<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/NCT04417361</url>
  </required_header>
  <id_info>
    <org_study_id>19-29340</org_study_id>
    <secondary_id>P0541760</secondary_id>
    <nct_id>NCT04417361</nct_id>
  </id_info>
  <brief_title>Galcanezumab for Vestibular Migraine</brief_title>
  <official_title>A Pilot Trial of Galcanezumab for Vestibular Migraine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</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>
      Vestibular migraine (VM) has been recognized a distinct subtype of migraine that causes&#xD;
      dizziness as the predominant symptom. Criteria for diagnosis have been adopted by the Barany&#xD;
      Society. Previous epidemiological research from the investigators has shown that VM affects&#xD;
      2.7% of the adult population of the United States. Yet, despite its high prevalence, there is&#xD;
      very little data upon which to guide treatment decisions. A Cochrane review in 2015 concluded&#xD;
      that there were no placebo controlled trials in VM, and none have been done since then. The&#xD;
      investigators recently developed and validated a patient reported outcome tool for VM called&#xD;
      VM-PATHI (VM- Patient Assessment Tool and Handicap Inventory). Anecdotal evidence suggests&#xD;
      that CGRP antagonists, such as Galcanezumab, may be effective in reducing or eliminating&#xD;
      symptoms in VM. Therefore, the investigators propose a pilot study of changes in VM-PATHI&#xD;
      scores, comparing active treatment (Galcanezumab) to placebo arms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vestibular migraine (VM) is a distinct subtype of migraine that causes episodic&#xD;
      vertigo/dizziness, sometimes with headache, and sometimes without. However, unlike&#xD;
      traditional migraines, patients generally seek out care because of dizziness, and not because&#xD;
      of headache. Therefore, these patients are cared for by a variety of providers who treat&#xD;
      dizziness, including otolaryngologists and neurologists. Lifetime prevalence of VM in the&#xD;
      general population is estimated to be 2.7%, and at least 10% of patients in a tertiary care&#xD;
      vestibular clinic have VM. Furthermore, VM has been shown to decrease quality of life in&#xD;
      multiple domains, including overall health, mental health, and emotional health. Since&#xD;
      testing and imaging are usually normal, diagnosis can only be made on clinical grounds.&#xD;
      Recently, consensus criteria for diagnosis was published by the Barany Society and the&#xD;
      International Classification of Headache Disorders.&#xD;
&#xD;
      Galcanezumab is a calcitonin gene related peptide (CGRP) antagonist that has been approved by&#xD;
      the FDA for treatment of episodic and chronic migraine. Its effects with regards to VM have&#xD;
      not been formally studied. However, there is ample evidence to suggest that aberrant&#xD;
      trigeminovascular inflammation may be integral to the pathophysiology of VM, similar to&#xD;
      migraine in general.&#xD;
&#xD;
      This pilot study will be a single center, randomized double-blinded placebo-controlled trial&#xD;
      comparing galcanezumab to placebo for treatment of VM. Screening data will be reviewed to&#xD;
      determine subject eligibility. Participants who meet all inclusion criteria and none of the&#xD;
      exclusion criteria will be entered into the study. Participants in the galcanezumab arm will&#xD;
      receive 240 mg via subcutaneous injection with a pre-loaded syringe at month 1, followed by&#xD;
      120 mg at month 2, and 120 mg at month 3. Those in the placebo arms will receive subcutaneous&#xD;
      injections at the same time intervals of placebo. Randomization will occur through the&#xD;
      hospital research pharmacy. Allocation concealment will be ensured; study participants will&#xD;
      be given an envelope from a folder of sequentially ordered identical envelopes that will&#xD;
      contain study instructions and the allocated drug. The master file linking study ID with&#xD;
      allocation will be created by a third party and kept secret until after data analysis is&#xD;
      complete. This will ensure that both providers and participants are adequately blinded.&#xD;
      Blocking will be used in increments of 10 subjects to ensure equitable distribution of&#xD;
      subjects into the two treatment arms. In addition, stratification by sex and definite versus&#xD;
      probable vestibular migraine status will be used to ensure equal allocation. Total duration&#xD;
      of subject participation will be five months. Total duration of the study is expected to be 2&#xD;
      years.&#xD;
&#xD;
      Data collection will be performed by the clinical research coordinator during each study&#xD;
