<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/NCT02258217</url>
  </required_header>
  <id_info>
    <org_study_id>2014H0156</org_study_id>
    <nct_id>NCT02258217</nct_id>
  </id_info>
  <brief_title>Tolerability of Acthar for the Treatment of Multiple Sclerosis in Relapses (TAMS)</brief_title>
  <official_title>Tolerability of Acthar for the Treatment of Multiple Sclerosis Relapses (TAMS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OhioHealth</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>OhioHealth</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Tolerability of Acthar for the Treatment of Multiple Sclerosis Relapses (TAMS)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We propose to conduct a prospective, single-center, open-label, single-arm study comparing&#xD;
      tolerability of Acthar versus oral prednisone in the treatment of MS relapses. Potential&#xD;
      subjects will be identified during routine clinical evaluations. If patient is determined to&#xD;
      be having a study-defined MS relapse, they will be invited to participate in this study.&#xD;
      After consent is obtained, the patient will complete the first page of the ARMS survey. If&#xD;
      prior steroid use was deemed tolerable then only the first page of the ARMS will be collected&#xD;
      and analyzed and these patients will complete their participation in the trial. Their data&#xD;
      from the ARMS will provide an estimate as to the number of patients who self-report&#xD;
      tolerability and efficacy issues with steroids. However, if patients self-report prior&#xD;
      steroid intolerability, then they will advance into the Acthar treatment arm of the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">June 24, 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living)</measure>
    <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
    <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, history of patients from the survey after treatment for the new relapse will be collected.&#xD;
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
ADL scores were calculated from Part 1 (new relapse), question 3 and Part 2 (after treatment of relapse), question 5 both specifically refer to ADL;&#xD;
Scale: ADL (Activities of Daily Living) Minimum value: 0 Maximum value: 9 Higher scores indicated better functioning/ improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health)</measure>
    <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
    <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
Part 1 (new relapse) &amp; Part 2 (after treatment of new relapse), question 6 were used to calculate RSH;&#xD;
Scale: RSH (Return to previous health) Minimum value: -1 Maximum value: 10 Higher scores indicating a more complete return to previous state of health.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores)</measure>
    <time_frame>Follow-up visit</time_frame>
    <description>Patients completed the ARMS survey after treatment for the new relapse.The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
The TCS score was calculated only for the time point after treatment of relapse. It was a sum of questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. Scores range from 0 to 30 units, with higher scores representing greater improvement/better functioning.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores)</measure>
    <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
    <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse.&#xD;
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
PCS was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; Higher scores indicating better functioning/greater improvement. The PCS scores were on a scale of 0 to 20 units.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score</measure>
    <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
    <description>The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS.&#xD;
The physical impact of MS was compared between pre and post phase using paired t-tests. Each question is answered with points ranging from 1 to 5. Higher score indicates worse outcome. The total MSIS physical score ranges from 20 to 100 points with lower points indicating better impact.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score.</measure>
    <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
    <description>The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS and 9 questions assess the psychological impact of MS.&#xD;
The psychological impact of MS was compared between pre and post phase using paired t-tests.&#xD;
The psychological impact of MS was compared between pre and post phase using paired t-tests.&#xD;
The score was on a scale of 9 to 45 points for MSIS psychological score.&#xD;
Higher score indicate worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>EDSS (Expanded Disability Status Scale) Scores.</measure>
    <time_frame>baseline and at follow-up</time_frame>
    <description>This scaling score is obtained by performing a neurologic exam with specific attention to eight different neurologic functional systems: visual, pyramidal, cerebellar, bowel and bladder, cerebral, brainstem, sensory and other (10). The score is rated from zero (normal neurologic examination) to ten (death due to MS). This is the standard neurologic disability scale used in clinical trials for the evaluation of disability in patients with MS.&#xD;
These scores were compared between pre and post phase using paired t-tests.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SAGE (Self-administered Gerocognitive Exam) Scores</measure>
    <time_frame>baseline and follow-up</time_frame>
    <description>The Self-Administered Gerocognitive Exam (SAGE) is designed to detect early signs of cognitive, memory or thinking impairments. It evaluates your thinking abilities and helps physicians to know how well your brain is working.&#xD;
It consists of 12 questions which are scored at different scales. The final SAGE score is calculated as a sum of these 12 questions and it ranges from 0 to 22.&#xD;
Higher score indicates better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>GASE Scale Questionnaire (Generic Assessment of Side Effects)</measure>
    <time_frame>1 week</time_frame>
    <description>Patients who reported a history of poor corticosteroid tolerability will be placed on Acthar and GASE scale will be given to assess tolerability to Acthar.&#xD;
We listed the number of times a symptom was reported and was attributable to the ACTHAR treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Relapsing Remitting Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Single arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acthar 80 units subcutaneously for five consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acthar</intervention_name>
    <description>Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
    <arm_group_label>Single arm</arm_group_label>
    <other_name>repository corticotropin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects who have volunteered and consented to participate in the study.&#xD;
&#xD;
          2. Subjects who have no contraindication to taking high dose, oral prednisone or Acthar.&#xD;
&#xD;
          3. Male or Female subjects age 18 or greater years of age.&#xD;
&#xD;
          4. Subjects with Relapsing Remitting Multiple Sclerosis (RRMS) based on 2010 McDonald&#xD;
             Criteria.&#xD;
&#xD;
          5. Subjects without an active infection (Note: If a patient is found to have an&#xD;
             uncomplicated UTI and agrees to start on appropriate antibiotic treatment, they can&#xD;
             continue in the study).&#xD;
&#xD;
          6. Subjects who are experiencing a protocol defined MS relapse within two weeks of&#xD;
             relapse onset.&#xD;
&#xD;
          7. Subjects who are able and willing to sign a consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects who are less than 18 years of age.&#xD;
&#xD;
          2. Subjects with any contraindication to taking Acthar.&#xD;
&#xD;
          3. Subjects with an active infection other than an uncomplicated urinary tract infection&#xD;
             (UTI) (subjects determined to have a UTI who agree to be treated with appropriate&#xD;
             antibiotics will not be excluded).&#xD;
&#xD;
          4. Subjects with an immune deficiency.&#xD;
&#xD;
          5. Subjects with a history of any of the following conditions: gastrointestinal ulcers,&#xD;
             diabetes mellitus, gestational diabetes, malignant hypertension or steroid induced&#xD;
             psychosis.&#xD;
&#xD;
          6. Subjects who are pregnant or breastfeeding.&#xD;
&#xD;
          7. Subjects who are unable or unwilling to sign consent form.&#xD;
&#xD;
          8. Patient is unable or unwilling to participate in phone and clinic follow up.&#xD;
&#xD;
          9. Other factors that in the opinion of the Principal Investigator would exclude the&#xD;
             subject from participation in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aaron L Boster, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OhioHealth</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OhioHealth</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Fox RJ, Bethoux F, Goldman MD, Cohen JA. Multiple sclerosis: advances in understanding, diagnosing, and treating the underlying disease. Cleve Clin J Med. 2006 Jan;73(1):91-102. doi: 10.3949/ccjm.73.1.91.</citation>
    <PMID>16444920</PMID>
  </reference>
  <reference>
    <citation>Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907-11. doi: 10.1212/wnl.46.4.907.</citation>
    <PMID>8780061</PMID>
  </reference>
  <reference>
    <citation>Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.</citation>
    <PMID>11006371</PMID>
  </reference>
  <reference>
    <citation>O'Brien JA, Ward AJ, Patrick AR, Caro J. Cost of managing an episode of relapse in multiple sclerosis in the United States. BMC Health Serv Res. 2003 Sep 2;3(1):17. doi: 10.1186/1472-6963-3-17.</citation>
    <PMID>12952552</PMID>
  </reference>
  <reference>
    <citation>Barnes D, Hughes RA, Morris RW, Wade-Jones O, Brown P, Britton T, Francis DA, Perkin GD, Rudge P, Swash M, Katifi H, Farmer S, Frankel J. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997 Mar 29;349(9056):902-6. doi: 10.1016/s0140-6736(96)06453-7.</citation>
    <PMID>9093250</PMID>
  </reference>
  <reference>
    <citation>Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology. 2004 Sep 28;63(6):1079-80. doi: 10.1212/01.wnl.0000138572.82125.f5.</citation>
    <PMID>15452302</PMID>
  </reference>
  <reference>
    <citation>La Mantia L, Eoli M, Milanese C, Salmaggi A, Dufour A, Torri V. Double-blind trial of dexamethasone versus methylprednisolone in multiple sclerosis acute relapses. Eur Neurol. 1994;34(4):199-203. doi: 10.1159/000117038.</citation>
    <PMID>7915989</PMID>
  </reference>
  <reference>
    <citation>Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2012 Dec 12;12:CD006921. doi: 10.1002/14651858.CD006921.pub3.</citation>
    <PMID>23235634</PMID>
  </reference>
  <reference>
    <citation>Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.</citation>
    <PMID>21387374</PMID>
  </reference>
  <reference>
    <citation>Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.</citation>
    <PMID>6685237</PMID>
  </reference>
  <reference>
    <citation>Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure. Brain. 2001 May;124(Pt 5):962-73. doi: 10.1093/brain/124.5.962.</citation>
    <PMID>11335698</PMID>
  </reference>
  <reference>
