<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/NCT03280342</url>
  </required_header>
  <id_info>
    <org_study_id>FWA00000312-10</org_study_id>
    <nct_id>NCT03280342</nct_id>
  </id_info>
  <brief_title>Cognitive Effects of Immediate Release Topiramate vs Extended Release Topiramate in Patients With Migraine</brief_title>
  <official_title>Cognitive Effects of Immediate Release Topiramate vs Extended Release Topiramate in Patients With Migraine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Supernus Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</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>
      Crossover, randomized, double blind: Q12h dosing in both periods; matching placebo for&#xD;
      evening dosing during XR treatment; target dose: 100mg&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective is to compare the effect of treatment with an immediate-release&#xD;
      topiramate (IR-TPM), namely Topamax®, to an extended-release topiramate (XR-TPM), namely&#xD;
      Trokendi XR®, regimen on cognition in adults with migraine.&#xD;
&#xD;
      The secondary objective is to determine the factors that explain inter-individual variability&#xD;
      in cognitive response. Pharmacokinetic and demographic factors will be explored. Variability&#xD;
      in cognitive response between individuals can be large. A population approach (nonlinear,&#xD;
      mixed effects) will be used to determine drug exposure response relationships.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Sponsor terminated study&#xD;
  </why_stopped>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">September 13, 2018</completion_date>
  <primary_completion_date type="Actual">August 20, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>a crossover, randomized, double blind design in conjunction with intensive pharmacokinetic sampling and multiple administrations of a neurocognitive test battery to directly compare the effects on cognition of IR-TPM to XR-TPM in adults with migraine. The dose will begin at 25mg and titrated in 25mg increments to reach target dose of 100mg.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Controlled Oral Word Association Test (COWA)-generative phonemic fluency</measure>
    <time_frame>Baseline (Day 1) through Day 52</time_frame>
    <description>The primary outcome measure is the Controlled Oral Word Association (COWA: phonemic generative fluency). COWA was chosen as the primary endpoint since in previous studies of drug-induced cognitive impairment, this measure was sensitive to the effects of topiramate (Meador et al, 2003; Marino et al, 2012; Marino et al, 2015). The primary endpoint is a change in the COWA score from baseline to each post-dose assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measures of semantic verbal fluency</measure>
    <time_frame>Baseline (Day 1) through Day 52</time_frame>
    <description>Change in scores from individual baseline to each post-dose assessment on measures of semantic verbal fluency (e.g., Animals)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Digit Span Backward</measure>
    <time_frame>Baseline (Day 1) through Day 52</time_frame>
    <description>Change in scores from individual baseline to each post-dose assessment on measures of working memory (i.e., Digit Span Backward)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Digit Symbol Modalities Test (SDMT)</measure>
    <time_frame>Baseline (Day 1) through Day 52</time_frame>
    <description>Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trails A &amp; B</measure>
    <time_frame>Baseline (Day 1) through Day 52</time_frame>
    <description>Change in scores from individual baseline to each post-dose assessment on measures of executive function</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Migraine</condition>
  <condition>Headache</condition>
  <arm_group>
    <arm_group_label>IR-TPM (Topamax)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IR-TPM (Topamax)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>XR-TPM (Trokendi XR)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IR-TPM (Topamax)</intervention_name>
    <description>XR-TPM (Trokendi XR)</description>
    <arm_group_label>IR-TPM (Topamax)</arm_group_label>
    <arm_group_label>XR-TPM (Trokendi XR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>XR-TPM (Trokendi XR)</intervention_name>
    <description>XR-TPM (Trokendi XR)</description>
    <arm_group_label>IR-TPM (Topamax)</arm_group_label>
    <arm_group_label>XR-TPM (Trokendi XR)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Established history of episodic migraine with or without aura, as assessed by&#xD;
             International Headache Society criteria, for at least 6 months before screening and&#xD;
             frequency of 3 or more headache attacks per month during the past 3 months&#xD;
&#xD;
          2. Male or female, ages 18-65&#xD;
&#xD;
          3. Women are required to be postmenopausal, surgically incapable of bearing children, or&#xD;
             practicing a medically acceptable method of birth control (i.e., double barrier&#xD;
             method, IUD, Mirena, etc) for at least 1 month before study entry through 30 days&#xD;
             following last dose.&#xD;
&#xD;
          4. If postmenopausal and on hormone replacement therapy (HRT) then must to be on a stable&#xD;
             regimen for at least 2 months (continuous stable regimen of cyclic or non-cyclic HRT);&#xD;
             negative pregnancy test.&#xD;
&#xD;
          5. Native English speakers (due to speech and language analysis)&#xD;
