<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04419272</url>
  </required_header>
  <id_info>
    <org_study_id>NURD-003-22S</org_study_id>
    <secondary_id>CX002474</secondary_id>
    <nct_id>NCT04419272</nct_id>
  </id_info>
  <brief_title>Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits</brief_title>
  <official_title>Methylphenidate for the Treatment of Epilepsy-related Cognitive Deficits: a Randomized, Double-blind, Placebo-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>VA New York Harbor Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Portland VA Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Miami VA Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>VA Boston Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Methylphenidate (MPH) is a stimulant, FDA-approved for the treatment of attention deficit&#xD;
      hyperactivity disorder (ADHD). It is unknown, however, if stimulants would be of benefit for&#xD;
      memory and thinking problems due to epilepsy. In this study, participants will be assigned&#xD;
      randomly (i.e., by flip of a coin), to a group that takes MPH and a group that takes a&#xD;
      placebo (sugar pill). Participants will not know the group to which they have been assigned.&#xD;
      Tests of attention and memory will be completed before taking the study pills and at Week 8.&#xD;
      All participants will then have the option of taking MPH for the next two months, and&#xD;
      attention and memory will be tested again at Week 16. The study will determine whether&#xD;
      methylphenidate is helpful for the treatment of attention and memory problems in adults with&#xD;
      epilepsy, and whether the medication is safe and beneficial when taken over an extended time&#xD;
      period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed study is a randomized, double-blind trial of MPH vs. placebo in subjects with&#xD;
      epilepsy and impaired attention. In the blinded phase, subjects will receive placebo or MPH&#xD;
      (titrated to 20mg twice daily) for 8 weeks. Subjects will then receive open-label MPH for 8&#xD;
      weeks (titrated to 20mg twice daily). Cognitive tests will be performed at baseline, Week 8&#xD;
      (the end of the double-blind period), and at Week 16 (the end of the open-label period).&#xD;
&#xD;
      The primary aim is to evaluate the efficacy of MPH for the treatment of attentional&#xD;
      dysfunction in subjects with epilepsy. It is expected that subjects will have improved&#xD;
      attention when taking MPH compared to placebo, measured by the Conner's Continuous&#xD;
      Performance Test (CPT). The effects of MPH on other cognitive functions that rely in part on&#xD;
      attention, including a composite measure of memory (MCG Paragraph Test), psychomotor speed&#xD;
      (Symbol Digit Modalities Test), and divided attention, psychomotor speed, and response&#xD;
      inhibition (Stroop Color Word Interference Test), will be ascertained. Improved performance&#xD;
      when taking MPH compared to placebo is expected. Finally, the study will establish the effect&#xD;
      of MPH on overall quality of life. It is hypothesized that there will be improvement in&#xD;
      self-reported quality of life with MPH, but no change with placebo, as assessed by the&#xD;
      Quality of Life in Epilepsy Patient Inventory.&#xD;
&#xD;
      We will evaluate the safety of MPH compared to placebo with respect to seizure frequency.&#xD;
      Secondary analyses will determine continued efficacy over an open-label period. To control&#xD;
      for practice effects, cognitive performance will be compared to healthy subjects and epilepsy&#xD;
      patients without cognitive complaints, who will complete the repeated cognitive measures but&#xD;
      remain untreated for the duration of the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 14, 2023</start_date>
  <completion_date type="Anticipated">March 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2027</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Parallel group (methylphenidate vs. placebo), followed by open-label methylphenidate</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Conners Continuous Performance Test (CPT), Following Placebo vs. Methylphenidate</measure>
    <time_frame>Week 8</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Composite Measure of Cognition, Following Placebo vs. Methylphenidate</measure>
    <time_frame>Week 8</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Overall Quality of Life, Following Placebo vs. Methylphenidate</measure>
    <time_frame>Week 8</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Composite Measure of Cognition, Post-Open-Label</measure>
    <time_frame>Week 16</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Subjective Cognitive Function, Following Placebo vs. Methylphenidate</measure>
    <time_frame>Week 8</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Subjective Cognitive Function, Post-Open-Label</measure>