      visit. This data will be entered into the REDCap database by the research coordinator. VM-&#xD;
      Patient Assessment Tool and Handicap Inventory (VM-PATHI), dizziness handicap inventory&#xD;
      (DHI), General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9),&#xD;
      Patient-Reported Outcomes Measurement Information System Short Form (PROMIS SF) v1.1- Global&#xD;
      Health, and Headache Impact Test-6 (HIT-6) will be administered electronically via REDCap to&#xD;
      the subject during the study visit.&#xD;
&#xD;
      There will be no stopping rules for this trial, given the short duration of the study. Each&#xD;
      adverse effect and serious adverse effect will be reviewed by the data safety monitoring&#xD;
      team, and subjects may be unblinded and/or the study will be stopped early for serious safety&#xD;
      concerns.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 18, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</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>Parallel Assignment</intervention_model>
    <intervention_model_description>The study drug will be administered with a subcutaneous injection of galcanezumab or placebo. The first dose (at month 1) will be a loading dose of two injections, or 240 mg in total. After that, at month 2 and month 3, each participant will get either a subcutaneous injection of galcanezumab 120 mg or placebo. The injections will be with a pre-loaded syringe containing either galcanezumab or placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The following study procedures will be in place to ensure double-blind administration of study treatments. Access to the randomization code will be strictly controlled and this will reside with our pharmacist, who will not be blinded. All members of the clinical team and biostatistician will be blinded. Packaging and labeling of test and control treatments will be identical to maintain the blind. Each participant will be given an identical study packet, containing their assigned drug and study information. The study blind will be broken on completion of the clinical study and after the study database has been locked. Investigators will be made aware of their participants' treatment designations only after all the data has been collected and analyzed. During the study, the blind may be broken only in emergencies when knowledge of the participant's treatment group is necessary for further clinical management.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in VM-PATHI (Vestibular Migraine-Patient Assessment Tool and Handicap Inventory) Score from Baseline to Month 4</measure>
    <time_frame>Change between baseline (month 0) and after treatment (month 4)</time_frame>
    <description>This is a recently developed and validated outcome measure for vestibular migraine from the investigators. It has been shown to be highly reliable and valid, and responsive to treatment changes. At this point, it is the only disease specific outcome measure for vestibular migraine. Scores are between 0 and 100, with 100 indicating higher levels of disease related suffering.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Number of Definitive Dizzy Days for Participants Measured Daily from Baseline to Month 4 via Text Message</measure>
    <time_frame>Change between baseline (month 0) and after treatment (month 4)</time_frame>
    <description>Participants will receive a daily text message to rate their dizziness from 0 (no dizziness), 1 (mild dizziness), 2 (moderate dizziness), and 3 (severe dizziness). A score of 2 or higher will count as a definitive dizzy day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Response Rates as Defined by Percentage Reduction in Definitive Dizzy Days via Text Message from Baseline to Month 4</measure>
    <time_frame>Change between baseline (month 0) to after treatment (month 4)</time_frame>
    <description>Response rates will be measured by the percentage of participants in each arm experiencing a 100%, 75%, 50%, 25%, 0% reduction in definitive dizzy days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Dizziness Handicap Inventory Score from Baseline to Month 4</measure>
    <time_frame>Change between baseline (month 0) to after treatment (month 4)</time_frame>
    <description>This is the most widely used measure of dizziness severity, and consists of 25 questions. Questions ask about problems related to dizziness, and are scored as no (0 points), sometimes (2 points), or always (4 points). Total score is between 0 and 100, with higher scores indicating more disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient-Reported Outcomes Measurement Information System Short Form (PROMIS SF) v1.2- Global Health Scores</measure>
    <time_frame>Change between baseline (month 0) to after treatment (month 4)</time_frame>
