<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/NCT01687088</url>
  </required_header>
  <id_info>
    <org_study_id>MJM/Olfactory/002</org_study_id>
    <nct_id>NCT01687088</nct_id>
  </id_info>
  <brief_title>Smell Sensitivity in Chronic Migraine: A Case-Control Study</brief_title>
  <official_title>Olfactory Acuity in Chronic Migraine: A Case-Control Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Thomas Jefferson University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Olfactory impairment is a common symptom of neurologic disorders and may be related to&#xD;
      dopaminergic dysfunction. Studies show that patients with migraine show increased sensitivity&#xD;
      to light and sound. In our previous study in episodic migraineurs, olfaction was similar to&#xD;
      age and sex-matched controls outside of attacks, but lower during acute attacks.&#xD;
&#xD;
      The hypothesis is that olfactory function in chronic migraine (CM) will have mild impairment&#xD;
      of olfaction at baseline but a more significant impairment during migraine or headache&#xD;
      exacerbations.&#xD;
&#xD;
      The investigators have two objectives:&#xD;
&#xD;
        -  To determine baseline olfactory acuity in subjects with CM and compare them to age and&#xD;
           sex-matched controls&#xD;
&#xD;
        -  To determine how olfaction changes during acute exacerbations of migraine in those with&#xD;
           CM&#xD;
&#xD;
      To execute this study, the investigators will interview subjects and controls to ensure that&#xD;
      they meet inclusion and exclusion criteria. After obtaining informed consent, subjects and&#xD;
      controls will complete a questionnaire survey regarding their history or lack of history of&#xD;
      headaches, smell sensitivity, osmophobia and current medication use and answer questions&#xD;
      about attack frequency, location of headache, duration of disease, use of medication for&#xD;
      pain, and disability. Both migraineurs and controls will take the University of Pennsylvania&#xD;
      Smell Identification Test (UPSIT) in the office.&#xD;
&#xD;
      After the first visit, migraineurs and controls will self-administer the UPSIT at home. They&#xD;
      will be required to return the second test to the Jefferson Headache Center.&#xD;
&#xD;
      The investigators will use analysis of variance (ANOVA) to determine variance in UPSIT scores&#xD;
      between subjects and controls. To achieve a 90% power that the study will detect a&#xD;
      statistically significant difference between the mean UPSIT scores at a two-sided 5 percent&#xD;
      significance level, our sample size for both subjects and controls is 50.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will interview subjects and controls to ensure that they meet inclusion&#xD;
      criteria and do not meet exclusion criteria. After obtaining informed consent, subjects and&#xD;
      controls will complete a questionnaire survey with the interviewer regarding their history of&#xD;
      headaches, smell sensitivity, osmophobia and current medication use. Subjects will also&#xD;
      answer questions about attack frequency, location of headache, duration of disease, use of&#xD;
      medication for pain, and disability.&#xD;
&#xD;
      After completing the questionnaire survey, migraineurs and controls will take the University&#xD;
      of Pennsylvania Smell Identification Test (UPSIT) in the office. During this visit we will&#xD;
      demonstrate and give instructions on how to perform UPSIT at home.&#xD;
&#xD;
      After the first visit, migraineurs will self-administer the UPSIT during a migraine attack&#xD;
      day at home. They will be required to mail or drop off the second test at the Jefferson&#xD;
      Headache Center.&#xD;
&#xD;
      Age and sex matched controls will take the first UPSIT in the office. They will take second&#xD;
      UPSIT 2 weeks later at home and call the Headache Center to notify the staff that they have&#xD;
      completed the second UPSIT. They will be asked to mail or drop off the test at the Jefferson&#xD;
      Headache Center.&#xD;
&#xD;
      The UPSIT is a standardized, validated test for olfaction. There are a total of 40 odorants,&#xD;
      with four booklets each containing ten odorants. The stimuli are embedded in &quot;scratch and&#xD;
      sniff&quot; microcapsules at the bottom of each page. Subjects must choose one answer among four&#xD;
      possible answers for each odorant - a forced choice test. The validity and reliability of the&#xD;
      UPSIT, as well as the basis for using these particular odorants, has been demonstrated in&#xD;