    <time_frame>Week 16</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Overall Subjective Quality of Life, Post-Open-Label</measure>
    <time_frame>Week 16</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects on Seizure Frequency</measure>
    <time_frame>Week 8, Week 16</time_frame>
    <description>Seizure occurrence will be recorded in a diary, with frequency compared across baseline, Week 8, and Week 16</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Conner's Continuous Performance Test (CPT), Post-Open-Label</measure>
    <time_frame>Week 16</time_frame>
    <description>Conners Continuous Performance Test (CPT) d' value, a measure of attention, with change compared across baseline, Week 8, and post-open-label (Week 16)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Conners Continuous Performance Test (CPT), Comparing Methylphenidate Group to Untreated Controls</measure>
    <time_frame>Week 8, Week 16</time_frame>
    <description>CPT d' will be compared over the corresponding time periods in the methylphenidate, untreated epilepsy, and healthy control groups</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">226</enrollment>
  <condition>Epilepsy</condition>
  <arm_group>
    <arm_group_label>Methylphenidate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects 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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects 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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open-Label Methylphenidate</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All 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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate</intervention_name>
    <description>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.</description>
    <arm_group_label>Methylphenidate</arm_group_label>
    <other_name>Concerta, Ritalin, Daytrana, Aptensio XR, Metadate CD, Methylin, Quillivant XR, Jornay PM, Adhansia XR, Cotempla</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>sugar pill, lactose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate</intervention_name>
    <description>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.</description>
    <arm_group_label>Open-Label Methylphenidate</arm_group_label>
    <other_name>Concerta, Ritalin, Daytrana, Aptensio XR, Metadate CD, Methylin, Quillivant XR, Jornay PM, Adhansia XR, Cotempla</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. SUBJECTS WITH EPILEPSY&#xD;
&#xD;
             Participants will include adult subjects with focal-onset epilepsy, based on clinical&#xD;
             history, imaging studies and ictal and/or interictal EEG interpreted by a clinical&#xD;
             epileptologist. Seizures may be symptomatic, idiopathic, traumatic, or non- traumatic&#xD;
             in etiology. Subjects must have self-reported cognitive dysfunction. Subjects must&#xD;
             also meet the following eligibility criteria:&#xD;
&#xD;
               -  Age 18 years of age or older;&#xD;
&#xD;
               -  Capacity to provide informed consent;&#xD;
&#xD;
               -  Ability to live independently and complete activities of daily living;&#xD;
&#xD;
               -  Stable seizure frequency at the time of enrollment, such that the subject's&#xD;
                  treating physician does not believe a change in ASM regimen to be warranted&#xD;
                  during the trial (ASMs should remain unchanged during the 16 weeks of&#xD;
                  participation unless absolutely required clinically due an unanticipated change&#xD;
                  in seizure frequency or severity);&#xD;
&#xD;
               -  Fluency in written and spoken English.&#xD;
&#xD;
          2. CONTROLS *DO NOT UNDERGO ANY DRUG OR PLACEBO INTERVENTION Two additional subject&#xD;
             groups will be included, to control for effects of repeated testing in the open-label&#xD;
             extension phase: healthy subjects and epilepsy patients without cognitive complaints,&#xD;
             who will not receive the study drug at any point during the study. Epilepsy patients&#xD;
             without cognitive deficits must otherwise meet all of the above criteria.&#xD;
&#xD;
        Healthy controls must meet the following inclusion criteria:&#xD;
&#xD;
          -  Age 18 years or older;&#xD;
&#xD;
          -  Capacity to provide informed consent;&#xD;
&#xD;
          -  Ability to live independently and complete activities of daily living;&#xD;
&#xD;
          -  Fluency in written and spoken English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        SUBJECTS WITH EPILEPSY&#xD;
&#xD;
        Subjects with epilepsy with or without cognitive complaints will be excluded from&#xD;
        participation for:&#xD;
&#xD;
          -  Psychogenic, non-epileptic spells&#xD;
&#xD;
          -  Delirium in the past year&#xD;
&#xD;
          -  Other progressive neurologic illness (i.e., malignant brain tumor). A benign, stable&#xD;