    <description>There are 10 questions on this quality of life measure, each with a score of 1-5. Higher scores correspond to a greater extent of the concept measured (e.g., more fatigue). Two summed scores are generated, one for global mental health (question #3, 6, 7, 8) and one for global physical health (question #2, 4, 5, 10). The remaining 2 questions are analyzed separately.&#xD;
Summed scores for physical health and mental health are converted into T-score values using the &quot;HealthMeasures Scoring Service&quot; available online. T-scores for physical health and mental health can be grouped into 5 categories based on the responses to question #1: &quot;In general, would you say your health is excellent, very good, good, fair, or poor?&quot; The cut points for each category is determined by calculating the midpoint between 2 adjacent means. For example, if the mean mental health T-score for &quot;Excellent&quot; is 61 and the mean T-score for &quot;Very Good&quot; is 51, then the cut point for these categories would be 56.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Vestibular Migraine</condition>
  <arm_group>
    <arm_group_label>Galcanezumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The galcanezumab arm will self-administer a subcutaneous injection of galcanezumab. The first dose (at month 1) will be a loading dose of two injections, or 240 mg in total. After that, at month 2 and month 3, each participant will receive an injection of galcanezumab 120 mg. The injections will be with a pre-loaded syringe containing galcanezumab.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo arm will self-administer a subcutaneous injection of placebo. The first dose (at month 1) will be a loading dose of two injections, or 240 mg in total. After that, at month 2 and month 3, each participant will receive an injection of placebo 120 mg. The injections will be with a pre-loaded syringe containing placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Galcanezumab Prefilled Syringe</intervention_name>
    <description>Galcanezumab will be supplied in preloaded syringes, each with a dose of 120 mg. Participants will first receive the first month's supply (240 mg) at study visit 2, and then will receive a two month supply at study visit 3. So, at study visit 2 and 3, each participant will get two pre-filled syringes.</description>
    <arm_group_label>Galcanezumab</arm_group_label>
    <other_name>Emgality</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will be supplied in preloaded syringes, each with a dose of 120 mg. Participants will first receive the first month's supply (240 mg) at study visit 2, and then will receive a two month supply at study visit 3. So, at study visit 2 and 3, each participant will get two pre-filled syringes.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female aged 18 to 75 years of age at Study Visit 1.&#xD;
&#xD;
          2. Documentation of a vestibular migraine or probable vestibular migraine diagnosis&#xD;
             according to the following criteria determined by the Barany Society:&#xD;
&#xD;
               -  Vestibular migraine&#xD;
&#xD;
                    -  A: At least 5 episodes with vestibular symptoms of moderate or severe&#xD;
                       intensity, lasting 5 min to 72 hours&#xD;
&#xD;
                    -  B: Current or previous history of migraine with or without aura according to&#xD;
                       the International Classification of Headache Disorders (ICHD)&#xD;
&#xD;
                    -  C: One or more migraine features with at least 50% of the vestibular&#xD;
                       episodes:&#xD;
&#xD;
                         -  Headache with at least two of the following characteristics: one sided&#xD;
                            location, pulsating quality, moderate or severe pain intensity,&#xD;
                            aggravation by routine physical activity&#xD;
&#xD;
                         -  Photophobia and phonophobia&#xD;
&#xD;
                         -  Visual aura&#xD;
&#xD;
                    -  D: Not better accounted for by another vestibular or ICHD diagnosis&#xD;
&#xD;
               -  Probable vestibular migraine&#xD;
&#xD;
                    -  At least 5 episodes with vestibular symptoms of moderate or severe&#xD;
                       intensity, lasting 5 min to 72 hours&#xD;
&#xD;
                    -  Only one of the criteria B and C for vestibular migraine is fulfilled&#xD;
                       (migraine history or migraine features during the episode)&#xD;
&#xD;
                    -  Not better accounted for by another vestibular or ICHD diagnosis&#xD;
&#xD;
          3. Written informed consent obtained from subject and ability for subject to comply with&#xD;
             the requirements of the study.&#xD;
