<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/NCT01669304</url>
  </required_header>
  <id_info>
    <org_study_id>12-002814</org_study_id>
    <nct_id>NCT01669304</nct_id>
  </id_info>
  <brief_title>Verapamil vs. Sertraline for Vestibular Migraine &amp; Chronic Subjective Dizziness</brief_title>
  <official_title>Pharmacologic Dissection of Vestibular Migraine and Chronic Subjective Dizziness: A Double-Blind Parallel Group Trial Comparing Response to Verapamil Versus Sertraline</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vestibular migraine (VM) and chronic subjective dizziness (CSD) commonly cause vertigo,&#xD;
      unsteadiness and dizziness. Clinical investigators are studying these illnesses to understand&#xD;
      them better. VM and CSD occur together in about 1/3 of patients. That makes it hard to&#xD;
      diagnose them accurately and decide what treatments to use. As a result, doctors and patients&#xD;
      may be confused about these diagnoses. The goal of this study was use two different&#xD;
      medications to tease apart the symptoms of VM and CSD.&#xD;
&#xD;
      Patients who have VM and CSD together were given either verapamil or sertraline for 12 weeks.&#xD;
      These medications are used to treat VM and CSD, though they are not approved for this&#xD;
      purpose. Verapamil is believed to have stronger effects on symptoms of VM. Sertraline is&#xD;
      believed to have stronger effects on symptoms of CSD. By comparing the responses of patients&#xD;
      to these two medications, the researchers hoped to learn more about the key features of VM&#xD;
      and CSD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic dizziness and recurrent vertigo are frequent complaints in primary and specialty&#xD;
      medical care settings. Two common causes of these symptoms are vestibular migraine (VM) and&#xD;
      chronic subjective dizziness (CSD), which may be seen in up to 25% of patients examined in&#xD;
      tertiary neurotology centers. However, VM and CSD are relatively new diagnoses that have not&#xD;
      yet been validated. Furthermore, recent research found that they co-exist 30% of the time&#xD;
      with overlap in several features. From a clinical standpoint, this makes it difficult to&#xD;
      diagnose and treat them well. From a research standpoint, it confounds subject selection for&#xD;
      mechanistic investigations.&#xD;
&#xD;
      The primary goal of this study was to dissect VM and CSD in order to identify the key&#xD;
      features and clarify the diagnostic criteria of each condition. Subjects diagnosed with&#xD;
      coexisting VM-CSD were treated with either verapamil or sertraline. It was hypothesized that&#xD;
      a differential treatment response to these two pharmacologic probes would help to tease apart&#xD;
      the unique clinical features of VM and CSD and identify risk factors that are shared or&#xD;
      separate between the two conditions. It was hoped that the different mechanisms of action of&#xD;
      the two study medications might also shed light on the physiologic underpinnings of VM and&#xD;
      CSD.&#xD;
&#xD;
      This project was a 14-week, prospective, randomized, double-blind, parallel group,&#xD;
      pharmacologic dissection (PD) trial. A 12-week treatment period followed 2 weeks of baseline&#xD;
      observation. Patients charted daily headache and vestibular symptoms. VM and CSD symptoms and&#xD;
      potential confounds such as anxiety and depression were measured at two week intervals. Data&#xD;
      were analyzed for differential and shared treatment effects that align with or oppose current&#xD;
      concepts of VM and CSD.&#xD;
&#xD;
      A PD trial uses response to one or more pharmaceutical probes (drugs) to study physiologic&#xD;
      mechanisms of illness. A PD trial may provide data to separate overlapping manifestations of&#xD;
      comorbid illnesses. This is useful for conditions that lack biomarkers. It also may provide&#xD;
      data to identify characteristics of illnesses (symptoms, signs, cellular processes) that are&#xD;
      associated with specific pharmacologic mechanisms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Diagnostic</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2-week Average Rating of Severity of Headache from the Daily Symptom Diaries</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Daily ratings of headache will be evaluated at 2 week intervals for 12 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2-week Average Rating of Severity of Dizziness/Unsteadiness from the Daily Symptom Diaries</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Daily ratings of dizziness/unsteadiness will be evaluated at 2 week intervals for 12 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2-week Average Rating of Sensitivity to Motion of Self from the Daily Symptom Diaries</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Daily ratings of sensitivity to motion of self will be evaluated at 2 week intervals for 12 