To our knowledge, there are currently very few studies which explicitly examine the impact of
      MPH on measureable attention deficits and other cognitive deficits in adult patients with
      epilepsy. We hope to quantify what impact, if any, methylphenidate has on attention, in
      addition to other specific measureable cognitive functions, in patients with cognitive
      complaints and epilepsy, and contribute to a growing body of evidence which supports the
      safety of methylphenidate's use for attention deficits in patients with epilepsy. As other
      effective treatments for attention and other cognitive difficulties in patients with epilepsy
      are not currently available, MPH could represent an important option in the treatment of such
      patients.
    

Detailed description: 
      Prospective participants with seizures will be identified primarily through the Stanford
      Neurology and Neuropsychiatry clinics and Stanford Medical Center, with the assistance of
      clinic staff and providers. Participants may also be identified and referred by their
      physicians in the community as well. Informational fliers will be distributed to these
      clinics and throughout Stanford Medical Center and Stanford campus in order to identify
      participants with epilepsy as well as healthy volunteers. Prospective participants may also
      contact study staff directly via contact information listed on the flier or provided to them
      by their providers. Those identified will be contacted, either in person or by telephone, by
      study staff.

      A telephone or in-person pre-screening will occur, expected to last approximately 20-30
      minutes, in order to determine eligibility for the study, interest in participating, and any
      questions related to the study. A brief summary of study procedures and goals will be
      reviewed during this pre-screening. Participants who meet inclusion/exclusion criteria may
      take part in an initial in-person visit at Stanford Medical Center, where informed consent
      will be obtained and signed (see attached informed consent form). Any additional history
      needed in order to confirm a participant's eligibility will be reviewed at this visit. If the
      individual chooses to proceed, the participant's blood pressure and heartrate will be
      measured, and if necessary (because a recent physical exam including cardiac auscultation is
      not available), a brief physical exam will be performed by a licensed physician. If vital
      signs and exam (if necessary) are normal, participants will be asked to complete
      neuropsychiatric questionnaires, self-report questionnaires, a quality-of-life questionnaire,
      and a seizure diary. The full 40-minute neurocognitive battery will be performed, and
      baseline scores obtained.

      Participants will be asked to complete the seizure diary once per week, either in-person at
      their visits or at home. Thereafter, the participant will be asked to attend at least three
      additional 2-hour sessions at Stanford Medical Center. The participant will be asked to avoid
      taking any non-routine sedating medications within 24 hours of his/her scheduled visit, and
      to refrain from eating, drinking caffeine, or smoking for 2 hours prior to his/her visit.
      When the participant arrives, they will be given either a placebo, 20mg of methylphenidate,
      or 10mg of methylphenidate (randomized and blinded by the research pharmacy), and asked to
      remain within the hospital for 1 hour prior to testing to allow the medication to enter their
      system. Both study staff and the participant will be blinded to whether they are receiving
      active medication or placebo. During this time, the participant will complete self-report
      questionnaires reporting any medication changes, medical events, or significant adverse
      events, and their seizure diary will be reviewed and kept by study staff. After this, the
      full neurocognitive battery will be completed. Following the completion of neurocognitive
      testing, the participant's next visit will be scheduled for approximately the same time of
      day in approximately one week, and payment will be provided. This procedure will be repeated
      for the next two visits. Participants will not receive any additional study drug during this
      period other than the single dose they receive in-person.

      At the participant's fourth visit, they will be asked to repeat the neuropsychiatric
      questionnaires from visit #1, as well as the usual self-report forms and seizure diary.
      Heartrate and blood pressure will be obtained again prior to the administration of the
      neurocognitive battery. At the end of the fourth visit, participants will be asked if they
      wish to take part in the four-week open-label phase of this study, designed to evaluate the
      ongoing efficacy and safety of methylphenidate for use in patients with epilepsy. Regardless
      of their answer, payment will be provided for their fourth visit.

      Those participants who are interested in participating in the open-label trial will be
      provided with a prescription for two weeks of methylphenidate 10mg PO BID, followed by two
      weeks of methylphenidate 20mg PO BID. Participants will be provided with copies of the
      seizure diary and asked to complete it weekly. Participants will be able to contact the
      protocol director by phone to report any significant side effects or adverse events during
      this trial. At the protocol director's discretion, in keeping with standard of care for this
      medication, the dosage of the medication may be lowered (minimum dose 5mg PO BID) in response
      to any side effects experienced by participants during this period.

      Participants in the open-label trial will be asked to return after four more weeks for a
      fifth and final visit. Participants will again be asked to refrain from eating, caffeine, and
      nicotine for 2 hours prior to their visit, and will take their prescribed methylphenidate
      upon arriving at Stanford Medical Center. Participants will wait 1 hour for the medication to
      enter their system, during which time they will complete neuropsychiatric and self-report
      questionnaires as before, their seizure diaries will be reviewed, and their heart rate and
      blood pressure will again be measured. The cognitive battery will be administered again.
      Afterwards, any participant questions will be answered and final financial compensation will
      be provided, and the participant's involvement has ended. Data will remain blinded until the
      completion of the study. Participants wishing to receive the active medication following the
      termination of the open-label phase of the study may do so at the discretion of their
      physicians.
    

Intervention name(s): Methylphenidate
Intervention type(s): Drug
Intervention description(s): Participants with epilepsy will first receive blinded, single-dose capsules which contain either:
Placebo 20mg of methylphenidate or 10mg of methylphenidate.
At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.
Other intervention name(s): Ritalin
Intervention MeSH terms: Methylphenidate
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment