<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/NCT01709708</url>
  </required_header>
  <id_info>
    <org_study_id>12-004TI</org_study_id>
    <nct_id>NCT01709708</nct_id>
  </id_info>
  <brief_title>Use of the Tx360 Nasal Applicator in the Treatment of Chronic Migraine</brief_title>
  <acronym>Tx360</acronym>
  <official_title>Use of the Tx360 Nasal Applicator for Transnasal Sphenopalatine Ganglion Block in the Treatment of Chronic Migraine: A Double-blind Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tian Medical Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinvest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tian Medical Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Migraine imposes a substantial burden on patients in terms of diminished daily functioning,&#xD;
      quality of life, and financial loss. Pain severity and duration correlates with reduced&#xD;
      measures of daily functioning, and overall health status. The sphenopalatine ganglion (SPG)&#xD;
      has been implicated in a variety of cephalalgias. This has been well represented in the&#xD;
      literature dating back over a century. Access to this structure can be gained via a small&#xD;
      area of mucosa just posterior and superior to the tail of the middle turbinate on the lateral&#xD;
      nasal wall. At this aspect, there is no bony boundary to the SPG. Blocking the SPG using&#xD;
      local anesthetics relieves pain. Unfortunately, many current interventions are cumbersome,&#xD;
      invasive, and expensive. The purpose of this study is to evaluate the efficacy of the Tx360™,&#xD;
      a new nasal applicator device, in the treatment of head and face pain and to examine the&#xD;
      economic implications. The Tx360™ is a single use device designed to deliver a topical local&#xD;
      anesthetic to the specific area of mucosa associated with the SPG. A total of 42 study&#xD;
      participants will be accepted into this double-blind placebo-controlled study. 28 will&#xD;
      receive SPG blocks using a 0.3 mL of a 0.5% solution of Marcaine delivered by the Tx360™&#xD;
      while 14 will receive a placebo of saline substituted for the Marcaine. Both patient sets&#xD;
      will also be given a piece of lemon hard candy as a taste distractor. Participants must have&#xD;
      a chronic migraine history with over 15 symptomatic days per month over the past three&#xD;
      months. The treatment plan consists of six weeks of treatment, two times per week. Short and&#xD;
      longer term assessments will be retrieved and analyzed as detailed in the Study Design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      42 study participants will be included in this double-blind placebo-controlled study.&#xD;
      Following enrollment of 42 subjects and completion of the 6-week Treatment Period by all&#xD;
      active subjects, an analysis of the treatment effect will be performed for a reassessment of&#xD;
      sample size and, if deemed appropriate, the study will continue with enrollment of additional&#xD;
      subjects to ensure a more statistically robust interpretation of the data. The results of the&#xD;
      statistical analysis will be blinded from Investigators and coordinators. The procedure will&#xD;
      be delivered to all subjects who agree to participate, meet inclusion criteria, and sign&#xD;
      informed consent.&#xD;
&#xD;
      At Visit 1 following Informed Consent, a physical exam and vital signs will be completed. A&#xD;
      medical, headache, and medication history (to include age, sex, height and weight, and&#xD;
      duration and location of headache pain, as well as history of ER visits) will be collected on&#xD;
      all subjects. Eligible subjects will be provided with a Baseline Headache Diary and&#xD;
      instructed to treat migraines for the following month in their usual manner with their usual&#xD;
      treatment. The daily Diary will document headache, acute treatment and response, and migraine&#xD;
      associated symptoms (nausea, vomiting, light sensitivity, or sound sensitivity) to establish&#xD;
      a Baseline number of headache days and severity. Visit 2 will be scheduled for 1 month&#xD;
      following Visit 1. Following Visit 1, Visits 2-13 (treatment visits) will be scheduled to&#xD;
      occur twice weekly (during the regular Monday - Friday work week) at least 2 days apart.&#xD;
      Treatments should not occur on consecutive days.&#xD;
&#xD;
      At Visit 2, the Baseline Headache Diary will be reviewed and those subjects continuing to&#xD;
      meet eligibility will be dispensed a 6-week Treatment Period Diary and complete Before&#xD;
      Procedure questions to include the Pain Intensity Numeric Rating Scale (NRS), the Modified&#xD;
      Pain Characteristic Questionnaire, and a baseline Headache Impact Test-6 (HIT-6), have vital&#xD;
      signs completed, and the medical, headache, and medication history updated. Subjects will be&#xD;
      randomized 2:1 to Group A or Group B. Group A will receive treatment with 0.3 mL of 0.5%&#xD;
      Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the SPG.&#xD;
      Group B will receive saline substituted for Marcaine delivered bilaterally with the Tx360TM&#xD;
      device to the mucosa associated with the SPG.&#xD;
&#xD;
      To maintain the blinding of the treatment groups, neither the Investigator nor research&#xD;
      personnel who are involved in evaluating the subject should prepare the study medication. An&#xD;
      independent research staff person with no involvement in the study conduct will place study&#xD;
      medication (either Marcaine for a subject randomized to Group A or Placebo/saline for a&#xD;
      subject randomized to Group B) in a 1cc Luer Lok tip syringe and assemble the syringe and&#xD;
      Tx360TM catheter as instructed in training. A label with the subject Drug Number will be&#xD;
      placed on the device at that time. The research staff person administering the study&#xD;
      medication will verify that the Drug Number assignment is correct.&#xD;
&#xD;
      Both Groups will be given a piece of lemon hard candy as a taste distractor.&#xD;
&#xD;
      At each treatment visit (Visits 2-13), in addition to Before Procedure questions, subjects&#xD;
      will complete 15-minute and 30-minute After Procedure questionnaires to include the NRS and,&#xD;
      at 30 minutes, the Patient's Global Impression of Change (PGIC). Subjects will take home a&#xD;
      questionnaire to include the NRS, PGIC, satisfaction question, and the Modified Pain&#xD;
      Characteristic Questionnaire to be completed at 24 hours following treatment and be&#xD;
      instructed to return the 24-hour After Procedure questionnaire to the clinic at the next&#xD;
      visit.&#xD;
&#xD;
      At Visits 2-15 vital signs will be completed, medications will be updated, and Non-Serious&#xD;
      Adverse Events will be collected after the first treatment. Serious Adverse Events will be&#xD;
      collected once the informed consent has been signed and throughout the study.&#xD;
&#xD;
      At Visits 5, 8, and 11, the Treatment Period Headache Diary will be collected, reviewed, and&#xD;
      re-dispensed.&#xD;
&#xD;
      At Visit 13, the 1-Month Post-Treatment Period Diary will be dispensed.&#xD;
&#xD;
      The subject will return to the clinic at Visit 14 between 24 and 96 hours following the final&#xD;
      treatment at Visit 13 to return the 24-hour After Procedure Questionnaire and complete the&#xD;
      1-Month Treatment Period HIT-6. The Treatment Period Diary will be collected.&#xD;
&#xD;
      At Visit 15, 1 month following the final treatment, each subject will return to the clinic&#xD;
      and complete a 1-Month Follow Up HIT-6 and the 1-Month Follow Up Questionnaire. The 1-Month&#xD;
      Post-Treatment Period Diary will be collected.&#xD;
&#xD;
      At 6 months following the final treatment, each subject will be phoned to complete the&#xD;
      6-Month Follow Up Questionnaire to include the NRS, PGIC, satisfaction question, the Modified&#xD;
      Pain Characteristic Questionnaire, and a 6-Month Follow Up HIT-6.&#xD;
&#xD;