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2-week Average Rating of Sensitivity to Motion in the Environment from the Daily Symptom Diaries</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Daily ratings of sensitivity to motion in the environment will be evaluated at 2 week intervals for 12 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2-week Average Rating of Difficulty of Performing Precision Visual Tasks from the Daily Symptom Diaries</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Daily ratings of difficulty of performing precision visual tasks will be evaluated at 2 week intervals for 12 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Number of Acute Attacks Per Two Week Period</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Acute attacks will be assessed every 2 weeks for 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Score of Dizziness Handicap Inventory (DHI)</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Dizziness related handicap will be assessed every 4 weeks for 12 weeks. The Dizziness Handicap Inventory (DHI) consists of 25 questions, with a total possible score ranging from 0 (no dizziness) to 50 (severe dizziness).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Score of Migraine-Specific Quality of Life (MSQ)</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Quality of life related to headache will be assessed at 4 week intervals for 12 weeks. The Migraine-Specific Quality of Life 2.1 (MSQ) consists of 14 items, with a total possible score ranging from 14 (affected none of the time) to 84 (affected all of the time).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mean score for Dizziness on the Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS)</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Dizziness symptoms will be assessed at 2 week intervals for 12 weeks. The Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS) consists of 5 questions, with a total possible score ranging from 0 (no disability) to 72 (extremely disruptive).</description>
  </other_outcome>
  <other_outcome>
    <measure>Mean score for Headache on the Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS)</measure>
    <time_frame>Week 0 to Week 12</time_frame>
    <description>Headache symptoms will be assessed at 2 week intervals for 12 weeks. The Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS) consists of 5 questions, with a total possible score ranging from 0 (no disability) to 72 (extremely disruptive).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Vestibular Migraine</condition>
  <condition>Chronic Subjective Dizziness</condition>
  <arm_group>
    <arm_group_label>Verapamil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Verapamil extended release oral tablets administered in a flexible dose format ranging from 120 mg to 360 mg daily, as determined by severity of headache and dizziness.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sertraline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sertraline oral tablets administered in a flexible dose format ranging from 25 mg to 150 mg daily depending on severity of headache and dizziness.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Verapamil</intervention_name>
    <arm_group_label>Verapamil</arm_group_label>
    <other_name>Calan SR</other_name>
    <other_name>Covera-HS</other_name>
    <other_name>Isoptin SR</other_name>
    <other_name>Verelan PM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline</intervention_name>
    <arm_group_label>Sertraline</arm_group_label>
    <other_name>Zoloft</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Neurotologic diagnoses of both vestibular migraine and chronic subjective dizziness&#xD;
&#xD;
          2. All other co-existing medical or psychiatric conditions are stable, and no greater&#xD;
             than moderate severity&#xD;
&#xD;
          3. Able to complete study assessments in person and by phone&#xD;
&#xD;
          4. Able to travel to Mayo Clinic, Rochester, Minnesota for first and last study visits&#xD;
&#xD;
          5. Willing to avoid pregnancy during study (abstinence or acceptable birth control)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Presence of any other active neurotologic diagnoses&#xD;
&#xD;
          2. Medical or psychiatric conditions that would preclude or confound study drugs&#xD;
&#xD;
          3. Use of medications or supplements that would preclude or confound study drugs&#xD;
&#xD;
          4. Past treatment of headache or dizziness with a full trial of a calcium channel blocker&#xD;
             or selective serotonin reuptake inhibitor&#xD;
&#xD;
          5. Allergy to verapamil or sertraline&#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>Jeffrey Staab, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=101873</url>
    <description>additional research information from Mayo Clinic</description>
  </link>
  <reference>
    <citation>Staab JP, Ruckenstein MJ. Expanding the differential diagnosis of chronic dizziness. Arch Otolaryngol Head Neck Surg. 2007 Feb;133(2):170-6. doi: 10.1001/archotol.133.2.170.</citation>