    <citation>Perrin Ross A, Williamson A, Smrtka J, Flemming Tracy T, Saunders C, Easterling C, Niewoehner J, Mutschler N. Assessing relapse in multiple sclerosis questionnaire: results of a pilot study. Mult Scler Int. 2013;2013:470476. doi: 10.1155/2013/470476. Epub 2013 May 26.</citation>
    <PMID>23766909</PMID>
  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <results_first_submitted>January 10, 2019</results_first_submitted>
  <results_first_submitted_qc>August 18, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 1, 2020</results_first_posted>
  <last_update_submitted>August 18, 2020</last_update_submitted>
  <last_update_submitted_qc>August 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adrenocorticotropic Hormone</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Single Arm</title>
          <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Single Arm</title>
          <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="38.4" spread="10.4"/>
                  </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="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living)</title>
        <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, history of patients from the survey after treatment for the new relapse will be collected.&#xD;
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
ADL scores were calculated from Part 1 (new relapse), question 3 and Part 2 (after treatment of relapse), question 5 both specifically refer to ADL;&#xD;
Scale: ADL (Activities of Daily Living) Minimum value: 0 Maximum value: 9 Higher scores indicated better functioning/ improvement.</description>
        <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living)</title>
          <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, history of patients from the survey after treatment for the new relapse will be collected.&#xD;
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
ADL scores were calculated from Part 1 (new relapse), question 3 and Part 2 (after treatment of relapse), question 5 both specifically refer to ADL;&#xD;
Scale: ADL (Activities of Daily Living) Minimum value: 0 Maximum value: 9 Higher scores indicated better functioning/ improvement.</description>
          <units>score 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="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ADL (new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ADL (after treatment of relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two ADL scores measured in the same arm at different timepoints (new &amp; after treatment).&#xD;
Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0&#xD;
We used the Paired t-test to compare the pre - post ADL scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in ADL score variable. This was calculated as follows:&#xD;
ADL score (new relapse) - ADL score (after treatment of current relapse)&#xD;
This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.003</p_value>
            <method>Paired t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.8</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>3.03</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.9</ci_lower_limit>
            <ci_upper_limit>-0.66</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health)</title>
        <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
Part 1 (new relapse) &amp; Part 2 (after treatment of new relapse), question 6 were used to calculate RSH;&#xD;
Scale: RSH (Return to previous health) Minimum value: -1 Maximum value: 10 Higher scores indicating a more complete return to previous state of health.</description>
        <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health)</title>
          <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
Part 1 (new relapse) &amp; Part 2 (after treatment of new relapse), question 6 were used to calculate RSH;&#xD;
Scale: RSH (Return to previous health) Minimum value: -1 Maximum value: 10 Higher scores indicating a more complete return to previous state of health.</description>
          <units>score 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>RSH (new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RSH (after treatment of new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two RSH scores measured in the same arm at different time points (new &amp; after treatment).&#xD;
Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0 We used the Paired t-test to compare the pre - post RSH scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in ADL score variable. This was calculated as follows:&#xD;
ADL score (new relapse) - ADL score (after treatment of current relapse) This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.99</p_value>
            <method>Paired t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>3.09</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.22</ci_lower_limit>
            <ci_upper_limit>1.22</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores)</title>
        <description>Patients completed the ARMS survey after treatment for the new relapse.The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
The TCS score was calculated only for the time point after treatment of relapse. It was a sum of questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. Scores range from 0 to 30 units, with higher scores representing greater improvement/better functioning.</description>
        <time_frame>Follow-up visit</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores)</title>
          <description>Patients completed the ARMS survey after treatment for the new relapse.The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
The TCS score was calculated only for the time point after treatment of relapse. It was a sum of questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. Scores range from 0 to 30 units, with higher scores representing greater improvement/better functioning.</description>