      multiple studies. The tests kits will be supplied by Dr. Richard Doty at University of&#xD;
      Pennsylvania.&#xD;
&#xD;
      The investigators will use analysis of variance (ANOVA) to determine variance in UPSIT scores&#xD;
      between subjects and controls. We will also use ANOVA to examine differences based on subject&#xD;
      characteristics, including attack frequency, duration of illness, osmophobia during attacks,&#xD;
      and if odors trigger headaches. The investigators will also use Chi-square and the Wilcoxon&#xD;
      rank sum test to determine categorical outcomes such as gender and statistical significance&#xD;
      between groups.&#xD;
&#xD;
      To achieve a 90% power that the study will detect a statistically significant difference&#xD;
      between the mean UPSIT scores at a two-sided 5 percent significance level, our sample size&#xD;
      for both subjects and controls is 50. This is based on the assumption that the standard&#xD;
      deviation of the response variable is 3 units. The investigator's assumptions about effect&#xD;
      size are based on previous studies using the UPSIT to detect differences in subjects and&#xD;
      controls in other neurologic disorders, such as schizophrenia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2011</start_date>
  <completion_date type="Actual">March 2012</completion_date>
  <primary_completion_date type="Actual">March 2012</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of UPSIT Scores Between Subjects and Controls at Two Time Points</measure>
    <time_frame>Chronic migraineurs up to 12 months. Controls up to 2 weeks.</time_frame>
    <description>Migraineurs and controls will take the University of Pennsylvania Smell Identification Test (UPSIT) in the office. The UPSIT test is a series of 40 questions and the score is the number of questions answered correctly. Each question is multiple choice and must be answered. The number of correct answers regarding the smells being experienced is the subjects score. The higher the score the better the sense of smell. This allows groups to be compared. In this study after the first visit, migraineurs will be given the UPSIT test without a headache and then they will self-administer the UPSIT during a migraine attack day at home.&#xD;
Age and sex matched controls will also take the first UPSIT in the office. They will take second UPSIT 2 weeks later at home.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Chronic Migraine</condition>
  <condition>Olfactory Acuity</condition>
  <arm_group>
    <arm_group_label>chronic migraineurs</arm_group_label>
    <description>At least 8 migraine days per week and headache at least 15 days per month.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>controls</arm_group_label>
    <description>No significant headache or disability as defined by migraine disability scale.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Male and female subjects, over age 18 years who meet criteria for diagnosis of chronic&#xD;
        migraine Controls will be age and sex-matched and will have no history of migraine&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects over the age of 18 with Chronic Migraine (&gt;15 headache&#xD;
             days/month, at least 8 days meet criteria for migraine)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with sinus/nasal disease&#xD;
&#xD;
          -  Subjects with a history of head trauma or degenerative disease&#xD;
&#xD;
          -  Subjects who are decisionally impaired.&#xD;
&#xD;
          -  Controls will be age and sex-matched with no history of migraine. They cannot have any&#xD;
             disability from headache as determined by the MIDAS (Migraine Disability Assessment)&#xD;
             questionnaire. Only controls with a MIDAS score of &quot;0&quot; (no disability) will be allowed&#xD;
             in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael McNamara, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Thomas Jefferson University</affiliation>
  </overall_official>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <results_first_submitted>July 14, 2014</results_first_submitted>
  <results_first_submitted_qc>October 21, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 24, 2014</results_first_posted>
  <last_update_submitted>October 21, 2014</last_update_submitted>
  <last_update_submitted_qc>October 21, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 24, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Chronic Migraineurs</title>
          <description>At least 8 migraine days per week and headache at least 15 days per month.</description>