    <PMID>17309987</PMID>
  </reference>
  <reference>
    <citation>Ruckenstein MJ, Staab JP. Chronic subjective dizziness. Otolaryngol Clin North Am. 2009 Feb;42(1):71-7, ix. doi: 10.1016/j.otc.2008.09.011.</citation>
    <PMID>19134491</PMID>
  </reference>
  <reference>
    <citation>Eggers SD, Staab JP, Neff BA, Goulson AM, Carlson ML, Shepard NT. Investigation of the coherence of definite and probable vestibular migraine as distinct clinical entities. Otol Neurotol. 2011 Sep;32(7):1144-51. doi: 10.1097/MAO.0b013e31822a1c67.</citation>
    <PMID>21799457</PMID>
  </reference>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <last_update_submitted>August 20, 2015</last_update_submitted>
  <last_update_submitted_qc>August 20, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 24, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Jeffrey P. Staab</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>migraine variant</keyword>
  <keyword>chronic dizziness</keyword>
  <keyword>pharmacologic dissection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vertigo</mesh_term>
    <mesh_term>Migraine Disorders</mesh_term>
    <mesh_term>Dizziness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Verapamil</mesh_term>
    <mesh_term>Sertraline</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01669304
org study id: 12-002814
nct id: NCT01669304
lead sponsor: 
has dmc: No
Vestibular migraine (VM) and chronic subjective dizziness (CSD) commonly cause vertigo,
      unsteadiness and dizziness. Clinical investigators are studying these illnesses to understand
      them better. VM and CSD occur together in about 1/3 of patients. That makes it hard to
      diagnose them accurately and decide what treatments to use. As a result, doctors and patients
      may be confused about these diagnoses. The goal of this study was use two different
      medications to tease apart the symptoms of VM and CSD.

      Patients who have VM and CSD together were given either verapamil or sertraline for 12 weeks.
      These medications are used to treat VM and CSD, though they are not approved for this
      purpose. Verapamil is believed to have stronger effects on symptoms of VM. Sertraline is
      believed to have stronger effects on symptoms of CSD. By comparing the responses of patients
      to these two medications, the researchers hoped to learn more about the key features of VM
      and CSD.
Chronic dizziness and recurrent vertigo are frequent complaints in primary and specialty
      medical care settings. Two common causes of these symptoms are vestibular migraine (VM) and
      chronic subjective dizziness (CSD), which may be seen in up to 25% of patients examined in
      tertiary neurotology centers. However, VM and CSD are relatively new diagnoses that have not
      yet been validated. Furthermore, recent research found that they co-exist 30% of the time
      with overlap in several features. From a clinical standpoint, this makes it difficult to
      diagnose and treat them well. From a research standpoint, it confounds subject selection for
      mechanistic investigations.

      The primary goal of this study was to dissect VM and CSD in order to identify the key
      features and clarify the diagnostic criteria of each condition. Subjects diagnosed with
      coexisting VM-CSD were treated with either verapamil or sertraline. It was hypothesized that
      a differential treatment response to these two pharmacologic probes would help to tease apart
      the unique clinical features of VM and CSD and identify risk factors that are shared or
      separate between the two conditions. It was hoped that the different mechanisms of action of
      the two study medications might also shed light on the physiologic underpinnings of VM and
      CSD.

      This project was a 14-week, prospective, randomized, double-blind, parallel group,
      pharmacologic dissection (PD) trial. A 12-week treatment period followed 2 weeks of baseline
      observation. Patients charted daily headache and vestibular symptoms. VM and CSD symptoms and
      potential confounds such as anxiety and depression were measured at two week intervals. Data
      were analyzed for differential and shared treatment effects that align with or oppose current
      concepts of VM and CSD.

      A PD trial uses response to one or more pharmaceutical probes (drugs) to study physiologic
      mechanisms of illness. A PD trial may provide data to separate overlapping manifestations of
      comorbid illnesses. This is useful for conditions that lack biomarkers. It also may provide
      data to identify characteristics of illnesses (symptoms, signs, cellular processes) that are
      associated with specific pharmacologic mechanisms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 2-week Average Rating of Severity of Headache from the Daily Symptom Diaries
time frame: Week 0 to Week 12
description: Daily ratings of headache will be evaluated at 2 week intervals for 12 weeks.