      Treatment Medication Subjects randomized to Group A will be administered 0.3 mL of 0.5%&#xD;
      Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the SPG.&#xD;
      Twelve treatments will be administered over a period of 6 weeks.&#xD;
&#xD;
      Subjects randomized to Group B will be administered saline substituted for Marcaine delivered&#xD;
      bilaterally with the Tx360TM device to the mucosa associated with the SPG for treatment of&#xD;
      chronic migraine. Twelve treatments will be administered over a period of 6 weeks.&#xD;
&#xD;
      Rescue Medication Subjects will be allowed to rescue with medication mutually agreed upon by&#xD;
      subject and Investigator at the time of screening.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">February 2014</completion_date>
  <primary_completion_date type="Actual">February 2014</primary_completion_date>
  <phase>Phase 4</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Numeric Rating Scale (NRS)</measure>
    <time_frame>6 Weeks</time_frame>
    <description>Compare Numeric Rating Scale (NRS) scores Before Procedure,15-Minute Post Treatment, 30-Minutes Post Treatment, 24-Hour Post Treatment for all 12 treatments (Marcaine vs. Saline). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain. For each individual time point, all 12 treatments were averaged for that time point and a single value was used for comparison between the two groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Numeric Rating Scale (NRS)</measure>
    <time_frame>15 Minutes Post Treatment, 30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks</time_frame>
    <description>Compare percentage change in Numeric Rating Scale (NRS) score from Before Procedure to 15-Minutes, Before Procedure to 30-Minutes, Before Procedure to 24-Hours After Procedure for all 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's Global Impression of Change (PGIC)</measure>
    <time_frame>30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks</time_frame>
    <description>Compare 24-Hour After Procedure Patient's Global Impression of Change (PGIC) score for 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). PGIC is a likert scale ranging from 1 to 7 with 1 being very much improved and 7 being very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Pain Characteristic Questionnaire</measure>
    <time_frame>Before Treatment, 24 Hours After Treatment, 1 Month Post Treatment, and 6 Months Post Treatment</time_frame>
    <description>Compare Modified Pain Characteristic Questionnaire scores Before Procedure vs. 24-Hour After Procedure, Before Procedure vs. 1-Month Follow Up, and Before Procedure vs. 6-Month Follow Up (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). The modified pain characteristic questionnaire is a series of 11 questions on a likert scale ranging from 0 to 10 with 0 being no pain or does not interfere and 10 being worst pain or completely interferes. Percentage questions range from 0 to 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Migraine Headache Days</measure>
    <time_frame>12 Weeks</time_frame>
    <description>Compare change in the number of migraine headache days per month reported in Baseline Period Diary vs. Treatment Period Diary vs. Post-Treatment Period Diary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Medications Usage</measure>
    <time_frame>10 Weeks</time_frame>
    <description>Number of acute medications used during Treatment period (6 weeks) and Follow-Up (4 weeks) (Group A vs. Group B).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>34 weeks</time_frame>
    <description>Number of adverse events over the entire length of study (Group A vs. Group B).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Headache Impact Test (HIT-6)</measure>
    <time_frame>10 Weeks</time_frame>
    <description>Total Headache Impact Test (HIT-6) scores Pre-Treatment at Visit 2 vs. Post-Treatment (following final treatment), and at 1-Month Post-Treatment (Group A vs. Group B). HIT-6 is a series of 6 likert scale questions ranging from 1 to 5 with 1 being never and 5 being always. The HIT-6 answer options are weighted as follows: Never (1) = 6 points each, Rarely (2) = 9 points each, Sometimes (3) = 10 points each, Very often (4) = 11 points each, Always (5) = 13 points each. The total score for the HIT-6 ranges from 36 (subject answers all 6 questions as &quot;Never&quot;) to 78 subject answers all 6 questions as &quot;Always&quot;), with higher total scores indicating more impact than lower scores, i.e., headaches cause greater impact on the subject's life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Satisfaction</measure>
    <time_frame>10 Weeks</time_frame>
    <description>Satisfaction scores Visit 2 vs. following treatment (Treatment 12) and at 1-Month Post-Treatment (Group A vs. Group B). Satisfaction scores are a likert scale ranging from 1 to 5 with 1 being complete dissatisfaction and 5 being complete satisfaction.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Chronic Migraine</condition>
  <arm_group>
    <arm_group_label>Marcaine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Marcaine</intervention_name>
    <description>Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
    <arm_group_label>Marcaine</arm_group_label>
    <other_name>Bupivicane (generic)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Saline</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Is male or female, in otherwise good health, 18 to 80 years of age.&#xD;
&#xD;
          2. Has history of chronic migraine (with or without aura) according to the criteria&#xD;
             proposed by the Headache Classification Committee of the International Headache&#xD;
             Society for at least 3 months prior to enrollment.&#xD;
&#xD;
          3. Has onset of migraine before age 50.&#xD;
&#xD;
          4. Is able to differentiate migraine from any other headache they may experience (e.g.,&#xD;
             tension-type headache).&#xD;
&#xD;
          5. Is not currently taking a migraine preventive or has been taking preventive for at&#xD;
             least 30 days prior to screening and agrees to not start, stop, or change medication&#xD;
             and/or dosage during the study period.&#xD;
&#xD;
          6. If female of childbearing potential, agrees to use, for the duration of the study, a&#xD;
             medically acceptable form of contraception as determined by the Investigator.&#xD;
&#xD;
               1. Complete abstinence from intercourse from 2 weeks prior to administration of&#xD;
                  study drug throughout the study, and for a time interval after completion or&#xD;
                  premature discontinuation from the study to account for elimination of the study&#xD;
                  drug; or,&#xD;
&#xD;
               2. Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of&#xD;
                  pregnancy); or,&#xD;
&#xD;
               3. Sterilization of male partner; or,&#xD;
&#xD;
               4. Intrauterine device with published data showing lowest expected failure rate is&#xD;
                  less than 1% per year; or,&#xD;
&#xD;
               5. Double barrier method (i.e., 2 physical barriers OR 1 physical barrier plus&#xD;
                  spermicide) for a least 1 month prior to Visit 1 and throughout study; or,&#xD;
&#xD;
               6. Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout&#xD;
                  study.&#xD;
&#xD;
          7. Has pain presentation in frontal, temporal, ophthalmic, maxillary, mandibular, facial,&#xD;
             or intraoral location.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Is male or female, in otherwise good health, 18 to 80 years of age.&#xD;
&#xD;
          2. Has history of chronic migraine (with or without aura) according to the criteria&#xD;
             proposed by the Headache Classification Committee of the International Headache&#xD;
             Society for at least 3 months prior to enrollment.&#xD;
&#xD;
          3. Has onset of migraine before age 50.&#xD;
&#xD;
          4. Is able to differentiate migraine from any other headache they may experience (e.g.,&#xD;
             tension-type headache).&#xD;