          <units>score 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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores)</title>
        <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse.&#xD;
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
PCS was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; Higher scores indicating better functioning/greater improvement. The PCS scores were on a scale of 0 to 20 units.</description>
        <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores)</title>
          <description>Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse.&#xD;
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.&#xD;
PCS was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; Higher scores indicating better functioning/greater improvement. The PCS scores were on a scale of 0 to 20 units.</description>
          <units>score 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PCS (New relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PCS (after treatment of relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two PCS scores measured in the same arm at different timepoints (new &amp; after treatment).&#xD;
Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0 We used the Paired t-test to compare the pre - post PCS scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in PCS score variable. This was calculated as follows:&#xD;
PCS score (new relapse) - PCS score (after treatment of current relapse). This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.03</p_value>
            <method>Paired t-test, two sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.9</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>4.42</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.67</ci_lower_limit>
            <ci_upper_limit>-0.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score</title>
        <description>The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS.&#xD;
The physical impact of MS was compared between pre and post phase using paired t-tests. Each question is answered with points ranging from 1 to 5. Higher score indicates worse outcome. The total MSIS physical score ranges from 20 to 100 points with lower points indicating better impact.</description>
        <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score</title>
          <description>The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS.&#xD;
The physical impact of MS was compared between pre and post phase using paired t-tests. Each question is answered with points ranging from 1 to 5. Higher score indicates worse outcome. The total MSIS physical score ranges from 20 to 100 points with lower points indicating better impact.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSIS physical (new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.5" lower_limit="23" upper_limit="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSIS physical (after treatment of new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56" lower_limit="20" upper_limit="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two MSIS physical scores measured in the same arm at different timepoints (new relapse &amp; after treatment of relapse).&#xD;
Null Hypothesis = Difference in medians is = 0 Alternate Hypothesis = Difference in medians is not = 0&#xD;
We used the Wilcoxon Signed rank test to compare the pre - post MSIS physical scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in MSIS physical score variable. This was calculated as follows:&#xD;
MSIS physical score (new relapse) - MSIS physical score (after treatment of current relapse)&#xD;
This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.19</p_value>
            <method>Wilcoxon Signed Rank test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>2.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score.</title>
        <description>The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS and 9 questions assess the psychological impact of MS.&#xD;
The psychological impact of MS was compared between pre and post phase using paired t-tests.&#xD;
The psychological impact of MS was compared between pre and post phase using paired t-tests.&#xD;
The score was on a scale of 9 to 45 points for MSIS psychological score.&#xD;
Higher score indicate worse outcome.</description>
        <time_frame>baseline visit &amp; follow-up after treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score.</title>
          <description>The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS and 9 questions assess the psychological impact of MS.&#xD;
The psychological impact of MS was compared between pre and post phase using paired t-tests.&#xD;
The psychological impact of MS was compared between pre and post phase using paired t-tests.&#xD;
The score was on a scale of 9 to 45 points for MSIS psychological score.&#xD;
Higher score indicate worse outcome.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSIS psychological(new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.4" lower_limit="12" upper_limit="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSIS psychological(after treatment of new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.3" lower_limit="9" upper_limit="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two MSIS psychological scores measured in the same arm at different timepoints (new relapse &amp; after treatment of relapse).&#xD;
Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0&#xD;
We used the Paired t-test to compare the pre - post MSIS psychological scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in MSIS psychological score variable. This was calculated as follows:&#xD;
MSIS psychological score (new relapse) - MSIS psychological score (after treatment of current relapse)&#xD;
This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.01</p_value>