&#xD;
          4. Baseline and Study Visit 2 VM-PATHI score &gt; 25&#xD;
&#xD;
          5. Baseline (month 0 to 1) definite dizzy days &gt; 4&#xD;
&#xD;
          6. Fluency in English&#xD;
&#xD;
          7. 80% adherence or better to daily text message during baseline phase&#xD;
&#xD;
          8. Written informed consent&#xD;
&#xD;
          9. Access to email, and cell phone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant, breastfeeding, or unwilling to use approved form of birth control during&#xD;
             participation in the study.&#xD;
&#xD;
          2. Presence of a condition or abnormality that in the opinion of the Investigator would&#xD;
             compromise the safety of the patient or the quality of the data.&#xD;
&#xD;
          3. Allergy to galcanezumab&#xD;
&#xD;
          4. Prior treatment with galcanezumab&#xD;
&#xD;
          5. History of ear surgery (other than ear tubes)&#xD;
&#xD;
          6. Other vestibular diagnosis (excluding treated Benign Paroxysmal Positional Vertigo-&#xD;
             BPPV). This includes Meniere's disease, superior canal dehiscence syndrome, vestibular&#xD;
             neuritis, persistent postural perceptual dizziness, unilateral or bilateral vestibular&#xD;
             loss, cerebellar or brainstem disease, multiple sclerosis, or Mal de Debarquement.&#xD;
&#xD;
          7. Failure of treatment with &gt; 4 prophylactic migraine medications&#xD;
&#xD;
          8. Prior or current treatment with a CGRP medication&#xD;
&#xD;
          9. Pregnant/breastfeeding if female&#xD;
&#xD;
         10. History of serious medical or psychiatric disease, at the discretion of the treating&#xD;
             physician (including significant coronary artery disease, peripheral vascular disease,&#xD;
             cerebrovascular disease, kidney disease, liver disease, Raynaud's disease,&#xD;
             uncontrolled psychiatric disease or past psychiatric hospitalization)&#xD;
&#xD;
         11. History of mania, psychosis, or suicidal ideations&#xD;
&#xD;
         12. Ok if on up to 2 migraine prophylactic medications (prescribed for that purpose), dose&#xD;
             must be stable for 2 months prior to study start.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey D Sharon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jeffrey D Sharon, MD</last_name>
    <phone>(415) 353-2757</phone>
    <email>jeffrey.sharon@ucsf.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maxwell Hum, BS</last_name>
    <email>maxwell.hum@ucsf.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCSF Medical Center at Mount Zion</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeffrey D Sharon, MD</last_name>
      <phone>415-353-2757</phone>
      <email>jeffrey.sharon@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Jeffrey D Sharon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015 Jan;36(1):133-8. doi: 10.1097/MAO.0000000000000596.</citation>
    <PMID>25251304</PMID>
  </reference>
  <reference>
    <citation>Formeister EJ, Rizk HG, Kohn MA, Sharon JD. The Epidemiology of Vestibular Migraine: A Population-based Survey Study. Otol Neurotol. 2018 Sep;39(8):1037-1044. doi: 10.1097/MAO.0000000000001900.</citation>
    <PMID>30020261</PMID>
  </reference>
  <reference>
    <citation>Lempert T, Olesen J, Furman J, Waterston J, Seemungal B, Carey J, Bisdorff A, Versino M, Evers S, Newman-Toker D. Vestibular migraine: diagnostic criteria. J Vestib Res. 2012;22(4):167-72. doi: 10.3233/VES-2012-0453.</citation>
    <PMID>23142830</PMID>
  </reference>
  <reference>
    <citation>Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013 Jul;12(7):706-15. doi: 10.1016/S1474-4422(13)70107-8.</citation>
    <PMID>23769597</PMID>
  </reference>
  <reference>
    <citation>Vass Z, Dai CF, Steyger PS, Jancso G, Trune DR, Nuttall AL. Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries. Neuroscience. 2004;124(4):919-27. doi: 10.1016/j.neuroscience.2003.12.030.</citation>
    <PMID>15026132</PMID>
  </reference>
  <reference>
    <citation>Salviz M, Yuce T, Acar H, Karatas A, Acikalin RM. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016 Jan;126(1):169-74. doi: 10.1002/lary.25445. Epub 2015 Jul 30.</citation>
    <PMID>26228645</PMID>
  </reference>
  <reference>
    <citation>Reploeg MD, Goebel JA. Migraine-associated dizziness: patient characteristics and management options. Otol Neurotol. 2002 May;23(3):364-71. doi: 10.1097/00129492-200205000-00024.</citation>
    <PMID>11981397</PMID>
  </reference>
  <reference>
    <citation>Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012 Jan-Feb;33(1):121-7. doi: 10.1016/j.amjoto.2011.04.010. Epub 2011 Jun 24.</citation>
    <PMID>21704423</PMID>
  </reference>
  <reference>