&#xD;
          5. Is not currently taking a migraine preventive or has been taking preventive for at&#xD;
             least 30 days prior to screening and agrees to not start, stop, or change medication&#xD;
             and/or dosage during the study period.&#xD;
&#xD;
          6. If female of childbearing potential, agrees to use, for the duration of the study, a&#xD;
             medically acceptable form of contraception as determined by the Investigator.&#xD;
&#xD;
               1. Complete abstinence from intercourse from 2 weeks prior to administration of&#xD;
                  study drug throughout the study, and for a time interval after completion or&#xD;
                  premature discontinuation from the study to account for elimination of the study&#xD;
                  drug; or,&#xD;
&#xD;
               2. Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of&#xD;
                  pregnancy); or,&#xD;
&#xD;
               3. Sterilization of male partner; or,&#xD;
&#xD;
               4. Intrauterine device with published data showing lowest expected failure rate is&#xD;
                  less than 1% per year; or,&#xD;
&#xD;
               5. Double barrier method (i.e., 2 physical barriers OR 1 physical barrier plus&#xD;
                  spermicide) for a least 1 month prior to Visit 1 and throughout study; or,&#xD;
&#xD;
               6. Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout&#xD;
                  study.&#xD;
&#xD;
          7. Has pain presentation in frontal, temporal, ophthalmic, maxillary, mandibular, facial,&#xD;
             or intraoral location.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tian Xia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tian Medical Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Michigan Head Pain &amp; Neurological Institute</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinvest/A Division of Banyan Group, Inc.</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.tianmedical.com</url>
    <description>Instructions for use and device training</description>
  </link>
  <reference>
    <citation>Tepper SJ. A pivotal moment in 50 years of headache history: the first American Migraine Study. Headache. 2008 May;48(5):730-1; discussion 732. doi: 10.1111/j.1526-4610.2008.01117_1.x.</citation>
    <PMID>18471125</PMID>
  </reference>
  <reference>
    <citation>Piagkou M, Demesticha T, Troupis T, Vlasis K, Skandalakis P, Makri A, Mazarakis A, Lappas D, Piagkos G, Johnson EO. The pterygopalatine ganglion and its role in various pain syndromes: from anatomy to clinical practice. Pain Pract. 2012 Jun;12(5):399-412. doi: 10.1111/j.1533-2500.2011.00507.x. Epub 2011 Sep 29. Erratum In: Pain Pract. 2012 Nov;12(8):673.</citation>
    <PMID>21956040</PMID>
  </reference>
  <reference>
    <citation>Oluigbo CO, Makonnen G, Narouze S, Rezai AR. Sphenopalatine ganglion interventions: technical aspects and application. Prog Neurol Surg. 2011;24:171-179. doi: 10.1159/000323049. Epub 2011 Mar 21.</citation>
    <PMID>21422787</PMID>
  </reference>
  <reference>
    <citation>Windsor RE, Jahnke S. Sphenopalatine ganglion blockade: a review and proposed modification of the transnasal technique. Pain Physician. 2004 Apr;7(2):283-6.</citation>
    <PMID>16868606</PMID>
  </reference>
  <reference>
    <citation>Rosenberg M, Phero JC. Regional anesthesia and invasive techniques to manage head and neck pain. Otolaryngol Clin North Am. 2003 Dec;36(6):1201-19. doi: 10.1016/s0030-6665(03)00134-8.</citation>
    <PMID>15025017</PMID>
  </reference>
  <reference>
    <citation>Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May;8(5):781-97. doi: 10.1586/14737175.8.5.781.</citation>
    <PMID>18457535</PMID>
  </reference>
  <reference>
    <citation>Boivie J. Chapter 48 Central post-stroke pain. Handb Clin Neurol. 2006;81:715-30. doi: 10.1016/S0072-9752(06)80052-7. No abstract available.</citation>
    <PMID>18808870</PMID>
  </reference>
  <reference>
    <citation>Stankewitz A, Voit HL, Bingel U, Peschke C, May A. A new trigemino-nociceptive stimulation model for event-related fMRI. Cephalalgia. 2010 Apr;30(4):475-85. doi: 10.1111/j.1468-2982.2009.01968.x. Epub 2010 Feb 1.</citation>
    <PMID>19673914</PMID>
  </reference>
  <reference>
    <citation>Herrera Tolosana S, Fernandez Liesa R, Escolar Castellon Jde D, Perez Delgado L, Lisbona Alquezar MP, Tejero-Garces Galve G, Guallar Larpa M, Ortiz Garcia A. [Sphenopalatinum foramen: an anatomical study]. Acta Otorrinolaringol Esp. 2011 Jul-Aug;62(4):274-8. doi: 10.1016/j.otorri.2011.01.009. Epub 2011 Mar 22. Spanish.</citation>
    <PMID>21429469</PMID>
  </reference>
  <reference>
    <citation>Rusu MC. Microanatomy of the neural scaffold of the pterygopalatine fossa in humans: trigeminovascular projections and trigeminal-autonomic plexuses. Folia Morphol (Warsz). 2010 May;69(2):84-91.</citation>
    <PMID>20512758</PMID>
  </reference>
  <reference>
    <citation>Oomen KP, Ebbeling M, de Ru JA, Hordijk GJ, Bleys RL. A previously undescribed branch of the pterygopalatine ganglion. Am J Rhinol Allergy. 2011 Jan-Feb;25(1):50-3. doi: 10.2500/ajra.2011.25.3550.</citation>
    <PMID>21711979</PMID>
  </reference>
  <reference>
    <citation>Siessere S, Vitti M, Sousa LG, Semprini M, Iyomasa MM, Regalo SC. Anatomic variation of cranial parasympathetic ganglia. Braz Oral Res. 2008 Apr-Jun;22(2):101-5. doi: 10.1590/s1806-83242008000200002.</citation>
    <PMID>18622477</PMID>
  </reference>
  <reference>
    <citation>Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90. doi: 10.1212/01.wnl.0000326598.83183.04. Epub 2008 Aug 20.</citation>
    <PMID>18716236</PMID>
  </reference>
  <reference>
    <citation>Yang lY, Oraee S. A novel approach to transnasal sphenopalatine ganglion injection. Pain Physician. 2006 Apr;9(2):131-4.</citation>
    <PMID>16703973</PMID>
  </reference>
  <reference>
    <citation>Kanai A, Suzuki A, Kobayashi M, Hoka S. Intranasal lidocaine 8% spray for second-division trigeminal neuralgia. Br J Anaesth. 2006 Oct;97(4):559-63. doi: 10.1093/bja/ael180. Epub 2006 Aug 1.</citation>
    <PMID>16882684</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>July 24, 2014</results_first_submitted>
  <results_first_submitted_qc>October 10, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 20, 2014</results_first_posted>
  <last_update_submitted>January 25, 2018</last_update_submitted>
  <last_update_submitted_qc>January 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Headache</keyword>
  <keyword>Chronic Migraine</keyword>
  <keyword>Marcaine</keyword>
  <keyword>Tx360</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Marcaine</title>
          <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
        </group>
        <group group_id="P2">
          <title>Saline</title>
          <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Marcaine</title>
          <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
        </group>
        <group group_id="B2">
          <title>Saline</title>
          <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</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="27"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="41"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.96" spread="11.63"/>
                    <measurement group_id="B2" value="41.97" spread="14.71"/>
                    <measurement group_id="B3" value="41.30" spread="12.59"/>
                  </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="20"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Numeric Rating Scale (NRS)</title>
        <description>Compare Numeric Rating Scale (NRS) scores Before Procedure,15-Minute Post Treatment, 30-Minutes Post Treatment, 24-Hour Post Treatment for all 12 treatments (Marcaine vs. Saline). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain. For each individual time point, all 12 treatments were averaged for that time point and a single value was used for comparison between the two groups.</description>
        <time_frame>6 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
          </group>
        </group_list>
        <measure>
          <title>Numeric Rating Scale (NRS)</title>