            <method>Paired t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>3.1</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>6.3</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.74</ci_lower_limit>
            <ci_upper_limit>5.45</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>EDSS (Expanded Disability Status Scale) Scores.</title>
        <description>This scaling score is obtained by performing a neurologic exam with specific attention to eight different neurologic functional systems: visual, pyramidal, cerebellar, bowel and bladder, cerebral, brainstem, sensory and other (10). The score is rated from zero (normal neurologic examination) to ten (death due to MS). This is the standard neurologic disability scale used in clinical trials for the evaluation of disability in patients with MS.&#xD;
These scores were compared between pre and post phase using paired t-tests.</description>
        <time_frame>baseline and at follow-up</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>EDSS (Expanded Disability Status Scale) Scores.</title>
          <description>This scaling score is obtained by performing a neurologic exam with specific attention to eight different neurologic functional systems: visual, pyramidal, cerebellar, bowel and bladder, cerebral, brainstem, sensory and other (10). The score is rated from zero (normal neurologic examination) to ten (death due to MS). This is the standard neurologic disability scale used in clinical trials for the evaluation of disability in patients with MS.&#xD;
These scores were compared between pre and post phase using paired t-tests.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>EDSS score (new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="0" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>EDSS score (after treatment of new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="0" upper_limit="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two EDSS scores measured in the same arm at different timepoints (new relapse &amp; after treatment of relapse).&#xD;
Null Hypothesis = Difference in medians is = 0 Alternate Hypothesis = Difference in medians is not = 0&#xD;
We used the Wilcoxon Signed rank test to compare the pre - post EDSS scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in EDSS score variable. This was calculated as follows:&#xD;
EDSS score (new relapse) - EDSS score (after treatment of current relapse)&#xD;
This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.23</p_value>
            <method>Wilcoxon Signed Rank test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The interquartile range for the median difference in EDSS scores is 0.0 to 0.5</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>SAGE (Self-administered Gerocognitive Exam) Scores</title>
        <description>The Self-Administered Gerocognitive Exam (SAGE) is designed to detect early signs of cognitive, memory or thinking impairments. It evaluates your thinking abilities and helps physicians to know how well your brain is working.&#xD;
It consists of 12 questions which are scored at different scales. The final SAGE score is calculated as a sum of these 12 questions and it ranges from 0 to 22.&#xD;
Higher score indicates better outcome.</description>
        <time_frame>baseline and follow-up</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>SAGE (Self-administered Gerocognitive Exam) Scores</title>
          <description>The Self-Administered Gerocognitive Exam (SAGE) is designed to detect early signs of cognitive, memory or thinking impairments. It evaluates your thinking abilities and helps physicians to know how well your brain is working.&#xD;
It consists of 12 questions which are scored at different scales. The final SAGE score is calculated as a sum of these 12 questions and it ranges from 0 to 22.&#xD;
Higher score indicates better outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SAGE (new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21" lower_limit="14" upper_limit="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAGE (after treatment of new relapse)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21" lower_limit="15" upper_limit="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>We compared the two SAGE scores measured in the same arm at different time points (new relapse &amp; after treatment of relapse).&#xD;
Null Hypothesis = Difference in medians is = 0 Alternate Hypothesis = Difference in medians is not = 0&#xD;
We used the Wilcoxon Signed rank test to compare the pre - post SAGE scores.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>We created a difference in SAGE score variable. This was calculated as follows:&#xD;
SAGE score (new relapse) - SAGE score (after treatment of current relapse)&#xD;
This difference score was tested for equivalence to 0 or not.</non_inferiority_desc>
            <p_value>0.44</p_value>
            <method>Wilcoxon Signed Rank test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The interquartile range for the difference in medians is -1 to 0.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>GASE Scale Questionnaire (Generic Assessment of Side Effects)</title>
        <description>Patients who reported a history of poor corticosteroid tolerability will be placed on Acthar and GASE scale will be given to assess tolerability to Acthar.&#xD;
We listed the number of times a symptom was reported and was attributable to the ACTHAR treatment</description>
        <time_frame>1 week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm</title>
            <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
          </group>
        </group_list>
        <measure>
          <title>GASE Scale Questionnaire (Generic Assessment of Side Effects)</title>
          <description>Patients who reported a history of poor corticosteroid tolerability will be placed on Acthar and GASE scale will be given to assess tolerability to Acthar.&#xD;
