<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/NCT03773562</url>
  </required_header>
  <id_info>
    <org_study_id>18-001497</org_study_id>
    <nct_id>NCT03773562</nct_id>
  </id_info>
  <brief_title>Imaging the Migraine Brain Pre- and Post-Erenumab</brief_title>
  <official_title>Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aims of this study are to:&#xD;
&#xD;
        1. Identify changes in brain function and structure that correlate with response to&#xD;
           erenumab.&#xD;
&#xD;
        2. Develop models using imaging data +/- clinical data to predict which patients will&#xD;
           respond to erenumab. Pre-treatment and early post-treatment imaging data will be used&#xD;
           separately for predictive modeling.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will include 50 participants with migraine aged 18-65 years who have 10-25 migraine&#xD;
      days per month at baseline. Following a 4-week headache diary run-in phase, participants will&#xD;
      receive two treatments with once monthly subcutaneous injections of erenumab 140 mg.&#xD;
      Questionnaires, structured interviews, cognitive tests, quantitative sensory testing and&#xD;
      brain imaging will be performed prior to and following erenumab treatment. These data will be&#xD;
      collected at early time points after the first treatment as well as at eight weeks following&#xD;
      the first treatment to allow for identification of early and late effects of erenumab on&#xD;
      clinical, physiologic, and imaging outcomes and to determine if early physiologic and imaging&#xD;
      outcomes predict clinical outcomes at eight weeks. Physiologic and imaging data will be&#xD;
      compared to already collected data from healthy controls so as to interpret changes that are&#xD;
      seen following treatment with erenumab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 25, 2019</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>All consented and qualifying subjects will receive erenumab treatment. Questionnaires, cognitive testing, and brain MRIs will be completed pre- and post-treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Pain-Induced Brain Activations</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Changes in pain-induced regional brain activations (BOLD response) from baseline (pre-treatment) to 8 weeks post-treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Brain Functional Connectivity (temporal correlations in BOLD signal fluctuations)</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Changes in brain functional connectivity (temporal correlations in BOLD signal fluctuations) amongst a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Accuracy of Predicting Treatment Response</measure>
    <time_frame>Baseline, 2 weeks, 5-8 weeks</time_frame>
    <description>Multivariate machine-learning modeling of brain structural and functional data +/- clinical data collected at baseline and at 2 weeks will be utilized for predicting treatment responses measured between 5 and 8 weeks post-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early Changes in Pain-Induced Brain Activations</measure>
    <time_frame>Baseline, 2 weeks</time_frame>
    <description>Changes in pain-induced regional brain activations (BOLD response) from baseline (pre-treatment) to 2 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early Changes in Brain Functional Connectivity (temporal correlations in BOLD signal fluctuations)</measure>
    <time_frame>Baseline, 2 weeks</time_frame>
    <description>Changes in brain functional connectivity (temporal correlations in BOLD signal fluctuations) amongst a priori selected regions of interest from baseline (pre-treatment) to 2 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Brain Perfusion</measure>
    <time_frame>Baseline, 2 weeks, 8 weeks</time_frame>
    <description>Changes in arterial spin labeling measures of cerebral blood flow from baseline (pre-treatment) to 2 weeks and 8 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Brain Regional Volumes</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Changes in regional volumes of a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Brain Cortical Thickness</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Changes in the cortical thickness of a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Brain White Matter Tract Integrity</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Changes in the integrity of a priori selected white matter tracts measured via diffusion tensor imaging</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>Erenumab</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erenumab</intervention_name>
    <description>Erenumab will be used per label instructions.</description>
    <arm_group_label>Erenumab</arm_group_label>
    <other_name>Aimovig</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  18-65 years of age&#xD;
&#xD;
          -  Episodic migraine (with or without aura) or chronic migraine according to the&#xD;
             diagnostic criteria included within the International Classification of Headache&#xD;
             Disorders 3 (ICHD-3)&#xD;
&#xD;
          -  6-25 migraine days per month on average over the 3 months prior to screening,&#xD;
             confirmed by run-in phase prospective data collection&#xD;
&#xD;
          -  Duration since migraine onset of at least 12 months prior to screening based on&#xD;
             medical records and/or patient self-report&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Older than 50 years of age at migraine onset&#xD;
&#xD;
          -  History of cluster headache or hemiplegic migraine&#xD;
&#xD;
          -  Continuous headache pain (i.e. no pain-free periods of any duration during the one&#xD;
             month before screening)&#xD;
&#xD;
          -  Opioid- or butalbital-containing analgesics on 6 or more days per month during the 2&#xD;
             months prior to the start of the baseline phase&#xD;
&#xD;
          -  History of major psychiatric disorder such as schizophrenia and bipolar disorder&#xD;
&#xD;
          -  History or evidence of any unstable or clinically significant medical condition, that&#xD;
             in the opinion of the investigator, would pose a risk to subject safety or interfere&#xD;
             with the study evaluation, procedures, or completion&#xD;
&#xD;
          -  No therapeutic response in migraine prevention after an adequate therapeutic trial of&#xD;
             4 or more of the following medication categories: Category 1- divalproex sodium,&#xD;
             sodium valproate; Category 2- topiramate; Category 3- beta-blockers; Category 4-&#xD;