          <description>Compare Numeric Rating Scale (NRS) scores Before Procedure,15-Minute Post Treatment, 30-Minutes Post Treatment, 24-Hour Post Treatment for all 12 treatments (Marcaine vs. Saline). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain. For each individual time point, all 12 treatments were averaged for that time point and a single value was used for comparison between the two groups.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Before Procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.18" spread="2.79"/>
                    <measurement group_id="O2" value="3.78" spread="2.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 Minutes Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.53" spread="2.61"/>
                    <measurement group_id="O2" value="3.51" spread="2.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 Minutes Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.41" spread="2.61"/>
                    <measurement group_id="O2" value="3.45" spread="2.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 Hours Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.85" spread="2.74"/>
                    <measurement group_id="O2" value="4.20" spread="2.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Numeric Rating Scale (NRS)</title>
        <description>Compare percentage change in Numeric Rating Scale (NRS) score from Before Procedure to 15-Minutes, Before Procedure to 30-Minutes, Before Procedure to 24-Hours After Procedure for all 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain.</description>
        <time_frame>15 Minutes Post Treatment, 30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.&#xD;
Saline: Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Numeric Rating Scale (NRS)</title>
          <description>Compare percentage change in Numeric Rating Scale (NRS) score from Before Procedure to 15-Minutes, Before Procedure to 30-Minutes, Before Procedure to 24-Hours After Procedure for all 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain.</description>
          <units>percentage of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>15 Minutes Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.3" spread="34.5"/>
                    <measurement group_id="O2" value="-4.31" spread="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 Minutes Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-27.7" spread="37.1"/>
                    <measurement group_id="O2" value="-5.41" spread="29.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 Hours Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.5" spread="69.9"/>
                    <measurement group_id="O2" value="13.5" spread="78.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient's Global Impression of Change (PGIC)</title>
        <description>Compare 24-Hour After Procedure Patient's Global Impression of Change (PGIC) score for 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). PGIC is a likert scale ranging from 1 to 7 with 1 being very much improved and 7 being very much worse.</description>
        <time_frame>30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.&#xD;
Saline: Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Patient's Global Impression of Change (PGIC)</title>
          <description>Compare 24-Hour After Procedure Patient's Global Impression of Change (PGIC) score for 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). PGIC is a likert scale ranging from 1 to 7 with 1 being very much improved and 7 being very much worse.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 Minutes Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" spread="1.02"/>
                    <measurement group_id="O2" value="3.72" spread="0.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 Hours Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.08" spread="1.26"/>
                    <measurement group_id="O2" value="3.88" spread="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Modified Pain Characteristic Questionnaire</title>
        <description>Compare Modified Pain Characteristic Questionnaire scores Before Procedure vs. 24-Hour After Procedure, Before Procedure vs. 1-Month Follow Up, and Before Procedure vs. 6-Month Follow Up (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). The modified pain characteristic questionnaire is a series of 11 questions on a likert scale ranging from 0 to 10 with 0 being no pain or does not interfere and 10 being worst pain or completely interferes. Percentage questions range from 0 to 100.</description>
        <time_frame>Before Treatment, 24 Hours After Treatment, 1 Month Post Treatment, and 6 Months Post Treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
          </group>
        </group_list>
        <measure>
          <title>Modified Pain Characteristic Questionnaire</title>
          <description>Compare Modified Pain Characteristic Questionnaire scores Before Procedure vs. 24-Hour After Procedure, Before Procedure vs. 1-Month Follow Up, and Before Procedure vs. 6-Month Follow Up (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). The modified pain characteristic questionnaire is a series of 11 questions on a likert scale ranging from 0 to 10 with 0 being no pain or does not interfere and 10 being worst pain or completely interferes. Percentage questions range from 0 to 100.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Worst Pain Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.75" spread="3.11"/>
                    <measurement group_id="O2" value="6.15" spread="2.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worst Pain Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.36" spread="3.01"/>
                    <measurement group_id="O2" value="6.16" spread="2.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worst Pain Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.56" spread="3.23"/>
                    <measurement group_id="O2" value="5.64" spread="3.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worst Pain Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.27" spread="3.10"/>
                    <measurement group_id="O2" value="5.88" spread="1.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Least Pain Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.01" spread="2.55"/>
                    <measurement group_id="O2" value="2.50" spread="2.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Least Pain Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.77" spread="2.49"/>
                    <measurement group_id="O2" value="2.43" spread="1.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Least Pain Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.88" spread="2.62"/>
                    <measurement group_id="O2" value="2.64" spread="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Least Pain Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.68" spread="2.03"/>
                    <measurement group_id="O2" value="2.88" spread="2.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average Pain Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.39" spread="2.61"/>
                    <measurement group_id="O2" value="4.33" spread="2.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average Pain Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.07" spread="2.57"/>
                    <measurement group_id="O2" value="4.27" spread="2.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average Pain Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.36" spread="2.87"/>
                    <measurement group_id="O2" value="3.91" spread="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average Pain Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.86" spread="2.62"/>
                    <measurement group_id="O2" value="4.00" spread="2.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percent Relief Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.3" spread="36.5"/>
                    <measurement group_id="O2" value="29.2" spread="33.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percent Relief Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0" spread="38.2"/>
