<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/NCT03806595</url>
  </required_header>
  <id_info>
    <org_study_id>H18-03801</org_study_id>
    <nct_id>NCT03806595</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Intranasal Lidocaine in Acute Management of Pediatric Migraine</brief_title>
  <official_title>A Pilot Study of Intranasal Lidocaine in Acute Management of Pediatric Migraine and Migraine-like Headache: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of British Columbia</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Headaches in children are very common and are a source of significant distress for the&#xD;
      patient and their family. Migraines are the most common headache disorder in children and are&#xD;
      associated with episodic pain and other symptoms such as nausea and sensitivity to light and&#xD;
      sound that can impair a child's ability to participate in daily activities and lead to missed&#xD;
      school or parental missed work. When home treatment fails to relieve symptoms, children often&#xD;
      seek care in the emergency department (ED) where a limited number of treatment options exist;&#xD;
      while largely effective, these rescue treatments currently all require needle insertion of an&#xD;
      intravenous line, take time to administer, result in prolonged ED stays, and have potential&#xD;
      unpleasant side effects. In adult patients, a number of studies suggest that lidocaine, a&#xD;
      local anesthetic administered intranasally, may provide relief of migraine and migraine-like&#xD;
      headache pain in minutes. This approach has the benefit of working quickly, not requiring a&#xD;
      needle, and having fewer side effects as the medication acts locally on nerves in the nose.&#xD;
      Intranasal lidocaine has not yet been studied in children for this purpose. This study will&#xD;
      compare the use of intranasal lidocaine to placebo. The goal of this pilot study is to&#xD;
      provide information to inform the sample size calculation for the definitive randomized&#xD;
      controlled trial that will aim to measure the efficacy of intranasal lidocaine as an&#xD;
      analgesic option for children age 7 years and older who present to the Pediatric ED with a&#xD;
      chief complaint of migraine or post traumatic headache with migraine-like features. Secondary&#xD;
      objectives will be to report on the frequency and severity of rebound headache between the&#xD;
      two treatment groups, adverse events of the study drug, as well as the impact on healthcare&#xD;
      utilization measures.The investigators hypothesize that children receiving intranasal&#xD;
      lidocaine will have faster and more effective pain recovery compared to children receiving&#xD;
      placebo and will be less likely to require the standard therapy for migraine headache. Given&#xD;
      very few side effects reported in adult studies and the relatively benign nature of those&#xD;
      reported, the investigators do not expect any major safety concerns in the study. It is also&#xD;
      hypothesized that intranasal lidocaine will lead to shorter ED visits, thus reducing use of&#xD;
      staff and hospital resources and saving money for the healthcare system as a whole.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 3, 2019</start_date>
  <completion_date type="Actual">December 3, 2020</completion_date>
  <primary_completion_date type="Actual">December 3, 2020</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in migraine pain</measure>
    <time_frame>Pain scores will be measured at 30 and 60 minutes post intranasal administration of either the study drug or placebo.</time_frame>
    <description>The primary outcome measure will be the proportion of subjects with numeric pain scores of &lt; 4 out of 10 on a verbal rating scale (range 0 -10 with increasing severity, i.e. 0 = no pain and 10 = most severe pain).Treatment success is defined as a score of 3 or less at the two time points. This will be recorded for each patient during the study timeframe, until study completion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rebound headache</measure>
    <time_frame>Pain scores will be recorded at 60 minutes, 24 hours, and within 48-72 hours post intranasal therapy.</time_frame>
    <description>Proportion of patients with rebound headache (i.e. headache with pain score of greater than or equal to 4 out of 10 on a verbal rating scale; range 0 -10 with increasing severity, i.e. 0 = no pain and 10 = most severe pain). This will be recorded for each patient at the visit of interest during the study timeframe, until study completion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency department length of stay</measure>
    <time_frame>The emergency department length of stay will be ascertained from the medical record within 24 hours of the participant's visit.</time_frame>
    <description>Number of hours in the Emergency Department from time of registration to time of discharge or admission to hospital for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants discharged vs. admitted from the emergency department (emergency department disposition)</measure>
    <time_frame>Disposition will be ascertained from the medical record within 24 hours of the participant's ED visit.</time_frame>
    <description>Disposition of the patient from the emergency department for the visit of interest only, i.e. discharge home, hospital admission. This will be recorded for each patient during the study timeframe, until study completion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with a return visit to the emergency department within 72 hours of discharge.</measure>