        </group>
        <group group_id="P2">
          <title>Controls</title>
          <description>No significant headache or disability as defined by migraine disability scale.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Chronic Migraineurs</title>
          <description>At least 8 migraine days per week and headache at least 15 days per month.</description>
        </group>
        <group group_id="B2">
          <title>Controls</title>
          <description>No significant headache or disability as defined by migraine disability scale.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="50"/>
            <count group_id="B2" value="50"/>
            <count group_id="B3" value="100"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="100"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Comparison of UPSIT Scores Between Subjects and Controls at Two Time Points</title>
        <description>Migraineurs and controls will take the University of Pennsylvania Smell Identification Test (UPSIT) in the office. The UPSIT test is a series of 40 questions and the score is the number of questions answered correctly. Each question is multiple choice and must be answered. The number of correct answers regarding the smells being experienced is the subjects score. The higher the score the better the sense of smell. This allows groups to be compared. In this study after the first visit, migraineurs will be given the UPSIT test without a headache and then they will self-administer the UPSIT during a migraine attack day at home.&#xD;
Age and sex matched controls will also take the first UPSIT in the office. They will take second UPSIT 2 weeks later at home.</description>
        <time_frame>Chronic migraineurs up to 12 months. Controls up to 2 weeks.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Chronic Migraineurs</title>
            <description>At least 8 migraine days per week and headache at least 15 days per month.</description>
          </group>
          <group group_id="O2">
            <title>Controls</title>
            <description>No significant headache or disability as defined by migraine disability scale.</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of UPSIT Scores Between Subjects and Controls at Two Time Points</title>
          <description>Migraineurs and controls will take the University of Pennsylvania Smell Identification Test (UPSIT) in the office. The UPSIT test is a series of 40 questions and the score is the number of questions answered correctly. Each question is multiple choice and must be answered. The number of correct answers regarding the smells being experienced is the subjects score. The higher the score the better the sense of smell. This allows groups to be compared. In this study after the first visit, migraineurs will be given the UPSIT test without a headache and then they will self-administer the UPSIT during a migraine attack day at home.&#xD;
Age and sex matched controls will also take the first UPSIT in the office. They will take second UPSIT 2 weeks later at home.</description>
          <units>UPSIT Score</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>First UPSIT Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.5" spread="0.4"/>
                    <measurement group_id="O2" value="35.9" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Second UPSIT Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.7" spread="0.4"/>
                    <measurement group_id="O2" value="36.1" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Chronic Migraineurs</title>
          <description>At least 8 migraine days per week and headache at least 15 days per month.</description>
        </group>
        <group group_id="E2">
          <title>Controls</title>
          <description>No significant headache or disability as defined by migraine disability scale.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael J. Marmura, MD</name_or_title>
      <organization>Thomas Jefferson University</organization>
      <phone>215-955-2243</phone>
      <email>michael.marmura@jefferson.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01687088
org study id: MJM/Olfactory/002
nct id: NCT01687088
lead sponsor: 
collaborator: 
has dmc: No
Olfactory impairment is a common symptom of neurologic disorders and may be related to
      dopaminergic dysfunction. Studies show that patients with migraine show increased sensitivity
      to light and sound. In our previous study in episodic migraineurs, olfaction was similar to
      age and sex-matched controls outside of attacks, but lower during acute attacks.