                    <measurement group_id="O2" value="29.8" spread="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percent Relief Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.3" spread="39.9"/>
                    <measurement group_id="O2" value="21.0" spread="32.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percent Relief Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.7" spread="29.2"/>
                    <measurement group_id="O2" value="18.6" spread="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General Activity Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.49" spread="2.96"/>
                    <measurement group_id="O2" value="3.50" spread="2.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General Activity Question: 24 Hours After Treatmen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.31" spread="2.90"/>
                    <measurement group_id="O2" value="3.64" spread="2.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General Activity Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.64" spread="2.91"/>
                    <measurement group_id="O2" value="3.91" spread="2.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General Activity Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.68" spread="2.87"/>
                    <measurement group_id="O2" value="4.00" spread="3.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mood Interference Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.57" spread="3.07"/>
                    <measurement group_id="O2" value="3.78" spread="2.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mood Interference Question: 24 Hours After Treatme</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.42" spread="3.06"/>
                    <measurement group_id="O2" value="4.19" spread="3.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mood Interference Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.96" spread="3.43"/>
                    <measurement group_id="O2" value="3.82" spread="3.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mood Interference Question: 6 Months Post Treatmen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.18" spread="3.26"/>
                    <measurement group_id="O2" value="5.71" spread="3.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Walking Ability Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.63" spread="1.27"/>
                    <measurement group_id="O2" value="1.27" spread="2.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Walking Ability Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" spread="1.33"/>
                    <measurement group_id="O2" value="1.24" spread="2.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Walking Ability Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.80" spread="1.68"/>
                    <measurement group_id="O2" value="0.55" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Walking Ability Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.45" spread="1.74"/>
                    <measurement group_id="O2" value="0.43" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Normal Work Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.53" spread="3.08"/>
                    <measurement group_id="O2" value="3.49" spread="2.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Normal Work Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.21" spread="3.02"/>
                    <measurement group_id="O2" value="3.63" spread="2.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Normal Work Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.52" spread="3.14"/>
                    <measurement group_id="O2" value="3.45" spread="2.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Normal Work Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.59" spread="2.77"/>
                    <measurement group_id="O2" value="3.71" spread="3.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relationships Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" spread="2.87"/>
                    <measurement group_id="O2" value="3.47" spread="2.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relationships Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.96" spread="2.87"/>
                    <measurement group_id="O2" value="3.90" spread="3.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relationships Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.36" spread="3.29"/>
                    <measurement group_id="O2" value="3.09" spread="3.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relationships Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.05" spread="2.87"/>
                    <measurement group_id="O2" value="3.86" spread="3.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Interference Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.29" spread="3.09"/>
                    <measurement group_id="O2" value="2.68" spread="3.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Interfere Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.89" spread="3.03"/>
                    <measurement group_id="O2" value="2.85" spread="3.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Interferenc Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.92" spread="3.00"/>
                    <measurement group_id="O2" value="2.55" spread="3.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Interference Question: 6 Months Post Treatme</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.55" spread="2.32"/>
                    <measurement group_id="O2" value="3.14" spread="3.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enjoyment Question: Before Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.81" spread="3.24"/>
                    <measurement group_id="O2" value="3.12" spread="2.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enjoyment Question: 24 Hours After Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.58" spread="3.29"/>
                    <measurement group_id="O2" value="3.34" spread="2.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enjoyment Question: 1 Month Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.64" spread="3.51"/>
                    <measurement group_id="O2" value="3.09" spread="2.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enjoyment Question: 6 Months Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.18" spread="3.36"/>
                    <measurement group_id="O2" value="4.00" spread="4.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Migraine Headache Days</title>
        <description>Compare change in the number of migraine headache days per month reported in Baseline Period Diary vs. Treatment Period Diary vs. Post-Treatment Period Diary.</description>
        <time_frame>12 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.&#xD;
Saline: Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Migraine Headache Days</title>
          <description>Compare change in the number of migraine headache days per month reported in Baseline Period Diary vs. Treatment Period Diary vs. Post-Treatment Period Diary.</description>
          <units>Migraine headache days per month</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.0" spread="6.33"/>
                    <measurement group_id="O2" value="15.8" spread="7.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" spread="8.83"/>
                    <measurement group_id="O2" value="12.2" spread="9.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8" spread="9.22"/>
                    <measurement group_id="O2" value="11.3" spread="8.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acute Medications Usage</title>
        <description>Number of acute medications used during Treatment period (6 weeks) and Follow-Up (4 weeks) (Group A vs. Group B).</description>
        <time_frame>10 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
          </group>
        </group_list>
        <measure>
          <title>Acute Medications Usage</title>
          <description>Number of acute medications used during Treatment period (6 weeks) and Follow-Up (4 weeks) (Group A vs. Group B).</description>
