<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/NCT04452929</url>
  </required_header>
  <id_info>
    <org_study_id>CGRP2020</org_study_id>
    <nct_id>NCT04452929</nct_id>
  </id_info>
  <brief_title>The Effect of Anti-calcitonin Gene-related Peptide (CGRP) Receptor Antibodies on the Headache Inducing Properties of CGRP and Cilostazol in Migraine Patients</brief_title>
  <official_title>The Effect of Anti-calcitonin Gene-related Peptide (CGRP) Receptor Antibodies on the Headache Inducing Properties of CGRP and Cilostazol in Migraine Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danish Headache Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Danish Headache Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, double-blind, placebo-controlled, parallel study to investigate the effect of&#xD;
      erenumab in calcitonin-gene related peptide and cilostazol experimental models of migraine in&#xD;
      humans. Followed by a 6-month open-label extension.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">February 2022</primary_completion_date>
  <phase>N/A</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>Randomized, double-blinded, placebo-controlled, parallel study followed by a 6-month open-label extension.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Migraine-like attack</measure>
    <time_frame>Before (-5 min) and after administration of (+12 hours) of experimental trigger</time_frame>
    <description>The incidence of migraine-like attack after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.&#xD;
A migraine-like attack is defined attack fulfilling either (i) or (ii):&#xD;
(i) Headache fulfilling criteria C and D for migraine without aura according to the International Headache Society criteria: C. Headache has at least two of the following characteristics: unilateral location; pulsating quality; moderate or severe pain intensity (moderate to severe pain intensity is considered ≥4 on verbal rating scale); aggravation by cough (in-hospital phase) or causing avoidance of routine physical activity (out-hospital phase); D. During headache at least one of the following: nausea and/or vomiting; photophobia and phonophobia; and (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Headache intensity</measure>
    <time_frame>Before (-5 min) and after administration of (+12 hours) of experimental trigger</time_frame>
    <description>Change in headache intensity after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.&#xD;
Headache intensity scores are measured by a numerical rating scale (NRS). It is a verbally declared scale from 0 to 10, where 0 is no pain; 10 is the worst pain imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemodynamics (superficial temporal artery)</measure>
    <time_frame>Before (-5 min) and after administration of (+90 minutes) of experimental trigger</time_frame>
    <description>Change in diameter (mm) of superficial temporal artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemodynamics (radial artery)</measure>
    <time_frame>Before (-5 min) and after administration of (+90 minutes) of experimental trigger</time_frame>
    <description>Change in diameter (mm) of radial artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropeptide plasma concentrations (CGRP)</measure>
    <time_frame>(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase</time_frame>
    <description>Change in plasma concentrations of calcitonin gene-related peptide (CGRP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.&#xD;
Change in plasma concentrations of calcitonin gene-related peptide during the open-label treatment phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropeptide plasma concentrations (VIP)</measure>
    <time_frame>(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase</time_frame>
    <description>Change in plasma concentrations of vasoactive intestinal peptide (VIP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.&#xD;
Change in plasma concentrations of vasoactive intestinal peptide (VIP) during the open-label treatment phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropeptide plasma concentrations (PACAP)</measure>
    <time_frame>(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase</time_frame>
    <description>Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.&#xD;
Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) during the open-label treatment phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Facial flushing</measure>
    <time_frame>Before (-5 min) and after administration of (+90 minutes) of experimental trigger</time_frame>
    <description>Change in facial skin flushing after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Facial temperature</measure>
    <time_frame>Before (-5 min) and after administration of (+90 minutes) of experimental trigger</time_frame>
    <description>Change in facial temperature after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Headache day</measure>
    <time_frame>Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase</time_frame>
    <description>Change in number of headache days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Migraine day</measure>
    <time_frame>Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase</time_frame>
    <description>Change in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>≥50% responder rate</measure>
    <time_frame>Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase</time_frame>
    <description>Proportion of participants with a ≥50% reduction in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Migraine</condition>