    <time_frame>Within 3 days from index visit.</time_frame>
    <description>Returns to the emergency department for similar complaints of migraine headache or posttraumatic headache with migraine like features.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Migraine in Children</condition>
  <condition>Posttraumatic Headache</condition>
  <arm_group>
    <arm_group_label>Intranasal lidocaine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1mL of lidocaine 2% will be instilled in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intranasal normal saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1mL of saline 0.9% will be instilled in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine 2% Injectable Solution</intervention_name>
    <description>The Barre method of intranasal administration will be used to instil 1mL of lidocaine 2% in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.</description>
    <arm_group_label>Intranasal lidocaine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline Flush, 0.9% Injectable Solution</intervention_name>
    <description>The Barre method of intranasal administration will be used to instil 1mL of saline 0.9% in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.</description>
    <arm_group_label>Intranasal normal saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Children aged 7-16 years&#xD;
&#xD;
          2. Migraine headache fulfilling Irma's criteria:&#xD;
&#xD;
               -  Headache lasting 1-72 hours with at least 4 out of 6 of the following features:&#xD;
&#xD;
                    -  Moderate to severe episode of impaired daily activities&#xD;
&#xD;
                    -  Focal localization of headache&#xD;
&#xD;
                    -  Pulsatile description&#xD;
&#xD;
                    -  Nausea or vomiting or abdominal pain&#xD;
&#xD;
                    -  Photophobia, phonophobia, or avoidance of light and noise, or&#xD;
&#xD;
                    -  Symptoms increasing with activity or resolving by rest.&#xD;
&#xD;
             OR:&#xD;
&#xD;
          3. Post-traumatic headache as per ICHD-3 (beta edition) definition with migraine-like&#xD;
             features (see above):&#xD;
&#xD;
             A) Any headache fulfilling criteria C and D&#xD;
&#xD;
             B) Traumatic injury to the head has occurred&#xD;
&#xD;
             C) Headache is reported to have developed within 7 days after one of the following:&#xD;
&#xD;
             i. The injury to the head, ii. Regaining of consciousness following the injury to the&#xD;
             head, iii. Discontinuation of medication(s) that impair ability to sense or report&#xD;
             headache following the injury to the head&#xD;
&#xD;
             D) Headache persists for &gt; 3 months after the injury to the head&#xD;
&#xD;
             E) Not better accounted for by another ICHD-3 diagnosis&#xD;
&#xD;
          4. Verbal report of a pain score of 4 or greater on a 10 point numeric pain score (range&#xD;
             0-10 with increasing severity, i.e. 0 = no pain and 10 = most severe pain) after&#xD;
             receiving first line therapy (non-narcotic analgesia) in either the out-patient or PED&#xD;
             setting&#xD;
&#xD;
          5. Normal vital signs for age&#xD;
&#xD;
          6. Normal neurological exam (no focal deficits or abnormalities)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Families not providing informed consent or assent, where appropriate&#xD;
&#xD;
          2. History of acute trauma or seizure in the preceding 24 hours&#xD;
&#xD;
          3. Clinical suspicion of or known intracranial pathology or underlying central nervous&#xD;
             system disease&#xD;
&#xD;
          4. Headache associated with fever or meningismus&#xD;
&#xD;
          5. Known allergy/sensitivity to lidocaine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Garth Meckler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>BC Children's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6H 3N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 23, 2018</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Garth Meckler</investigator_full_name>
    <investigator_title>Pediatric Emergency Medicine Division Head</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>Post-Traumatic 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>Lidocaine</mesh_term>
    <mesh_term>Pharmaceutical Solutions</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/NCT03806595
org study id: H18-03801
nct id: NCT03806595
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Headaches in children are very common and are a source of significant distress for the
      patient and their family. Migraines are the most common headache disorder in children and are
      associated with episodic pain and other symptoms such as nausea and sensitivity to light and
      sound that can impair a child's ability to participate in daily activities and lead to missed
      school or parental missed work. When home treatment fails to relieve symptoms, children often
      seek care in the emergency department (ED) where a limited number of treatment options exist;
      while largely effective, these rescue treatments currently all require needle insertion of an
      intravenous line, take time to administer, result in prolonged ED stays, and have potential
      unpleasant side effects. In adult patients, a number of studies suggest that lidocaine, a
      local anesthetic administered intranasally, may provide relief of migraine and migraine-like
      headache pain in minutes. This approach has the benefit of working quickly, not requiring a
      needle, and having fewer side effects as the medication acts locally on nerves in the nose.