          <units>Number of medications used</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.3" spread="28.2"/>
                    <measurement group_id="O2" value="47.4" spread="54.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events</title>
        <description>Number of adverse events over the entire length of study (Group A vs. Group B).</description>
        <time_frame>34 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events</title>
          <description>Number of adverse events over the entire length of study (Group A vs. Group B).</description>
          <units>Number of Adverse Events</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.67" spread="8.23"/>
                    <measurement group_id="O2" value="5.29" spread="7.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Headache Impact Test (HIT-6)</title>
        <description>Total Headache Impact Test (HIT-6) scores Pre-Treatment at Visit 2 vs. Post-Treatment (following final treatment), and at 1-Month Post-Treatment (Group A vs. Group B). HIT-6 is a series of 6 likert scale questions ranging from 1 to 5 with 1 being never and 5 being always. The HIT-6 answer options are weighted as follows: Never (1) = 6 points each, Rarely (2) = 9 points each, Sometimes (3) = 10 points each, Very often (4) = 11 points each, Always (5) = 13 points each. The total score for the HIT-6 ranges from 36 (subject answers all 6 questions as &quot;Never&quot;) to 78 subject answers all 6 questions as &quot;Always&quot;), with higher total scores indicating more impact than lower scores, i.e., headaches cause greater impact on the subject's life.</description>
        <time_frame>10 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
          </group>
        </group_list>
        <measure>
          <title>Headache Impact Test (HIT-6)</title>
          <description>Total Headache Impact Test (HIT-6) scores Pre-Treatment at Visit 2 vs. Post-Treatment (following final treatment), and at 1-Month Post-Treatment (Group A vs. Group B). HIT-6 is a series of 6 likert scale questions ranging from 1 to 5 with 1 being never and 5 being always. The HIT-6 answer options are weighted as follows: Never (1) = 6 points each, Rarely (2) = 9 points each, Sometimes (3) = 10 points each, Very often (4) = 11 points each, Always (5) = 13 points each. The total score for the HIT-6 ranges from 36 (subject answers all 6 questions as &quot;Never&quot;) to 78 subject answers all 6 questions as &quot;Always&quot;), with higher total scores indicating more impact than lower scores, i.e., headaches cause greater impact on the subject's life.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.36" spread="4.93"/>
                    <measurement group_id="O2" value="64" spread="3.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.85" spread="8.33"/>
                    <measurement group_id="O2" value="62.5" spread="4.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1-Month Post-Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.23" spread="8.97"/>
                    <measurement group_id="O2" value="61.92" spread="5.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Satisfaction</title>
        <description>Satisfaction scores Visit 2 vs. following treatment (Treatment 12) and at 1-Month Post-Treatment (Group A vs. Group B). Satisfaction scores are a likert scale ranging from 1 to 5 with 1 being complete dissatisfaction and 5 being complete satisfaction.</description>
        <time_frame>10 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Marcaine</title>
            <description>Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Satisfaction</title>
          <description>Satisfaction scores Visit 2 vs. following treatment (Treatment 12) and at 1-Month Post-Treatment (Group A vs. Group B). Satisfaction scores are a likert scale ranging from 1 to 5 with 1 being complete dissatisfaction and 5 being complete satisfaction.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.52" spread="0.75"/>
                    <measurement group_id="O2" value="3.00" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following treatment (Treatment 12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.55" spread="1.00"/>
                    <measurement group_id="O2" value="2.50" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1-Month Post-Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.57" spread="0.99"/>
                    <measurement group_id="O2" value="2.64" spread="1.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time of signing the informed consent until study exit. The length of study participation was 34 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Marcaine</title>
          <description>Marcaine (Group A) will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)&#xD;
Marcaine: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.</description>
        </group>
        <group group_id="E2">
          <title>Saline</title>
          <description>Saline (Group B) will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <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="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary Embolism Resulting in Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Ringing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation</sub_title>
                <counts group_id="E1" events="58" subjects_affected="8" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Bad Taste</sub_title>
                <counts group_id="E1" events="30" subjects_affected="7" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Mouth Numbness</sub_title>
                <counts group_id="E1" events="37" subjects_affected="6" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nasal Irritation</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Light Headedness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cold</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </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>Jim Sly</name_or_title>
      <organization>Clinvest Research</organization>
      <phone>4178413673</phone>
      <email>jsly@clinvest.com</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/NCT01709708
org study id: 12-004TI
nct id: NCT01709708
lead sponsor: 
collaborator: 
has dmc: Yes
Migraine imposes a substantial burden on patients in terms of diminished daily functioning,
      quality of life, and financial loss. Pain severity and duration correlates with reduced
      measures of daily functioning, and overall health status. The sphenopalatine ganglion (SPG)
      has been implicated in a variety of cephalalgias. This has been well represented in the
      literature dating back over a century. Access to this structure can be gained via a small
      area of mucosa just posterior and superior to the tail of the middle turbinate on the lateral
      nasal wall. At this aspect, there is no bony boundary to the SPG. Blocking the SPG using
      local anesthetics relieves pain. Unfortunately, many current interventions are cumbersome,
      invasive, and expensive. The purpose of this study is to evaluate the efficacy of the Tx360™,
      a new nasal applicator device, in the treatment of head and face pain and to examine the
      economic implications. The Tx360™ is a single use device designed to deliver a topical local
      anesthetic to the specific area of mucosa associated with the SPG. A total of 42 study
      participants will be accepted into this double-blind placebo-controlled study. 28 will
      receive SPG blocks using a 0.3 mL of a 0.5% solution of Marcaine delivered by the Tx360™
      while 14 will receive a placebo of saline substituted for the Marcaine. Both patient sets
      will also be given a piece of lemon hard candy as a taste distractor. Participants must have
      a chronic migraine history with over 15 symptomatic days per month over the past three
      months. The treatment plan consists of six weeks of treatment, two times per week. Short and
      longer term assessments will be retrieved and analyzed as detailed in the Study Design.
42 study participants will be included in this double-blind placebo-controlled study.