  <condition>Migraine Without Aura</condition>
  <condition>Migraine With Aura</condition>
  <arm_group>
    <arm_group_label>Randomized treatment phase: Erenumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Erenumab 140 mg single subcutaneous injection at baseline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized treatment phase: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline placebo single subcutaneous injection at baseline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open-label extension treatment phase: Erenumab</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Erenumab 140 mg monthly subcutaneous injection for six months after completion of the randomized, double-blinded, placebo-controlled study phase during the open-label extension</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erenumab</intervention_name>
    <description>Subcutaneous injection of 140 mg erenumab.</description>
    <arm_group_label>Open-label extension treatment phase: Erenumab</arm_group_label>
    <arm_group_label>Randomized treatment phase: Erenumab</arm_group_label>
    <other_name>Aimovig®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subcutaneous injection of saline placebo.</description>
    <arm_group_label>Randomized treatment phase: Placebo</arm_group_label>
    <other_name>Saline placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcitonin gene-related peptide</intervention_name>
    <description>Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.</description>
    <arm_group_label>Randomized treatment phase: Erenumab</arm_group_label>
    <arm_group_label>Randomized treatment phase: Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cilostazol</intervention_name>
    <description>Oral intake of 200 mg cilostazol.</description>
    <arm_group_label>Randomized treatment phase: Erenumab</arm_group_label>
    <arm_group_label>Randomized treatment phase: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with migraine with or without aura according to the International&#xD;
             Classification of Headache Disorders with a frequency of ≥4 migraine days per month&#xD;
&#xD;
          -  50-100 kg weight&#xD;
&#xD;
          -  Participants of childbearing potential must use safe contraception (birth control) or&#xD;
             be sexually abstinent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any other primary headache disorder according to the International Classification of&#xD;
             Headache Disorders except for tension-type headache&#xD;
&#xD;
          -  Any secondary headache disorder according to the International Classification of&#xD;
             Headache Disorders&#xD;
&#xD;
          -  Migraine attack during the preceding 48 hours on provocation day&#xD;
&#xD;
          -  Headache during the preceding 24 hours on provocation day&#xD;
&#xD;
          -  Treatment with monoclonal antibodies or participation in clinical trials with&#xD;
             monoclonal antibodies during the preceding year&#xD;
&#xD;
          -  Daily consumption of any other drug/medication than oral contraception (birth control)&#xD;
&#xD;
          -  Consumption of any other drug/medication later than four times the plasma half-time of&#xD;
             the drug on provocation day except for oral contraception&#xD;
&#xD;
          -  Pregnant or active breastfeeding participants&#xD;
&#xD;
          -  Any cardiovascular diseases including cerebrovascular disorders&#xD;
&#xD;
          -  Information in patient history or during physical examination indicating psychiatric&#xD;
             disorders or substance abuse&#xD;
&#xD;
          -  Information in patient history or during physical examination that the screening&#xD;
             physician deems relevant for participation in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thien P Do, MD</last_name>
    <role>Study Director</role>
    <affiliation>Danish Headache Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thien P Do, MD</last_name>
    <phone>004541414117</phone>
    <email>tdoo0001@regionh.dk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Danish Headache Center</name>
      <address>
        <city>Glostrup</city>
        <zip>2600</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thien P Do, MD</last_name>
      <phone>004541414117</phone>
      <email>tdoo0001@regionh.dk</email>
    </contact>
    <investigator>
      <last_name>Messoud Ashina, MD, PhD, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thien P Do, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Danish Headache Center</investigator_affiliation>
    <investigator_full_name>Messoud Ashina</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
    <mesh_term>Migraine without Aura</mesh_term>
    <mesh_term>Migraine with Aura</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcitonin</mesh_term>
    <mesh_term>Salmon calcitonin</mesh_term>
    <mesh_term>Cilostazol</mesh_term>
    <mesh_term>Calcitonin Gene-Related Peptide</mesh_term>
    <mesh_term>Erenumab</mesh_term>
    <mesh_term>Katacalcin</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/NCT04452929
org study id: CGRP2020
nct id: NCT04452929
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A randomized, double-blind, placebo-controlled, parallel study to investigate the effect of
      erenumab in calcitonin-gene related peptide and cilostazol experimental models of migraine in
      humans. Followed by a 6-month open-label extension.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, double-blinded, placebo-controlled, parallel study followed by a 6-month open-label extension.