    <citation>Lepcha A, Amalanathan S, Augustine AM, Tyagi AK, Balraj A. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014 Nov;271(11):2931-6. doi: 10.1007/s00405-013-2786-4. Epub 2013 Oct 29.</citation>
    <PMID>24166742</PMID>
  </reference>
  <reference>
    <citation>Maldonado Fernandez M, Birdi JS, Irving GJ, Murdin L, Kivekas I, Strupp M. Pharmacological agents for the prevention of vestibular migraine. Cochrane Database Syst Rev. 2015 Jun 21;2015(6):CD010600. doi: 10.1002/14651858.CD010600.pub2.</citation>
    <PMID>26093662</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vestibular migraine</keyword>
  <keyword>galcanezumab</keyword>
  <keyword>clinical trial</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>
  <!-- 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/NCT04417361
org study id: 19-29340
secondary id: P0541760
nct id: NCT04417361
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Vestibular migraine (VM) has been recognized a distinct subtype of migraine that causes
      dizziness as the predominant symptom. Criteria for diagnosis have been adopted by the Barany
      Society. Previous epidemiological research from the investigators has shown that VM affects
      2.7% of the adult population of the United States. Yet, despite its high prevalence, there is
      very little data upon which to guide treatment decisions. A Cochrane review in 2015 concluded
      that there were no placebo controlled trials in VM, and none have been done since then. The
      investigators recently developed and validated a patient reported outcome tool for VM called
      VM-PATHI (VM- Patient Assessment Tool and Handicap Inventory). Anecdotal evidence suggests
      that CGRP antagonists, such as Galcanezumab, may be effective in reducing or eliminating
      symptoms in VM. Therefore, the investigators propose a pilot study of changes in VM-PATHI
      scores, comparing active treatment (Galcanezumab) to placebo arms.
Vestibular migraine (VM) is a distinct subtype of migraine that causes episodic
      vertigo/dizziness, sometimes with headache, and sometimes without. However, unlike
      traditional migraines, patients generally seek out care because of dizziness, and not because
      of headache. Therefore, these patients are cared for by a variety of providers who treat
      dizziness, including otolaryngologists and neurologists. Lifetime prevalence of VM in the
      general population is estimated to be 2.7%, and at least 10% of patients in a tertiary care
      vestibular clinic have VM. Furthermore, VM has been shown to decrease quality of life in
      multiple domains, including overall health, mental health, and emotional health. Since
      testing and imaging are usually normal, diagnosis can only be made on clinical grounds.
      Recently, consensus criteria for diagnosis was published by the Barany Society and the
      International Classification of Headache Disorders.

      Galcanezumab is a calcitonin gene related peptide (CGRP) antagonist that has been approved by
      the FDA for treatment of episodic and chronic migraine. Its effects with regards to VM have
      not been formally studied. However, there is ample evidence to suggest that aberrant
      trigeminovascular inflammation may be integral to the pathophysiology of VM, similar to
      migraine in general.

      This pilot study will be a single center, randomized double-blinded placebo-controlled trial
      comparing galcanezumab to placebo for treatment of VM. Screening data will be reviewed to
      determine subject eligibility. Participants who meet all inclusion criteria and none of the
      exclusion criteria will be entered into the study. Participants in the galcanezumab arm will
      receive 240 mg via subcutaneous injection with a pre-loaded syringe at month 1, followed by
      120 mg at month 2, and 120 mg at month 3. Those in the placebo arms will receive subcutaneous
      injections at the same time intervals of placebo. Randomization will occur through the
      hospital research pharmacy. Allocation concealment will be ensured; study participants will
      be given an envelope from a folder of sequentially ordered identical envelopes that will
      contain study instructions and the allocated drug. The master file linking study ID with
      allocation will be created by a third party and kept secret until after data analysis is
      complete. This will ensure that both providers and participants are adequately blinded.
      Blocking will be used in increments of 10 subjects to ensure equitable distribution of
      subjects into the two treatment arms. In addition, stratification by sex and definite versus
      probable vestibular migraine status will be used to ensure equal allocation. Total duration
      of subject participation will be five months. Total duration of the study is expected to be 2
      years.