&#xD;
          6. Montreal Cognitive Assessment (MoCA) score equal to or greater than 26.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Onset of migraine occurred after age 50 years, or overuse of analgesics or migraine&#xD;
             specific agents for the acute treatment of migraine episodes; examples of analgesic&#xD;
             overuse included the following: more than 8 treatment episodes (episode defined as any&#xD;
             calendar day of usage) of ergot containing medications a month; more than 8 treatment&#xD;
             episodes of triptans a month; or more than 6 treatment episodes of potent opioids a&#xD;
             month.&#xD;
&#xD;
          2. Required, continued use of the following medications for any medical reason during the&#xD;
             study: beta-blockers, benzodiazepines, tricyclic antidepressants, antiepileptics,&#xD;
             calcium channel blockers, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory&#xD;
             drugs (NSAIDs) daily, opioids, agents for insomnia (e.g., Ambien,&#xD;
             diphenhydramine-containing OTC products); corticosteroids, local anesthetics,&#xD;
             botulinum toxin within last three months, or herbal preparations such as feverfew or&#xD;
             St John's wort. However, subjects will be permitted to be on a stable regimen of a&#xD;
             selective serotonin reuptake inhibitor or SNRI for 3 months or more for depression&#xD;
             and/or anxiety.&#xD;
&#xD;
          3. A history of nephrolithiasis&#xD;
&#xD;
          4. Have previously taken topiramate&#xD;
&#xD;
          5. Received an experimental drug or used an experimental or approved device for migraine&#xD;
             prevention (e.g., TENIS unit) within 30 days of screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan Marino, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prism Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>October 30, 2019</last_update_submitted>
  <last_update_submitted_qc>October 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Headache</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Topiramate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03280342
org study id: FWA00000312-10
nct id: NCT03280342
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Crossover, randomized, double blind: Q12h dosing in both periods; matching placebo for
      evening dosing during XR treatment; target dose: 100mg
The primary objective is to compare the effect of treatment with an immediate-release
      topiramate (IR-TPM), namely Topamax®, to an extended-release topiramate (XR-TPM), namely
      Trokendi XR®, regimen on cognition in adults with migraine.

      The secondary objective is to determine the factors that explain inter-individual variability
      in cognitive response. Pharmacokinetic and demographic factors will be explored. Variability
      in cognitive response between individuals can be large. A population approach (nonlinear,
      mixed effects) will be used to determine drug exposure response relationships.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: a crossover, randomized, double blind design in conjunction with intensive pharmacokinetic sampling and multiple administrations of a neurocognitive test battery to directly compare the effects on cognition of IR-TPM to XR-TPM in adults with migraine. The dose will begin at 25mg and titrated in 25mg increments to reach target dose of 100mg.
primary purpose: Treatment
masking: Single (Participant)
measure: Controlled Oral Word Association Test (COWA)-generative phonemic fluency
time frame: Baseline (Day 1) through Day 52
description: The primary outcome measure is the Controlled Oral Word Association (COWA: phonemic generative fluency). COWA was chosen as the primary endpoint since in previous studies of drug-induced cognitive impairment, this measure was sensitive to the effects of topiramate (Meador et al, 2003; Marino et al, 2012; Marino et al, 2015). The primary endpoint is a change in the COWA score from baseline to each post-dose assessment
measure: Measures of semantic verbal fluency
time frame: Baseline (Day 1) through Day 52
description: Change in scores from individual baseline to each post-dose assessment on measures of semantic verbal fluency (e.g., Animals)
measure: Digit Span Backward
time frame: Baseline (Day 1) through Day 52
description: Change in scores from individual baseline to each post-dose assessment on measures of working memory (i.e., Digit Span Backward)
measure: Digit Symbol Modalities Test (SDMT)
time frame: Baseline (Day 1) through Day 52
description: Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed
measure: Trails A & B
time frame: Baseline (Day 1) through Day 52
description: Change in scores from individual baseline to each post-dose assessment on measures of executive function
arm group label: IR-TPM (Topamax)
arm group type: Active Comparator
description: IR-TPM (Topamax)
arm group label: XR-TPM (Trokendi XR)
arm group type: Active Comparator
intervention type: Drug
intervention name: IR-TPM (Topamax)
description: XR-TPM (Trokendi XR)
arm group label: IR-TPM (Topamax)
arm group label: XR-TPM (Trokendi XR)
intervention type: Drug
intervention name: XR-TPM (Trokendi XR)
description: XR-TPM (Trokendi XR)
arm group label: IR-TPM (Topamax)
arm group label: XR-TPM (Trokendi XR)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Susan Marino, PhD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Headache
mesh term: Topiramate
sharing ipd: No