primary purpose: Health Services Research
masking: Double (Participant, Investigator)
measure: Migraine-like attack
time frame: Before (-5 min) and after administration of (+12 hours) of experimental trigger
description: The incidence of migraine-like attack after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
A migraine-like attack is defined attack fulfilling either (i) or (ii):
(i) Headache fulfilling criteria C and D for migraine without aura according to the International Headache Society criteria: C. Headache has at least two of the following characteristics: unilateral location; pulsating quality; moderate or severe pain intensity (moderate to severe pain intensity is considered ≥4 on verbal rating scale); aggravation by cough (in-hospital phase) or causing avoidance of routine physical activity (out-hospital phase); D. During headache at least one of the following: nausea and/or vomiting; photophobia and phonophobia; and (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication).
measure: Headache intensity
time frame: Before (-5 min) and after administration of (+12 hours) of experimental trigger
description: Change in headache intensity after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
Headache intensity scores are measured by a numerical rating scale (NRS). It is a verbally declared scale from 0 to 10, where 0 is no pain; 10 is the worst pain imaginable.
measure: Hemodynamics (superficial temporal artery)
time frame: Before (-5 min) and after administration of (+90 minutes) of experimental trigger
description: Change in diameter (mm) of superficial temporal artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
measure: Hemodynamics (radial artery)
time frame: Before (-5 min) and after administration of (+90 minutes) of experimental trigger
description: Change in diameter (mm) of radial artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
measure: Neuropeptide plasma concentrations (CGRP)
time frame: (1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
description: Change in plasma concentrations of calcitonin gene-related peptide (CGRP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
Change in plasma concentrations of calcitonin gene-related peptide during the open-label treatment phase.
measure: Neuropeptide plasma concentrations (VIP)
time frame: (1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
description: Change in plasma concentrations of vasoactive intestinal peptide (VIP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
Change in plasma concentrations of vasoactive intestinal peptide (VIP) during the open-label treatment phase.
measure: Neuropeptide plasma concentrations (PACAP)
time frame: (1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
description: Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) during the open-label treatment phase.
measure: Facial flushing
time frame: Before (-5 min) and after administration of (+90 minutes) of experimental trigger
description: Change in facial skin flushing after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
measure: Facial temperature
time frame: Before (-5 min) and after administration of (+90 minutes) of experimental trigger
description: Change in facial temperature after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.
measure: Headache day
time frame: Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
description: Change in number of headache days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.
measure: Migraine day
time frame: Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
description: Change in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.
measure: ≥50% responder rate
time frame: Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
description: Proportion of participants with a ≥50% reduction in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.
arm group label: Randomized treatment phase: Erenumab
arm group type: Active Comparator
description: Erenumab 140 mg single subcutaneous injection at baseline
arm group label: Randomized treatment phase: Placebo
arm group type: Placebo Comparator
description: Saline placebo single subcutaneous injection at baseline
arm group label: Open-label extension treatment phase: Erenumab
arm group type: Other
description: Erenumab 140 mg monthly subcutaneous injection for six months after completion of the randomized, double-blinded, placebo-controlled study phase during the open-label extension
intervention type: Drug
intervention name: Erenumab
description: Subcutaneous injection of 140 mg erenumab.
arm group label: Open-label extension treatment phase: Erenumab
arm group label: Randomized treatment phase: Erenumab
other name: Aimovig®
intervention type: Drug
intervention name: Placebo
description: Subcutaneous injection of saline placebo.
arm group label: Randomized treatment phase: Placebo
other name: Saline placebo
intervention type: Drug
intervention name: Calcitonin gene-related peptide
description: Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.
arm group label: Randomized treatment phase: Erenumab
arm group label: Randomized treatment phase: Placebo
intervention type: Drug
intervention name: Cilostazol
description: Oral intake of 200 mg cilostazol.
arm group label: Randomized treatment phase: Erenumab
arm group label: Randomized treatment phase: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Thien P Do, MD
role: Study Director
affiliation: Danish Headache Center
last name: Thien P Do, MD
phone: 004541414117
email: tdoo0001@regionh.dk
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Danish Headache Center
investigator full name: Messoud Ashina
investigator title: Principal Investigator
mesh term: Migraine Disorders
mesh term: Migraine without Aura
mesh term: Migraine with Aura
mesh term: Headache
mesh term: Calcitonin
mesh term: Salmon calcitonin
mesh term: Cilostazol
mesh term: Calcitonin Gene-Related Peptide
mesh term: Erenumab
mesh term: Katacalcin
sharing ipd: No