      Following enrollment of 42 subjects and completion of the 6-week Treatment Period by all
      active subjects, an analysis of the treatment effect will be performed for a reassessment of
      sample size and, if deemed appropriate, the study will continue with enrollment of additional
      subjects to ensure a more statistically robust interpretation of the data. The results of the
      statistical analysis will be blinded from Investigators and coordinators. The procedure will
      be delivered to all subjects who agree to participate, meet inclusion criteria, and sign
      informed consent.

      At Visit 1 following Informed Consent, a physical exam and vital signs will be completed. A
      medical, headache, and medication history (to include age, sex, height and weight, and
      duration and location of headache pain, as well as history of ER visits) will be collected on
      all subjects. Eligible subjects will be provided with a Baseline Headache Diary and
      instructed to treat migraines for the following month in their usual manner with their usual
      treatment. The daily Diary will document headache, acute treatment and response, and migraine
      associated symptoms (nausea, vomiting, light sensitivity, or sound sensitivity) to establish
      a Baseline number of headache days and severity. Visit 2 will be scheduled for 1 month
      following Visit 1. Following Visit 1, Visits 2-13 (treatment visits) will be scheduled to
      occur twice weekly (during the regular Monday - Friday work week) at least 2 days apart.
      Treatments should not occur on consecutive days.

      At Visit 2, the Baseline Headache Diary will be reviewed and those subjects continuing to
      meet eligibility will be dispensed a 6-week Treatment Period Diary and complete Before
      Procedure questions to include the Pain Intensity Numeric Rating Scale (NRS), the Modified
      Pain Characteristic Questionnaire, and a baseline Headache Impact Test-6 (HIT-6), have vital
      signs completed, and the medical, headache, and medication history updated. Subjects will be
      randomized 2:1 to Group A or Group B. Group A will receive treatment with 0.3 mL of 0.5%
      Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the SPG.
      Group B will receive saline substituted for Marcaine delivered bilaterally with the Tx360TM
      device to the mucosa associated with the SPG.

      To maintain the blinding of the treatment groups, neither the Investigator nor research
      personnel who are involved in evaluating the subject should prepare the study medication. An
      independent research staff person with no involvement in the study conduct will place study
      medication (either Marcaine for a subject randomized to Group A or Placebo/saline for a
      subject randomized to Group B) in a 1cc Luer Lok tip syringe and assemble the syringe and
      Tx360TM catheter as instructed in training. A label with the subject Drug Number will be
      placed on the device at that time. The research staff person administering the study
      medication will verify that the Drug Number assignment is correct.

      Both Groups will be given a piece of lemon hard candy as a taste distractor.

      At each treatment visit (Visits 2-13), in addition to Before Procedure questions, subjects
      will complete 15-minute and 30-minute After Procedure questionnaires to include the NRS and,
      at 30 minutes, the Patient's Global Impression of Change (PGIC). Subjects will take home a
      questionnaire to include the NRS, PGIC, satisfaction question, and the Modified Pain
      Characteristic Questionnaire to be completed at 24 hours following treatment and be
      instructed to return the 24-hour After Procedure questionnaire to the clinic at the next
      visit.

      At Visits 2-15 vital signs will be completed, medications will be updated, and Non-Serious
      Adverse Events will be collected after the first treatment. Serious Adverse Events will be
      collected once the informed consent has been signed and throughout the study.

      At Visits 5, 8, and 11, the Treatment Period Headache Diary will be collected, reviewed, and
      re-dispensed.

      At Visit 13, the 1-Month Post-Treatment Period Diary will be dispensed.

      The subject will return to the clinic at Visit 14 between 24 and 96 hours following the final
      treatment at Visit 13 to return the 24-hour After Procedure Questionnaire and complete the
      1-Month Treatment Period HIT-6. The Treatment Period Diary will be collected.

      At Visit 15, 1 month following the final treatment, each subject will return to the clinic
      and complete a 1-Month Follow Up HIT-6 and the 1-Month Follow Up Questionnaire. The 1-Month
      Post-Treatment Period Diary will be collected.

      At 6 months following the final treatment, each subject will be phoned to complete the
      6-Month Follow Up Questionnaire to include the NRS, PGIC, satisfaction question, the Modified
      Pain Characteristic Questionnaire, and a 6-Month Follow Up HIT-6.

      Treatment Medication Subjects randomized to Group A will be administered 0.3 mL of 0.5%
      Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the SPG.
      Twelve treatments will be administered over a period of 6 weeks.

      Subjects randomized to Group B will be administered saline substituted for Marcaine delivered
      bilaterally with the Tx360TM device to the mucosa associated with the SPG for treatment of
      chronic migraine. Twelve treatments will be administered over a period of 6 weeks.

      Rescue Medication Subjects will be allowed to rescue with medication mutually agreed upon by
      subject and Investigator at the time of screening.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Numeric Rating Scale (NRS)
time frame: 6 Weeks
description: Compare Numeric Rating Scale (NRS) scores Before Procedure,15-Minute Post Treatment, 30-Minutes Post Treatment, 24-Hour Post Treatment for all 12 treatments (Marcaine vs. Saline). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain. For each individual time point, all 12 treatments were averaged for that time point and a single value was used for comparison between the two groups.
measure: Change in Numeric Rating Scale (NRS)
time frame: 15 Minutes Post Treatment, 30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks
description: Compare percentage change in Numeric Rating Scale (NRS) score from Before Procedure to 15-Minutes, Before Procedure to 30-Minutes, Before Procedure to 24-Hours After Procedure for all 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain.
measure: Patient's Global Impression of Change (PGIC)
time frame: 30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks
description: Compare 24-Hour After Procedure Patient's Global Impression of Change (PGIC) score for 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). PGIC is a likert scale ranging from 1 to 7 with 1 being very much improved and 7 being very much worse.
measure: Modified Pain Characteristic Questionnaire
time frame: Before Treatment, 24 Hours After Treatment, 1 Month Post Treatment, and 6 Months Post Treatment
description: Compare Modified Pain Characteristic Questionnaire scores Before Procedure vs. 24-Hour After Procedure, Before Procedure vs. 1-Month Follow Up, and Before Procedure vs. 6-Month Follow Up (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). The modified pain characteristic questionnaire is a series of 11 questions on a likert scale ranging from 0 to 10 with 0 being no pain or does not interfere and 10 being worst pain or completely interferes. Percentage questions range from 0 to 100.