             neoplasm with no plans for resection will not be cause for exclusion.&#xD;
&#xD;
          -  A history of alcohol or illicit drug abuse;&#xD;
&#xD;
          -  Generalized tonic-clonic or other generalized motor seizure(s) within 48 hours or&#xD;
             focal-onset seizures with impaired awareness within 24 hours of neuropsychological&#xD;
             testing;&#xD;
&#xD;
          -  Status epilepticus in the past year;&#xD;
&#xD;
          -  Neurosurgery within the past 6 months;&#xD;
&#xD;
          -  Suicide attempt in the past year and/or high-risk suicide flag in the medical record;&#xD;
&#xD;
          -  Psychotic disorders&#xD;
&#xD;
          -  Severe anxiety (&gt;26 on the Beck Anxiety Inventory [BAI]) and impulse control&#xD;
             disorders;&#xD;
&#xD;
          -  Untreated sleep disorders;&#xD;
&#xD;
          -  Use of narcotic or other sedating medications within 6 hours of testing (i.e.,&#xD;
             diphenhydramine);&#xD;
&#xD;
          -  Concurrent severe major medical illness (i.e., cancer requiring chemotherapy or&#xD;
             resection)&#xD;
&#xD;
          -  Prior transient ischemic attack (TIA) or stroke&#xD;
&#xD;
        Subjects with epilepsy will also be excluded for a diagnosis of dementia (i.e., Alzheimer's&#xD;
        disease). Subjects with epilepsy and cognitive complaints must have a MoCA score 22.&#xD;
        Subjects with epilepsy and no cognitive complaints must have a MoCA score 26.&#xD;
&#xD;
        Subjects with epilepsy and cognitive complaints must meet additional exclusion criteria, to&#xD;
        minimize risks of MPH:&#xD;
&#xD;
          -  Current pregnancy or pregnancy planned during the trial&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or MAOI use within 14&#xD;
             days of beginning the trial;&#xD;
&#xD;
          -  Structural cardiac abnormalities, cardiomyopathy, serious arrhythmias, or coronary&#xD;
             artery disease (including a history of myocardial infarction, cardiac stent placement,&#xD;
             coronary artery bypass graft surgery, or angina);&#xD;
&#xD;
          -  Bipolar disorders;&#xD;
&#xD;
          -  Concurrent use of medications for erectile dysfunction (e.g., tadalafil, sildenafil);&#xD;
&#xD;
          -  Use of medications that may lower seizure threshold (e.g., tramadol, bupropion) or&#xD;
             induce psychosis (i.e., varenicline);&#xD;
&#xD;
          -  Known MPH allergy;&#xD;
&#xD;
          -  Uncontrolled hypertension;&#xD;
&#xD;
        HEALTHY CONTROLS&#xD;
&#xD;
        Healthy controls will be excluded based on the following criteria:&#xD;
&#xD;
          -  History of seizures, epilepsy, or psychogenic, non-epileptic spells;&#xD;
&#xD;
          -  Diagnosis of dementia (i.e., Alzheimer's disease), MoCA score of &lt;26;&#xD;
&#xD;
          -  Delirium in the past year;&#xD;
&#xD;
          -  Other progressive neurologic illness (i.e., malignant brain tumor);&#xD;
&#xD;
          -  Prior moderate or severe traumatic brain injury (TBI);&#xD;
&#xD;
          -  Mild TBI within the past 6 months;&#xD;
&#xD;
          -  A history of alcohol or illicit drug abuse;&#xD;
&#xD;
          -  Suicide attempt in the past year and/or high-risk suicide flag in the medical record;&#xD;
&#xD;
          -  Psychotic, severe anxiety (BAI &gt;26), or impulse control disorders;&#xD;
&#xD;
          -  Untreated sleep disorders;&#xD;
&#xD;
          -  Use of narcotic or other sedating medications within 6 hours of testing;&#xD;
&#xD;
          -  Ongoing major neurological or medical illness (i.e., cancer requiring chemotherapy or&#xD;
             resection);&#xD;
&#xD;
          -  Prior TIA or stroke;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Beth A Leeman-Markowski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Beth A Leeman-Markowski, MD</last_name>
    <phone>(212) 686-7500</phone>
    <phone_ext>5133</phone_ext>
    <email>beth.leeman-markowski@va.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Samantha P Martin, MA</last_name>
    <phone>(212) 685-7500</phone>
    <email>Samantha.Martin1@va.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Miami VA Healthcare System, Miami, FL</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marcella Coutts, MD</last_name>
      <phone>305-575-7000</phone>
      <phone_ext>14144</phone_ext>
      <email>marcella.coutts@va.gov</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02130-4817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David C McCarthy, MD</last_name>
      <phone>857-364-4750</phone>
      <email>david.mccarthy@va.gov</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10010-5011</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beth A Leeman-Markowski, MD</last_name>
      <phone>212-686-7500</phone>
      <phone_ext>5133</phone_ext>
      <email>beth.leeman-markowski@va.gov</email>
    </contact>
    <contact_backup>
      <last_name>Samantha P Martin, MA</last_name>