      The hypothesis is that olfactory function in chronic migraine (CM) will have mild impairment
      of olfaction at baseline but a more significant impairment during migraine or headache
      exacerbations.

      The investigators have two objectives:

        -  To determine baseline olfactory acuity in subjects with CM and compare them to age and
           sex-matched controls

        -  To determine how olfaction changes during acute exacerbations of migraine in those with
           CM

      To execute this study, the investigators will interview subjects and controls to ensure that
      they meet inclusion and exclusion criteria. After obtaining informed consent, subjects and
      controls will complete a questionnaire survey regarding their history or lack of history of
      headaches, smell sensitivity, osmophobia and current medication use and answer questions
      about attack frequency, location of headache, duration of disease, use of medication for
      pain, and disability. Both migraineurs and controls will take the University of Pennsylvania
      Smell Identification Test (UPSIT) in the office.

      After the first visit, migraineurs and controls will self-administer the UPSIT at home. They
      will be required to return the second test to the Jefferson Headache Center.

      The investigators will use analysis of variance (ANOVA) to determine variance in UPSIT scores
      between subjects and controls. To achieve a 90% power that the study will detect a
      statistically significant difference between the mean UPSIT scores at a two-sided 5 percent
      significance level, our sample size for both subjects and controls is 50.
The investigators will interview subjects and controls to ensure that they meet inclusion
      criteria and do not meet exclusion criteria. After obtaining informed consent, subjects and
      controls will complete a questionnaire survey with the interviewer regarding their history of
      headaches, smell sensitivity, osmophobia and current medication use. Subjects will also
      answer questions about attack frequency, location of headache, duration of disease, use of
      medication for pain, and disability.

      After completing the questionnaire survey, migraineurs and controls will take the University
      of Pennsylvania Smell Identification Test (UPSIT) in the office. During this visit we will
      demonstrate and give instructions on how to perform UPSIT at home.

      After the first visit, migraineurs will self-administer the UPSIT during a migraine attack
      day at home. They will be required to mail or drop off the second test at the Jefferson
      Headache Center.

      Age and sex matched controls will take the first UPSIT in the office. They will take second
      UPSIT 2 weeks later at home and call the Headache Center to notify the staff that they have
      completed the second UPSIT. They will be asked to mail or drop off the test at the Jefferson
      Headache Center.

      The UPSIT is a standardized, validated test for olfaction. There are a total of 40 odorants,
      with four booklets each containing ten odorants. The stimuli are embedded in "scratch and
      sniff" microcapsules at the bottom of each page. Subjects must choose one answer among four
      possible answers for each odorant - a forced choice test. The validity and reliability of the
      UPSIT, as well as the basis for using these particular odorants, has been demonstrated in
      multiple studies. The tests kits will be supplied by Dr. Richard Doty at University of
      Pennsylvania.

      The investigators will use analysis of variance (ANOVA) to determine variance in UPSIT scores
      between subjects and controls. We will also use ANOVA to examine differences based on subject
      characteristics, including attack frequency, duration of illness, osmophobia during attacks,
      and if odors trigger headaches. The investigators will also use Chi-square and the Wilcoxon
      rank sum test to determine categorical outcomes such as gender and statistical significance
      between groups.

      To achieve a 90% power that the study will detect a statistically significant difference
      between the mean UPSIT scores at a two-sided 5 percent significance level, our sample size
      for both subjects and controls is 50. This is based on the assumption that the standard
      deviation of the response variable is 3 units. The investigator's assumptions about effect
      size are based on previous studies using the UPSIT to detect differences in subjects and
      controls in other neurologic disorders, such as schizophrenia.
observational model: Case-Control
time perspective: Prospective
measure: Comparison of UPSIT Scores Between Subjects and Controls at Two Time Points
time frame: Chronic migraineurs up to 12 months. Controls up to 2 weeks.
description: Migraineurs and controls will take the University of Pennsylvania Smell Identification Test (UPSIT) in the office. The UPSIT test is a series of 40 questions and the score is the number of questions answered correctly. Each question is multiple choice and must be answered. The number of correct answers regarding the smells being experienced is the subjects score. The higher the score the better the sense of smell. This allows groups to be compared. In this study after the first visit, migraineurs will be given the UPSIT test without a headache and then they will self-administer the UPSIT during a migraine attack day at home.
Age and sex matched controls will also take the first UPSIT in the office. They will take second UPSIT 2 weeks later at home.
arm group label: chronic migraineurs
description: At least 8 migraine days per week and headache at least 15 days per month.
arm group label: controls
description: No significant headache or disability as defined by migraine disability scale.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael McNamara, MD
role: Principal Investigator
affiliation: Thomas Jefferson University
responsible party type: Sponsor
mesh term: Migraine Disorders
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 