<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/NCT03814226</url>
  </required_header>
  <id_info>
    <org_study_id>H-17011569</org_study_id>
    <nct_id>NCT03814226</nct_id>
  </id_info>
  <brief_title>PACAP-38 Infusion in Patients With Cluster Headache</brief_title>
  <official_title>The Effect of PACAP-38 Infusion in Inducing Headache in Patients With Cluster Headache</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danish Headache Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Danish Headache Center</source>
  <oversight_info>
    <has_dmc>No</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-blinded, two-way crossover study investigating the headache inducing&#xD;
      capabilities of PACAP-38 in patients with cluster headache. Forty-five patients (15 episodic&#xD;
      patients in cluster, 15, episodic patients in remission and 15 chronic cluster headache&#xD;
      patients) are expected to participate. Each patients will on two separate study days in a&#xD;
      randomized way receive an infusion of PACAP-38 and VIP over 20 minutes followed by an&#xD;
      observation period of 70 minutes. Blood samples for investigation of VIP, PACAP38; CGRP, NSE,&#xD;
      Histamine and Tryptase will be drawn at fixed time-points during experiment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">May 5, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2020</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Headache</measure>
    <time_frame>90 minutes</time_frame>
    <description>Difference in incidence of headache within 90 minutes of infusion between PACAP-38 infusion and VIP infusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE</measure>
    <time_frame>90 minutes</time_frame>
    <description>Changes in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE after infusion</measure>
    <time_frame>90 minutes</time_frame>
    <description>Difference in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE between patients with induced cluster headache and patients without headache</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline</measure>
    <time_frame>90 minutes</time_frame>
    <description>Difference in plasma/serum concentrations of the following markers at baseline: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE between patients with episodic cluster headache in remission, episodic cluster headache in cluster, and chronic cluster headache</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Headache intensity</measure>
    <time_frame>90 minutes</time_frame>
    <description>Difference in AUD for headache intensity scores (0-90 minutes)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to headache peak</measure>
    <time_frame>90 minutes</time_frame>
    <description>Difference in time to peak headache between PACAP-38 day and VIP day</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in mean arterial blood pressure</measure>
    <time_frame>90 minutes</time_frame>
    <description>Difference in area under the curve (AUC) for mean arterial pressure (based on systolic and diastolic measurements) and heart rate during experiment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE</measure>
    <time_frame>Baseline</time_frame>
    <description>Difference in serum/plasma levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline in patients who develop a cluster headache attack compared to those who do not</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Cluster Headache</condition>
  <arm_group>
    <arm_group_label>PACAP-38 infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>According to main hypothesis PACAP-38 is expected to induce headache. PACAP-38 causes marked vasodilation visible to investigator. PACAP38 (10 pmol/kg/min) is infused over 20 minutes, patients are observed before (15 minutes), during and after (70 minutes) infusion. Blood samples are drawn at fixed time-points.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>VIP infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>According to main hypothesis VIP is not expected to induce headache. VIP also causes marked vasodilation visible to investigator, which is why VIP is chosen as an active comparator. VIP (10 pmol/kg/min) is infused over 20 minutes. VIP is infused over 20 minutes, patients are observed before (15 minutes), during and after (70 minutes) infusion. Blood samples are drawn at fixed time-points.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Evaluation of headache inducing capabilities of PACAP38</intervention_name>
    <description>We wish to investigate the headache inducing capabilities of PACAP-38, a vasoactive peptide, over a 20 minute infusion. As PACAP-38 casues visible vasodilation, another vasoactive peptide, called VIP will be used as an active comparator.</description>
    <arm_group_label>PACAP-38 infusion</arm_group_label>
    <arm_group_label>VIP infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Episodic or chronic cluster headache according to international classification of&#xD;
             headache disorders&#xD;
&#xD;
          -  Age 18-65 years&#xD;
&#xD;
          -  Weight 50-100 kg&#xD;
&#xD;
          -  If women of childbearing potential, then must use safe contraceptives&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Episodic tension-type headache &gt; 15 days per month&#xD;
&#xD;
          -  Other primary headache disorders, except tension-type headache &lt; 5 days per month&#xD;
&#xD;
          -  Episodic cluster headache patients outside cluster must be completely headache free a&#xD;
             minimum of 8 hours prior to experiment&#xD;
&#xD;
          -  Episodic cluster headache patients in cluster and chronic cluster headache patients&#xD;
             must be completely headache free a minimum of 4 hours prior to experiment&#xD;
&#xD;
          -  Current or recent use (30 days) of injected or oral corticosteroids&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  A history or clinical signs of hypertension (BP &gt; 150mmHg systolic / 100mmHg&#xD;
             diastolic)&#xD;
&#xD;
          -  A history or clinical signs of hypotension (BP &lt;90 mmHg systolic / 50mmHg diastolic)&#xD;