      Data collection will be performed by the clinical research coordinator during each study
      visit. This data will be entered into the REDCap database by the research coordinator. VM-
      Patient Assessment Tool and Handicap Inventory (VM-PATHI), dizziness handicap inventory
      (DHI), General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9),
      Patient-Reported Outcomes Measurement Information System Short Form (PROMIS SF) v1.1- Global
      Health, and Headache Impact Test-6 (HIT-6) will be administered electronically via REDCap to
      the subject during the study visit.

      There will be no stopping rules for this trial, given the short duration of the study. Each
      adverse effect and serious adverse effect will be reviewed by the data safety monitoring
      team, and subjects may be unblinded and/or the study will be stopped early for serious safety
      concerns.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study drug will be administered with a subcutaneous injection of galcanezumab or placebo. The first dose (at month 1) will be a loading dose of two injections, or 240 mg in total. After that, at month 2 and month 3, each participant will get either a subcutaneous injection of galcanezumab 120 mg or placebo. The injections will be with a pre-loaded syringe containing either galcanezumab or placebo.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The following study procedures will be in place to ensure double-blind administration of study treatments. Access to the randomization code will be strictly controlled and this will reside with our pharmacist, who will not be blinded. All members of the clinical team and biostatistician will be blinded. Packaging and labeling of test and control treatments will be identical to maintain the blind. Each participant will be given an identical study packet, containing their assigned drug and study information. The study blind will be broken on completion of the clinical study and after the study database has been locked. Investigators will be made aware of their participants' treatment designations only after all the data has been collected and analyzed. During the study, the blind may be broken only in emergencies when knowledge of the participant's treatment group is necessary for further clinical management.
measure: Change in VM-PATHI (Vestibular Migraine-Patient Assessment Tool and Handicap Inventory) Score from Baseline to Month 4
time frame: Change between baseline (month 0) and after treatment (month 4)
description: This is a recently developed and validated outcome measure for vestibular migraine from the investigators. It has been shown to be highly reliable and valid, and responsive to treatment changes. At this point, it is the only disease specific outcome measure for vestibular migraine. Scores are between 0 and 100, with 100 indicating higher levels of disease related suffering.
measure: Change in Number of Definitive Dizzy Days for Participants Measured Daily from Baseline to Month 4 via Text Message
time frame: Change between baseline (month 0) and after treatment (month 4)
description: Participants will receive a daily text message to rate their dizziness from 0 (no dizziness), 1 (mild dizziness), 2 (moderate dizziness), and 3 (severe dizziness). A score of 2 or higher will count as a definitive dizzy day.
measure: Change in Response Rates as Defined by Percentage Reduction in Definitive Dizzy Days via Text Message from Baseline to Month 4
time frame: Change between baseline (month 0) to after treatment (month 4)
description: Response rates will be measured by the percentage of participants in each arm experiencing a 100%, 75%, 50%, 25%, 0% reduction in definitive dizzy days.
measure: Change in Dizziness Handicap Inventory Score from Baseline to Month 4
time frame: Change between baseline (month 0) to after treatment (month 4)
description: This is the most widely used measure of dizziness severity, and consists of 25 questions. Questions ask about problems related to dizziness, and are scored as no (0 points), sometimes (2 points), or always (4 points). Total score is between 0 and 100, with higher scores indicating more disability.
measure: Change in Patient-Reported Outcomes Measurement Information System Short Form (PROMIS SF) v1.2- Global Health Scores
time frame: Change between baseline (month 0) to after treatment (month 4)
description: There are 10 questions on this quality of life measure, each with a score of 1-5. Higher scores correspond to a greater extent of the concept measured (e.g., more fatigue). Two summed scores are generated, one for global mental health (question #3, 6, 7, 8) and one for global physical health (question #2, 4, 5, 10). The remaining 2 questions are analyzed separately.