      Intranasal lidocaine has not yet been studied in children for this purpose. This study will
      compare the use of intranasal lidocaine to placebo. The goal of this pilot study is to
      provide information to inform the sample size calculation for the definitive randomized
      controlled trial that will aim to measure the efficacy of intranasal lidocaine as an
      analgesic option for children age 7 years and older who present to the Pediatric ED with a
      chief complaint of migraine or post traumatic headache with migraine-like features. Secondary
      objectives will be to report on the frequency and severity of rebound headache between the
      two treatment groups, adverse events of the study drug, as well as the impact on healthcare
      utilization measures.The investigators hypothesize that children receiving intranasal
      lidocaine will have faster and more effective pain recovery compared to children receiving
      placebo and will be less likely to require the standard therapy for migraine headache. Given
      very few side effects reported in adult studies and the relatively benign nature of those
      reported, the investigators do not expect any major safety concerns in the study. It is also
      hypothesized that intranasal lidocaine will lead to shorter ED visits, thus reducing use of
      staff and hospital resources and saving money for the healthcare system as a whole.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in migraine pain
time frame: Pain scores will be measured at 30 and 60 minutes post intranasal administration of either the study drug or placebo.
description: The primary outcome measure will be the proportion of subjects with numeric pain scores of < 4 out of 10 on a verbal rating scale (range 0 -10 with increasing severity, i.e. 0 = no pain and 10 = most severe pain).Treatment success is defined as a score of 3 or less at the two time points. This will be recorded for each patient during the study timeframe, until study completion.
measure: Rebound headache
time frame: Pain scores will be recorded at 60 minutes, 24 hours, and within 48-72 hours post intranasal therapy.
description: Proportion of patients with rebound headache (i.e. headache with pain score of greater than or equal to 4 out of 10 on a verbal rating scale; range 0 -10 with increasing severity, i.e. 0 = no pain and 10 = most severe pain). This will be recorded for each patient at the visit of interest during the study timeframe, until study completion.
measure: Emergency department length of stay
time frame: The emergency department length of stay will be ascertained from the medical record within 24 hours of the participant's visit.
description: Number of hours in the Emergency Department from time of registration to time of discharge or admission to hospital for each subject.
measure: Proportion of participants discharged vs. admitted from the emergency department (emergency department disposition)
time frame: Disposition will be ascertained from the medical record within 24 hours of the participant's ED visit.
description: Disposition of the patient from the emergency department for the visit of interest only, i.e. discharge home, hospital admission. This will be recorded for each patient during the study timeframe, until study completion.
measure: Proportion of participants with a return visit to the emergency department within 72 hours of discharge.
time frame: Within 3 days from index visit.
description: Returns to the emergency department for similar complaints of migraine headache or posttraumatic headache with migraine like features.
arm group label: Intranasal lidocaine
arm group type: Experimental
description: 1mL of lidocaine 2% will be instilled in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.
arm group label: Intranasal normal saline
arm group type: Placebo Comparator
description: 1mL of saline 0.9% will be instilled in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.
intervention type: Drug
intervention name: Lidocaine 2% Injectable Solution
description: The Barre method of intranasal administration will be used to instil 1mL of lidocaine 2% in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.
arm group label: Intranasal lidocaine
intervention type: Drug
intervention name: Normal Saline Flush, 0.9% Injectable Solution
description: The Barre method of intranasal administration will be used to instil 1mL of saline 0.9% in either the nostril ipsilateral to the headache or 1ml in each nostril in cases of bilateral headache.
arm group label: Intranasal normal saline
criteria: 
gender: All
minimum age: 7 Years
maximum age: 16 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Garth Meckler, MD
role: Principal Investigator
affiliation: University of British Columbia
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Garth Meckler
investigator title: Pediatric Emergency Medicine Division Head
mesh term: Migraine Disorders
mesh term: Post-Traumatic Headache
mesh term: Headache
mesh term: Lidocaine
mesh term: Pharmaceutical Solutions
sharing ipd: No