measure: 2-week Average Rating of Severity of Dizziness/Unsteadiness from the Daily Symptom Diaries
time frame: Week 0 to Week 12
description: Daily ratings of dizziness/unsteadiness will be evaluated at 2 week intervals for 12 weeks.
measure: 2-week Average Rating of Sensitivity to Motion of Self from the Daily Symptom Diaries
time frame: Week 0 to Week 12
description: Daily ratings of sensitivity to motion of self will be evaluated at 2 week intervals for 12 weeks.
measure: 2-week Average Rating of Sensitivity to Motion in the Environment from the Daily Symptom Diaries
time frame: Week 0 to Week 12
description: Daily ratings of sensitivity to motion in the environment will be evaluated at 2 week intervals for 12 weeks.
measure: 2-week Average Rating of Difficulty of Performing Precision Visual Tasks from the Daily Symptom Diaries
time frame: Week 0 to Week 12
description: Daily ratings of difficulty of performing precision visual tasks will be evaluated at 2 week intervals for 12 weeks.
measure: Mean Number of Acute Attacks Per Two Week Period
time frame: Week 0 to Week 12
description: Acute attacks will be assessed every 2 weeks for 12 weeks.
measure: Mean Score of Dizziness Handicap Inventory (DHI)
time frame: Week 0 to Week 12
description: Dizziness related handicap will be assessed every 4 weeks for 12 weeks. The Dizziness Handicap Inventory (DHI) consists of 25 questions, with a total possible score ranging from 0 (no dizziness) to 50 (severe dizziness).
measure: Mean Score of Migraine-Specific Quality of Life (MSQ)
time frame: Week 0 to Week 12
description: Quality of life related to headache will be assessed at 4 week intervals for 12 weeks. The Migraine-Specific Quality of Life 2.1 (MSQ) consists of 14 items, with a total possible score ranging from 14 (affected none of the time) to 84 (affected all of the time).
measure: Mean score for Dizziness on the Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS)
time frame: Week 0 to Week 12
description: Dizziness symptoms will be assessed at 2 week intervals for 12 weeks. The Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS) consists of 5 questions, with a total possible score ranging from 0 (no disability) to 72 (extremely disruptive).
measure: Mean score for Headache on the Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS)
time frame: Week 0 to Week 12
description: Headache symptoms will be assessed at 2 week intervals for 12 weeks. The Sheehan Disability Scale/Migraine Disability Assessment Scale (SDS-MIDAS) consists of 5 questions, with a total possible score ranging from 0 (no disability) to 72 (extremely disruptive).
arm group label: Verapamil
arm group type: Experimental
description: Verapamil extended release oral tablets administered in a flexible dose format ranging from 120 mg to 360 mg daily, as determined by severity of headache and dizziness.
arm group label: Sertraline
arm group type: Experimental
description: Sertraline oral tablets administered in a flexible dose format ranging from 25 mg to 150 mg daily depending on severity of headache and dizziness.
intervention type: Drug
intervention name: Verapamil
arm group label: Verapamil
other name: Calan SR
other name: Covera-HS
other name: Isoptin SR
other name: Verelan PM
intervention type: Drug
intervention name: Sertraline
arm group label: Sertraline
other name: Zoloft
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey Staab, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=101873
description: additional research information from Mayo Clinic
citation: Staab JP, Ruckenstein MJ. Expanding the differential diagnosis of chronic dizziness. Arch Otolaryngol Head Neck Surg. 2007 Feb;133(2):170-6. doi: 10.1001/archotol.133.2.170.
PMID: 17309987
citation: Ruckenstein MJ, Staab JP. Chronic subjective dizziness. Otolaryngol Clin North Am. 2009 Feb;42(1):71-7, ix. doi: 10.1016/j.otc.2008.09.011.
PMID: 19134491
citation: Eggers SD, Staab JP, Neff BA, Goulson AM, Carlson ML, Shepard NT. Investigation of the coherence of definite and probable vestibular migraine as distinct clinical entities. Otol Neurotol. 2011 Sep;32(7):1144-51. doi: 10.1097/MAO.0b013e31822a1c67.
PMID: 21799457
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Jeffrey P. Staab
investigator title: Associate Professor
mesh term: Vertigo
mesh term: Migraine Disorders
mesh term: Dizziness
mesh term: Verapamil
mesh term: Sertraline