We listed the number of times a symptom was reported and was attributable to the ACTHAR treatment</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dry Mouth</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tachycardia, palpitation or arrhythmia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Breathing problems</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reduced Appetite</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Increased appetite</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Difficulties with urination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin rash or itching</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tendency to develop bruises</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sweating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hot flashes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue, loss of energy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia, sleeping problems</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nightmares or abnormal dreams</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Back pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Agitation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irritability</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depressed Mood</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety, fearfulness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Further symptoms</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Single Arm</title>
          <description>Acthar 80 units subcutaneously for five consecutive days.&#xD;
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </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>Anand Gupta</name_or_title>
      <organization>OhioHealth Research Institute</organization>
      <phone>614-788-3868</phone>
      <email>anand.gupta@ohiohealth.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/NCT02258217
org study id: 2014H0156
nct id: NCT02258217
lead sponsor: 
has dmc: No
Tolerability of Acthar for the Treatment of Multiple Sclerosis Relapses (TAMS)
We propose to conduct a prospective, single-center, open-label, single-arm study comparing
      tolerability of Acthar versus oral prednisone in the treatment of MS relapses. Potential
      subjects will be identified during routine clinical evaluations. If patient is determined to
      be having a study-defined MS relapse, they will be invited to participate in this study.
      After consent is obtained, the patient will complete the first page of the ARMS survey. If
      prior steroid use was deemed tolerable then only the first page of the ARMS will be collected
      and analyzed and these patients will complete their participation in the trial. Their data
      from the ARMS will provide an estimate as to the number of patients who self-report
      tolerability and efficacy issues with steroids. However, if patients self-report prior
      steroid intolerability, then they will advance into the Acthar treatment arm of the trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living)
time frame: baseline visit & follow-up after treatment
description: Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, history of patients from the survey after treatment for the new relapse will be collected.
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.
ADL scores were calculated from Part 1 (new relapse), question 3 and Part 2 (after treatment of relapse), question 5 both specifically refer to ADL;
Scale: ADL (Activities of Daily Living) Minimum value: 0 Maximum value: 9 Higher scores indicated better functioning/ improvement.
measure: ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health)
time frame: baseline visit & follow-up after treatment
description: Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.
Part 1 (new relapse) & Part 2 (after treatment of new relapse), question 6 were used to calculate RSH;
Scale: RSH (Return to previous health) Minimum value: -1 Maximum value: 10 Higher scores indicating a more complete return to previous state of health.
measure: ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores)
time frame: Follow-up visit
description: Patients completed the ARMS survey after treatment for the new relapse.The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.
The TCS score was calculated only for the time point after treatment of relapse. It was a sum of questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. Scores range from 0 to 30 units, with higher scores representing greater improvement/better functioning.
measure: ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores)
time frame: baseline visit & follow-up after treatment
description: Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse.
The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability.
PCS was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; Higher scores indicating better functioning/greater improvement. The PCS scores were on a scale of 0 to 20 units.
measure: MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score
time frame: baseline visit & follow-up after treatment
description: The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS.
The physical impact of MS was compared between pre and post phase using paired t-tests. Each question is answered with points ranging from 1 to 5. Higher score indicates worse outcome. The total MSIS physical score ranges from 20 to 100 points with lower points indicating better impact.
measure: MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score.
time frame: baseline visit & follow-up after treatment
description: The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS and 9 questions assess the psychological impact of MS.
The psychological impact of MS was compared between pre and post phase using paired t-tests.