measure: Migraine Headache Days
time frame: 12 Weeks
description: Compare change in the number of migraine headache days per month reported in Baseline Period Diary vs. Treatment Period Diary vs. Post-Treatment Period Diary.
measure: Acute Medications Usage
time frame: 10 Weeks
description: Number of acute medications used during Treatment period (6 weeks) and Follow-Up (4 weeks) (Group A vs. Group B).
measure: Adverse Events
time frame: 34 weeks
description: Number of adverse events over the entire length of study (Group A vs. Group B).
measure: Headache Impact Test (HIT-6)
time frame: 10 Weeks
description: Total Headache Impact Test (HIT-6) scores Pre-Treatment at Visit 2 vs. Post-Treatment (following final treatment), and at 1-Month Post-Treatment (Group A vs. Group B). HIT-6 is a series of 6 likert scale questions ranging from 1 to 5 with 1 being never and 5 being always. The HIT-6 answer options are weighted as follows: Never (1) = 6 points each, Rarely (2) = 9 points each, Sometimes (3) = 10 points each, Very often (4) = 11 points each, Always (5) = 13 points each. The total score for the HIT-6 ranges from 36 (subject answers all 6 questions as "Never") to 78 subject answers all 6 questions as "Always"), with higher total scores indicating more impact than lower scores, i.e., headaches cause greater impact on the subject's life.
measure: Overall Satisfaction
time frame: 10 Weeks
description: Satisfaction scores Visit 2 vs. following treatment (Treatment 12) and at 1-Month Post-Treatment (Group A vs. Group B). Satisfaction scores are a likert scale ranging from 1 to 5 with 1 being complete dissatisfaction and 5 being complete satisfaction.
arm group label: Marcaine
arm group type: Active Comparator
description: Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)
arm group label: Saline
arm group type: Placebo Comparator
description: Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.
intervention type: Drug
intervention name: Marcaine
description: Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.
arm group label: Marcaine
other name: Bupivicane (generic)
intervention type: Drug
intervention name: Saline
description: Saline
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Tian Xia, MD
role: Principal Investigator
affiliation: Tian Medical Inc.
facility: 
facility: 
country: United States
url: http://www.tianmedical.com
description: Instructions for use and device training
citation: Tepper SJ. A pivotal moment in 50 years of headache history: the first American Migraine Study. Headache. 2008 May;48(5):730-1; discussion 732. doi: 10.1111/j.1526-4610.2008.01117_1.x.
PMID: 18471125
citation: Piagkou M, Demesticha T, Troupis T, Vlasis K, Skandalakis P, Makri A, Mazarakis A, Lappas D, Piagkos G, Johnson EO. The pterygopalatine ganglion and its role in various pain syndromes: from anatomy to clinical practice. Pain Pract. 2012 Jun;12(5):399-412. doi: 10.1111/j.1533-2500.2011.00507.x. Epub 2011 Sep 29. Erratum In: Pain Pract. 2012 Nov;12(8):673.
PMID: 21956040
citation: Oluigbo CO, Makonnen G, Narouze S, Rezai AR. Sphenopalatine ganglion interventions: technical aspects and application. Prog Neurol Surg. 2011;24:171-179. doi: 10.1159/000323049. Epub 2011 Mar 21.
PMID: 21422787
citation: Windsor RE, Jahnke S. Sphenopalatine ganglion blockade: a review and proposed modification of the transnasal technique. Pain Physician. 2004 Apr;7(2):283-6.
PMID: 16868606
citation: Rosenberg M, Phero JC. Regional anesthesia and invasive techniques to manage head and neck pain. Otolaryngol Clin North Am. 2003 Dec;36(6):1201-19. doi: 10.1016/s0030-6665(03)00134-8.
PMID: 15025017
citation: Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May;8(5):781-97. doi: 10.1586/14737175.8.5.781.
PMID: 18457535
citation: Boivie J. Chapter 48 Central post-stroke pain. Handb Clin Neurol. 2006;81:715-30. doi: 10.1016/S0072-9752(06)80052-7. No abstract available.
PMID: 18808870
citation: Stankewitz A, Voit HL, Bingel U, Peschke C, May A. A new trigemino-nociceptive stimulation model for event-related fMRI. Cephalalgia. 2010 Apr;30(4):475-85. doi: 10.1111/j.1468-2982.2009.01968.x. Epub 2010 Feb 1.
PMID: 19673914
citation: Herrera Tolosana S, Fernandez Liesa R, Escolar Castellon Jde D, Perez Delgado L, Lisbona Alquezar MP, Tejero-Garces Galve G, Guallar Larpa M, Ortiz Garcia A. [Sphenopalatinum foramen: an anatomical study]. Acta Otorrinolaringol Esp. 2011 Jul-Aug;62(4):274-8. doi: 10.1016/j.otorri.2011.01.009. Epub 2011 Mar 22. Spanish.
PMID: 21429469
citation: Rusu MC. Microanatomy of the neural scaffold of the pterygopalatine fossa in humans: trigeminovascular projections and trigeminal-autonomic plexuses. Folia Morphol (Warsz). 2010 May;69(2):84-91.
PMID: 20512758
citation: Oomen KP, Ebbeling M, de Ru JA, Hordijk GJ, Bleys RL. A previously undescribed branch of the pterygopalatine ganglion. Am J Rhinol Allergy. 2011 Jan-Feb;25(1):50-3. doi: 10.2500/ajra.2011.25.3550.
PMID: 21711979
citation: Siessere S, Vitti M, Sousa LG, Semprini M, Iyomasa MM, Regalo SC. Anatomic variation of cranial parasympathetic ganglia. Braz Oral Res. 2008 Apr-Jun;22(2):101-5. doi: 10.1590/s1806-83242008000200002.
PMID: 18622477
citation: Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90. doi: 10.1212/01.wnl.0000326598.83183.04. Epub 2008 Aug 20.
PMID: 18716236
citation: Yang lY, Oraee S. A novel approach to transnasal sphenopalatine ganglion injection. Pain Physician. 2006 Apr;9(2):131-4.
PMID: 16703973
citation: Kanai A, Suzuki A, Kobayashi M, Hoka S. Intranasal lidocaine 8% spray for second-division trigeminal neuralgia. Br J Anaesth. 2006 Oct;97(4):559-63. doi: 10.1093/bja/ael180. Epub 2006 Aug 1.
PMID: 16882684
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Bupivacaine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 