             tricyclic antidepressants; Category 5- venlafaxine or desvenlafaxine, duloxetine or&#xD;
             milnacipran; Category 6- flunarizine, verapamil; Category 7- lisinopril, candesartan;&#xD;
             Category 8- botulinum toxin. No therapeutic response is defined as no reduction in&#xD;
             headache frequency, duration, or severity after administration of the medication for&#xD;
             at least 6 weeks at the generally accepted therapeutic dose(s) based on the&#xD;
             investigator's assessment. Lack of sustained response to a medication and failure to&#xD;
             tolerate a therapeutic dose are not considered to be &quot;no therapeutic response&quot;.&#xD;
&#xD;
          -  Concomitant use of 3 or more of the following medications for migraine prevention&#xD;
             within 2 months before the start of the baseline phase or throughout the study:&#xD;
             divalproex sodium, sodium valproate, topiramate, carbamazepine, gabapentin,&#xD;
             beta-blockers, tricyclic antidepressants, venlafaxine, desvenlafaxine, duloxetine,&#xD;
             milnacipran, flunarizine, verapamil, lomerizine, lisinopril, candesartan, clonidine,&#xD;
             guanfacine, cyproheptadine, methysergide, pizotifen, butterbur, feverfew, magnesium&#xD;
             (at least 600 mg per day), riboflavin (at least 100 mg per day). Use of up to two&#xD;
             medications is permitted as long as the dose has been stable for at least 2 months&#xD;
             before the start of the run-in phase and during the study.&#xD;
&#xD;
          -  Botulinum toxin (in the head and/or neck region) within 4 months before the start of&#xD;
             the baseline phase and throughout the study&#xD;
&#xD;
          -  Ergotamine derivatives, steroids, and triptans used for migraine prophylaxis within 2&#xD;
             months before the start of the baseline phase and throughout the study&#xD;
&#xD;
          -  Procedures (e.g. nerve blocks) used for migraine prophylaxis within 2 months before&#xD;
             the start of the baseline phase and throughout the study&#xD;
&#xD;
          -  History of myocardial infarction, stroke, transient ischemic attack, unstable angina,&#xD;
             coronary artery bypass surgery, or other revascularization procedures within 12 months&#xD;
             prior to screening.&#xD;
&#xD;
          -  Contraindications to MRI including, but not limited to: Metal implants, aneurysm&#xD;
             clips, severe claustrophobia, implanted electronic devices, insulin or infusion pump,&#xD;
             cochlear/otologic/ear implant, non-removable prosthesis, implanted shunts/catheters,&#xD;
             certain intrauterine devices, tattooed makeup, body piercings that cannot be removed,&#xD;
             metal fragments, wire sutures or metal staples.&#xD;
&#xD;
          -  Factors that Reduce MR Image Quality and Interpretability: dental braces or other&#xD;
             non-removable devices (e.g. retainers); prior brain surgery; known brain MRI&#xD;
             abnormality that in the investigator's opinion will significantly impact MRI data&#xD;
&#xD;
          -  Sensory disorders that in the investigator's opinion might affect perception of&#xD;
             cutaneous thermal stimuli (e.g. peripheral neuropathy)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  Not willing to use a reliable form of contraception (for women of childbearing&#xD;
             potential) through 16 weeks after the last dose of erenumab. Acceptable methods of&#xD;
             birth control include not having intercourse, hormonal birth control methods,&#xD;
             intrauterine devices, surgical contraceptive methods, or two barrier methods (each&#xD;
             partner must use a barrier method) with spermicide. A reliable form of contraception&#xD;
             must be started prior to or at the time of starting the run-in phase. Not being of&#xD;
             childbearing potential is defined as any woman who: 1) is post-menopausal by history,&#xD;
             defined as: a) At least 55 years of age with cessation of menses for 12 or more&#xD;
             months, OR b) Younger than 55 years of age but no spontaneous menses for at least 2&#xD;
             years, OR c)Younger than 55 years of age and spontaneous menses within the past 1&#xD;
             year, but currently amenorrheic (e.g. spontaneous or secondary to hysterectomy), AND&#xD;
             with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating&#xD;
             hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL)&#xD;
             or according to the definition of &quot;postmenopausal range&quot; for the laboratory involved,&#xD;
             OR d) Underwent bilateral oophorectomy, OR e) Underwent hysterectomy, OR f) Underwent&#xD;
             bilateral salpingectomy&#xD;
&#xD;
          -  Currently receiving treatment in another drug study or an investigational device&#xD;
             study, or less than 90 days prior to screening since ending treatment on another&#xD;
             investigational device or drug study(-ies)&#xD;
&#xD;
          -  Has received CGRP monoclonal antibody within 4 months of the start of the run-in phase&#xD;
&#xD;
          -  Active chronic pain condition that in the investigator's opinion is unrelated to&#xD;
             migraine (e.g. chronic pelvic pain)&#xD;
&#xD;
          -  Acute pain condition that in the investigator's opinion is unrelated to migraine (e.g.&#xD;
             post-surgical pain)&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Less than 80% compliance with providing headache diary data during the run-in phase&#xD;
             (i.e. provides data on less than 80% of days)&#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>Todd J Schwedt</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>August 8, 2022</last_update_submitted>
  <last_update_submitted_qc>August 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Todd J. Schwedt</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Brain Structure</keyword>
  <keyword>Brain Function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erenumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 26, 2023</submitted>
    <returned>July 21, 2023</returned>
  </pending_results>
  <!-- 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/NCT03773562
org study id: 18-001497
nct id: NCT03773562
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The aims of this study are to:

        1. Identify changes in brain function and structure that correlate with response to
           erenumab.