The psychological impact of MS was compared between pre and post phase using paired t-tests.
The score was on a scale of 9 to 45 points for MSIS psychological score.
Higher score indicate worse outcome.
measure: EDSS (Expanded Disability Status Scale) Scores.
time frame: baseline and at follow-up
description: This scaling score is obtained by performing a neurologic exam with specific attention to eight different neurologic functional systems: visual, pyramidal, cerebellar, bowel and bladder, cerebral, brainstem, sensory and other (10). The score is rated from zero (normal neurologic examination) to ten (death due to MS). This is the standard neurologic disability scale used in clinical trials for the evaluation of disability in patients with MS.
These scores were compared between pre and post phase using paired t-tests.
measure: SAGE (Self-administered Gerocognitive Exam) Scores
time frame: baseline and follow-up
description: The Self-Administered Gerocognitive Exam (SAGE) is designed to detect early signs of cognitive, memory or thinking impairments. It evaluates your thinking abilities and helps physicians to know how well your brain is working.
It consists of 12 questions which are scored at different scales. The final SAGE score is calculated as a sum of these 12 questions and it ranges from 0 to 22.
Higher score indicates better outcome.
measure: GASE Scale Questionnaire (Generic Assessment of Side Effects)
time frame: 1 week
description: Patients who reported a history of poor corticosteroid tolerability will be placed on Acthar and GASE scale will be given to assess tolerability to Acthar.
We listed the number of times a symptom was reported and was attributable to the ACTHAR treatment
arm group label: Single arm
arm group type: Experimental
description: Acthar 80 units subcutaneously for five consecutive days.
intervention type: Drug
intervention name: Acthar
description: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.
arm group label: Single arm
other name: repository corticotropin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Aaron L Boster, MD
role: Principal Investigator
affiliation: OhioHealth
facility: 
country: United States
citation: Fox RJ, Bethoux F, Goldman MD, Cohen JA. Multiple sclerosis: advances in understanding, diagnosing, and treating the underlying disease. Cleve Clin J Med. 2006 Jan;73(1):91-102. doi: 10.3949/ccjm.73.1.91.
PMID: 16444920
citation: Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907-11. doi: 10.1212/wnl.46.4.907.
PMID: 8780061
citation: Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.
PMID: 11006371
citation: O'Brien JA, Ward AJ, Patrick AR, Caro J. Cost of managing an episode of relapse in multiple sclerosis in the United States. BMC Health Serv Res. 2003 Sep 2;3(1):17. doi: 10.1186/1472-6963-3-17.
PMID: 12952552
citation: Barnes D, Hughes RA, Morris RW, Wade-Jones O, Brown P, Britton T, Francis DA, Perkin GD, Rudge P, Swash M, Katifi H, Farmer S, Frankel J. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997 Mar 29;349(9056):902-6. doi: 10.1016/s0140-6736(96)06453-7.
PMID: 9093250
citation: Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology. 2004 Sep 28;63(6):1079-80. doi: 10.1212/01.wnl.0000138572.82125.f5.
PMID: 15452302
citation: La Mantia L, Eoli M, Milanese C, Salmaggi A, Dufour A, Torri V. Double-blind trial of dexamethasone versus methylprednisolone in multiple sclerosis acute relapses. Eur Neurol. 1994;34(4):199-203. doi: 10.1159/000117038.
PMID: 7915989
citation: Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2012 Dec 12;12:CD006921. doi: 10.1002/14651858.CD006921.pub3.
PMID: 23235634
citation: Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.
PMID: 21387374
citation: Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.
PMID: 6685237
citation: Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure. Brain. 2001 May;124(Pt 5):962-73. doi: 10.1093/brain/124.5.962.
PMID: 11335698
citation: Perrin Ross A, Williamson A, Smrtka J, Flemming Tracy T, Saunders C, Easterling C, Niewoehner J, Mutschler N. Assessing relapse in multiple sclerosis questionnaire: results of a pilot study. Mult Scler Int. 2013;2013:470476. doi: 10.1155/2013/470476. Epub 2013 May 26.
PMID: 23766909
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis
mesh term: Adrenocorticotropic Hormone
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 