Summed scores for physical health and mental health are converted into T-score values using the "HealthMeasures Scoring Service" available online. T-scores for physical health and mental health can be grouped into 5 categories based on the responses to question #1: "In general, would you say your health is excellent, very good, good, fair, or poor?" The cut points for each category is determined by calculating the midpoint between 2 adjacent means. For example, if the mean mental health T-score for "Excellent" is 61 and the mean T-score for "Very Good" is 51, then the cut point for these categories would be 56.
arm group label: Galcanezumab
arm group type: Experimental
description: The galcanezumab arm will self-administer a subcutaneous injection of galcanezumab. The first dose (at month 1) will be a loading dose of two injections, or 240 mg in total. After that, at month 2 and month 3, each participant will receive an injection of galcanezumab 120 mg. The injections will be with a pre-loaded syringe containing galcanezumab.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo arm will self-administer a subcutaneous injection of placebo. The first dose (at month 1) will be a loading dose of two injections, or 240 mg in total. After that, at month 2 and month 3, each participant will receive an injection of placebo 120 mg. The injections will be with a pre-loaded syringe containing placebo.
intervention type: Drug
intervention name: Galcanezumab Prefilled Syringe
description: Galcanezumab will be supplied in preloaded syringes, each with a dose of 120 mg. Participants will first receive the first month's supply (240 mg) at study visit 2, and then will receive a two month supply at study visit 3. So, at study visit 2 and 3, each participant will get two pre-filled syringes.
arm group label: Galcanezumab
other name: Emgality
intervention type: Drug
intervention name: Placebo
description: Placebo will be supplied in preloaded syringes, each with a dose of 120 mg. Participants will first receive the first month's supply (240 mg) at study visit 2, and then will receive a two month supply at study visit 3. So, at study visit 2 and 3, each participant will get two pre-filled syringes.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jeffrey D Sharon, MD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Jeffrey D Sharon, MD
phone: (415) 353-2757
email: jeffrey.sharon@ucsf.edu
last name: Maxwell Hum, BS
email: maxwell.hum@ucsf.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
citation: Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015 Jan;36(1):133-8. doi: 10.1097/MAO.0000000000000596.
PMID: 25251304
citation: Formeister EJ, Rizk HG, Kohn MA, Sharon JD. The Epidemiology of Vestibular Migraine: A Population-based Survey Study. Otol Neurotol. 2018 Sep;39(8):1037-1044. doi: 10.1097/MAO.0000000000001900.
PMID: 30020261
citation: Lempert T, Olesen J, Furman J, Waterston J, Seemungal B, Carey J, Bisdorff A, Versino M, Evers S, Newman-Toker D. Vestibular migraine: diagnostic criteria. J Vestib Res. 2012;22(4):167-72. doi: 10.3233/VES-2012-0453.
PMID: 23142830
citation: Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013 Jul;12(7):706-15. doi: 10.1016/S1474-4422(13)70107-8.
PMID: 23769597
citation: Vass Z, Dai CF, Steyger PS, Jancso G, Trune DR, Nuttall AL. Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries. Neuroscience. 2004;124(4):919-27. doi: 10.1016/j.neuroscience.2003.12.030.
PMID: 15026132
citation: Salviz M, Yuce T, Acar H, Karatas A, Acikalin RM. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016 Jan;126(1):169-74. doi: 10.1002/lary.25445. Epub 2015 Jul 30.
PMID: 26228645
citation: Reploeg MD, Goebel JA. Migraine-associated dizziness: patient characteristics and management options. Otol Neurotol. 2002 May;23(3):364-71. doi: 10.1097/00129492-200205000-00024.
PMID: 11981397
citation: Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012 Jan-Feb;33(1):121-7. doi: 10.1016/j.amjoto.2011.04.010. Epub 2011 Jun 24.
PMID: 21704423
citation: Lepcha A, Amalanathan S, Augustine AM, Tyagi AK, Balraj A. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014 Nov;271(11):2931-6. doi: 10.1007/s00405-013-2786-4. Epub 2013 Oct 29.
PMID: 24166742
citation: Maldonado Fernandez M, Birdi JS, Irving GJ, Murdin L, Kivekas I, Strupp M. Pharmacological agents for the prevention of vestibular migraine. Cochrane Database Syst Rev. 2015 Jun 21;2015(6):CD010600. doi: 10.1002/14651858.CD010600.pub2.
PMID: 26093662
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Erenumab
sharing ipd: No