        2. Develop models using imaging data +/- clinical data to predict which patients will
           respond to erenumab. Pre-treatment and early post-treatment imaging data will be used
           separately for predictive modeling.
The study will include 50 participants with migraine aged 18-65 years who have 10-25 migraine
      days per month at baseline. Following a 4-week headache diary run-in phase, participants will
      receive two treatments with once monthly subcutaneous injections of erenumab 140 mg.
      Questionnaires, structured interviews, cognitive tests, quantitative sensory testing and
      brain imaging will be performed prior to and following erenumab treatment. These data will be
      collected at early time points after the first treatment as well as at eight weeks following
      the first treatment to allow for identification of early and late effects of erenumab on
      clinical, physiologic, and imaging outcomes and to determine if early physiologic and imaging
      outcomes predict clinical outcomes at eight weeks. Physiologic and imaging data will be
      compared to already collected data from healthy controls so as to interpret changes that are
      seen following treatment with erenumab.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: All consented and qualifying subjects will receive erenumab treatment. Questionnaires, cognitive testing, and brain MRIs will be completed pre- and post-treatment.
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in Pain-Induced Brain Activations
time frame: Baseline, 8 weeks
description: Changes in pain-induced regional brain activations (BOLD response) from baseline (pre-treatment) to 8 weeks post-treatment
measure: Changes in Brain Functional Connectivity (temporal correlations in BOLD signal fluctuations)
time frame: Baseline, 8 weeks
description: Changes in brain functional connectivity (temporal correlations in BOLD signal fluctuations) amongst a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment
measure: Accuracy of Predicting Treatment Response
time frame: Baseline, 2 weeks, 5-8 weeks
description: Multivariate machine-learning modeling of brain structural and functional data +/- clinical data collected at baseline and at 2 weeks will be utilized for predicting treatment responses measured between 5 and 8 weeks post-treatment.
measure: Early Changes in Pain-Induced Brain Activations
time frame: Baseline, 2 weeks
description: Changes in pain-induced regional brain activations (BOLD response) from baseline (pre-treatment) to 2 weeks post-treatment
measure: Early Changes in Brain Functional Connectivity (temporal correlations in BOLD signal fluctuations)
time frame: Baseline, 2 weeks
description: Changes in brain functional connectivity (temporal correlations in BOLD signal fluctuations) amongst a priori selected regions of interest from baseline (pre-treatment) to 2 weeks post-treatment
measure: Changes in Brain Perfusion
time frame: Baseline, 2 weeks, 8 weeks
description: Changes in arterial spin labeling measures of cerebral blood flow from baseline (pre-treatment) to 2 weeks and 8 weeks post-treatment
measure: Changes in Brain Regional Volumes
time frame: Baseline, 8 weeks
description: Changes in regional volumes of a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment
measure: Changes in Brain Cortical Thickness
time frame: Baseline, 8 weeks
description: Changes in the cortical thickness of a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment
measure: Changes in Brain White Matter Tract Integrity
time frame: Baseline, 8 weeks
description: Changes in the integrity of a priori selected white matter tracts measured via diffusion tensor imaging
arm group label: Erenumab
arm group type: Other
description: All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later.
intervention type: Drug
intervention name: Erenumab
description: Erenumab will be used per label instructions.
arm group label: Erenumab
other name: Aimovig
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Todd J Schwedt
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Todd J. Schwedt
investigator title: Principal Investigator
mesh term: Migraine Disorders
mesh term: Erenumab
sharing ipd: No
submitted: June 26, 2023
returned: July 21, 2023