&#xD;
          -  A history of cardiovascular or cerebrovascular disease&#xD;
&#xD;
          -  A history of psychiatric disease or substance abuse&#xD;
&#xD;
          -  A medical history or clinical signs of disease that according to investigator would&#xD;
             preclude participation in the study&#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>Messoud Ashina, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Danish Headache Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Agneta Snoer, MD</last_name>
    <phone>+ 45 26274040</phone>
    <email>agneta.henriette.snoer.02@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Luise Vollsen, MD</last_name>
    <phone>+45 25732284</phone>
    <email>luisevollsen@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Danish Headache Center</name>
      <address>
        <city>Glostrup</city>
        <zip>2620</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Agneta Snoer, MD</last_name>
      <phone>+ 45 26274040</phone>
      <email>agneta.henriette.snoer.02@regionh.dk</email>
    </contact>
    <investigator>
      <last_name>Anne Luise Vollesen, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Messoud Ashina, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>January 22, 2019</last_update_submitted>
  <last_update_submitted_qc>January 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Danish Headache Center</investigator_affiliation>
    <investigator_full_name>Agneta Snoer</investigator_full_name>
    <investigator_title>MD, PhD Student, Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cluster Headache</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pituitary Adenylate Cyclase-Activating Polypeptide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03814226
org study id: H-17011569
nct id: NCT03814226
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A randomized, double-blinded, two-way crossover study investigating the headache inducing
      capabilities of PACAP-38 in patients with cluster headache. Forty-five patients (15 episodic
      patients in cluster, 15, episodic patients in remission and 15 chronic cluster headache
      patients) are expected to participate. Each patients will on two separate study days in a
      randomized way receive an infusion of PACAP-38 and VIP over 20 minutes followed by an
      observation period of 70 minutes. Blood samples for investigation of VIP, PACAP38; CGRP, NSE,
      Histamine and Tryptase will be drawn at fixed time-points during experiment.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Investigator)
measure: Headache
time frame: 90 minutes
description: Difference in incidence of headache within 90 minutes of infusion between PACAP-38 infusion and VIP infusion
measure: Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE
time frame: 90 minutes
description: Changes in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE
measure: Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE after infusion
time frame: 90 minutes
description: Difference in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE between patients with induced cluster headache and patients without headache
measure: Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline
time frame: 90 minutes
description: Difference in plasma/serum concentrations of the following markers at baseline: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE between patients with episodic cluster headache in remission, episodic cluster headache in cluster, and chronic cluster headache
measure: Headache intensity
time frame: 90 minutes
description: Difference in AUD for headache intensity scores (0-90 minutes)
measure: Time to headache peak
time frame: 90 minutes
description: Difference in time to peak headache between PACAP-38 day and VIP day
measure: Change in mean arterial blood pressure
time frame: 90 minutes
description: Difference in area under the curve (AUC) for mean arterial pressure (based on systolic and diastolic measurements) and heart rate during experiment
measure: Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE
time frame: Baseline
description: Difference in serum/plasma levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline in patients who develop a cluster headache attack compared to those who do not
arm group label: PACAP-38 infusion
arm group type: Experimental
description: According to main hypothesis PACAP-38 is expected to induce headache. PACAP-38 causes marked vasodilation visible to investigator. PACAP38 (10 pmol/kg/min) is infused over 20 minutes, patients are observed before (15 minutes), during and after (70 minutes) infusion. Blood samples are drawn at fixed time-points.
arm group label: VIP infusion
arm group type: Active Comparator
description: According to main hypothesis VIP is not expected to induce headache. VIP also causes marked vasodilation visible to investigator, which is why VIP is chosen as an active comparator. VIP (10 pmol/kg/min) is infused over 20 minutes. VIP is infused over 20 minutes, patients are observed before (15 minutes), during and after (70 minutes) infusion. Blood samples are drawn at fixed time-points.
intervention type: Other
intervention name: Evaluation of headache inducing capabilities of PACAP38
description: We wish to investigate the headache inducing capabilities of PACAP-38, a vasoactive peptide, over a 20 minute infusion. As PACAP-38 casues visible vasodilation, another vasoactive peptide, called VIP will be used as an active comparator.
arm group label: PACAP-38 infusion
arm group label: VIP infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Messoud Ashina, Professor
role: Principal Investigator
affiliation: Danish Headache Center
last name: Agneta Snoer, MD
phone: + 45 26274040
email: agneta.henriette.snoer.02@regionh.dk
last name: Luise Vollsen, MD
phone: +45 25732284
email: luisevollsen@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Danish Headache Center
investigator full name: Agneta Snoer
investigator title: MD, PhD Student, Investigator
mesh term: Cluster Headache
mesh term: Headache
mesh term: Pituitary Adenylate Cyclase-Activating Polypeptide
sharing ipd: Undecided