      <phone>(212) 685-7500</phone>
      <email>Samantha.Martin1@va.gov</email>
    </contact_backup>
    <investigator>
      <last_name>Beth A Leeman-Markowski, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>VA Portland Health Care System, Portland, OR</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97207-2964</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marissa Kellogg, MD</last_name>
      <phone>503-418-9712</phone>
      <email>kellogma@ohsu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>attention</keyword>
  <keyword>memory</keyword>
  <keyword>cognition</keyword>
  <keyword>seizure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
    <mesh_term>Cognition Disorders</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_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.</ipd_time_frame>
    <ipd_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.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04419272
org study id: NURD-003-22S
secondary id: CX002474
nct id: NCT04419272
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel group (methylphenidate vs. placebo), followed by open-label methylphenidate
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: 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.
measure: Change in Conners Continuous Performance Test (CPT), Following Placebo vs. Methylphenidate
time frame: Week 8
description: 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
measure: Change in Composite Measure of Cognition, Following Placebo vs. Methylphenidate
time frame: Week 8
description: 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.
measure: Change in Overall Quality of Life, Following Placebo vs. Methylphenidate
time frame: Week 8
description: 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.
measure: Change in Composite Measure of Cognition, Post-Open-Label
time frame: Week 16
description: 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)
measure: Change in Subjective Cognitive Function, Following Placebo vs. Methylphenidate
time frame: Week 8
description: 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.
measure: Change in Subjective Cognitive Function, Post-Open-Label
time frame: Week 16
description: 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)
measure: Change in Overall Subjective Quality of Life, Post-Open-Label
time frame: Week 16
description: 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.
measure: Effects on Seizure Frequency
time frame: Week 8, Week 16
description: Seizure occurrence will be recorded in a diary, with frequency compared across baseline, Week 8, and Week 16
measure: Change in Conner's Continuous Performance Test (CPT), Post-Open-Label
time frame: Week 16
description: Conners Continuous Performance Test (CPT) d' value, a measure of attention, with change compared across baseline, Week 8, and post-open-label (Week 16)
measure: Change in Conners Continuous Performance Test (CPT), Comparing Methylphenidate Group to Untreated Controls
time frame: Week 8, Week 16
description: CPT d' will be compared over the corresponding time periods in the methylphenidate, untreated epilepsy, and healthy control groups
arm group label: Methylphenidate
arm group type: Experimental
description: Subjects 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects 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.
arm group label: Open-Label Methylphenidate
arm group type: Other
description: All 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.
intervention type: Drug
intervention name: Methylphenidate
description: 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.
arm group label: Methylphenidate
other name: Concerta, Ritalin, Daytrana, Aptensio XR, Metadate CD, Methylin, Quillivant XR, Jornay PM, Adhansia XR, Cotempla
intervention type: Other
intervention name: Placebo
description: 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.
arm group label: Placebo
other name: sugar pill, lactose
intervention type: Drug
intervention name: Methylphenidate
description: 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.
arm group label: Open-Label Methylphenidate
other name: Concerta, Ritalin, Daytrana, Aptensio XR, Metadate CD, Methylin, Quillivant XR, Jornay PM, Adhansia XR, Cotempla
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Beth A Leeman-Markowski, MD
role: Principal Investigator
affiliation: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
last name: Beth A Leeman-Markowski, MD
phone: (212) 686-7500
phone ext: 5133
email: beth.leeman-markowski@va.gov
last name: Samantha P Martin, MA
phone: (212) 685-7500
email: Samantha.Martin1@va.gov
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Cognition Disorders
mesh term: Cognitive Dysfunction
mesh term: Methylphenidate
sharing ipd: Yes
ipd description: 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.
ipd info type: Study Protocol
ipd 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.
ipd 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.