<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/NCT03749096</url>
  </required_header>
  <id_info>
    <org_study_id>18-007041</org_study_id>
    <nct_id>NCT03749096</nct_id>
  </id_info>
  <brief_title>Randomized Placebo Controlled Trial of IVIg in Glycine Receptor Antibody Positive Stiff-person Syndrome</brief_title>
  <official_title>IVIg in Glycine Receptor Antibody Positive Stiff-person Syndrome (SPS) Spectrum Disorders.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Grifols Biologicals, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized double-blind controlled trial of intravenous immunoglobulin (IVIg) for&#xD;
      glycine receptor antibody positive (GlyRα1) antibody Stiff Person Syndrome (SPS) spectrum&#xD;
      disorders. Adult patients will be enrolled over the course of 36 months. Study duration per&#xD;
      patient will be 11 weeks. Total study duration will be 39 months. All treatment and study&#xD;
      visits will occur at Mayo Clinic in Rochester, MN.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to determine whether intravenous immunoglobulin (IVIG) treatment&#xD;
      reduces stiffness and spasms in patients with SPS spectrum disorders compared to patients who&#xD;
      do not receive any treatment. In this study, investigators want to compare the effects, good&#xD;
      and/or bad, of IVIG with placebo on participants with SPS to find out which is better. This&#xD;
      is a &quot;randomized, double-blind&quot; study. Which treatment participants will receive is randomly&#xD;
      determined. Participants have an equal chance of receiving IVIG or the placebo.&#xD;
&#xD;
      SPS spectrum cohort will include any from the SPS spectrum patient (stiff-limbs, stiff-trunk,&#xD;
      stiff-limbs and trunk, and PERM). Study visits will be considered part of clinical care and&#xD;
      will occur at: enrollment (will coincide with screening visit), and 11 weeks. IVIg/placebo&#xD;
      (saline) treatments will be administered on 2 consecutive days in week 1, week 5, week 9 in&#xD;
      all patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Recruitment did not meet sponsors timeline&#xD;
  </why_stopped>
  <start_date type="Actual">December 7, 2018</start_date>
  <completion_date type="Actual">April 26, 2019</completion_date>
  <primary_completion_date type="Actual">April 26, 2019</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Randomized double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Distribution-of-stiffness index</measure>
    <time_frame>Screen, Week 11</time_frame>
    <description>Scores on this index range from 0 to 6 and reflect the extent of stiffness. with One point being given for stiffness in each of the following areas: lower trunk, upper trunk, legs, arms, face, and abdomen. Lower scores indicate less stiffness.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Heightened-sensitivity scale</measure>
    <time_frame>Screen, Week 11</time_frame>
    <description>Scores range from 1 to 7 based on response; one point being given for each source of or type of spasm, as follows: unexpected noises, visual stimuli, somatosensory stimuli, voluntary activities, emotional upset or stress, no specific stimuli, and nocturnal spasms. Lower scores indicate less frequent spasms.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Stiff-Person Syndrome</condition>
  <arm_group>
    <arm_group_label>Intravenous immunoglobulin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IVIg dose will be 2g/kg ideal body weight every 4 weeks (in 2 divided doses on consecutive days) for 12 weeks (3 cycles total).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous Immunoglobulins, Human</intervention_name>
    <description>Immunoglobulins are fractionated blood products made from pooled human plasma.</description>
    <arm_group_label>Intravenous immunoglobulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Normal Saline</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Patient must be 18 years of age or older&#xD;
&#xD;
          -  Must have symptoms of SPS for less than 3 years&#xD;
&#xD;
          -  If taking corticosteroids, the patients must be on a stabile dose for 30 days prior to&#xD;
             enrolment&#xD;
&#xD;
          -  Patients will have a diagnosis of SPS spectrum disorder based on both of clinical and&#xD;
             serological status&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Patients on immune suppressants initiated/dose increased in the prior 6 months&#xD;
&#xD;
          -  History of thrombotic episodes within the 2 years prior to enrollment&#xD;
&#xD;
          -  Known allergic or other severe reactions to blood products including intolerability to&#xD;
             previous IVIG&#xD;
&#xD;
          -  Previous adequate trial of IVIG as determined by the Principal Investigator&#xD;
&#xD;
          -  IgA deficiency&#xD;
&#xD;
          -  Reproductive status:&#xD;
&#xD;
               -  Women who are pregnant, breastfeeding&#xD;
&#xD;
               -  Women and men of childbearing potential who are unwilling or unable to use an&#xD;
                  acceptable method of birth control to avoid pregnancy for the entire study&#xD;
                  period, as evaluated by the investigator.&#xD;
&#xD;
          -  Any surgical procedure within 4 weeks prior to baseline.&#xD;
&#xD;
          -  Evidence of serious uncontrolled concomitant diseases that may preclude patient&#xD;
             participation; Other nervous system disease, cardiovascular disease,&#xD;
             hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine&#xD;
             disease, renal/urologic disease, digestive system disease, congenital or acquired&#xD;
             severe immunodeficiency&#xD;
&#xD;
          -  Known active infection within 4 weeks prior to baseline.&#xD;
&#xD;
          -  Evidence of chronic active hepatitis B or C.&#xD;
&#xD;
          -  Active ischemic heart disease in the past year prior to baseline.&#xD;
&#xD;
          -  Patients should not have severe renal or hepatic disease&#xD;
&#xD;
          -  Severe hypertension&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew McKeon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>June 11, 2019</last_update_submitted>
  <last_update_submitted_qc>June 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Andrew McKeon</investigator_full_name>
    <investigator_title>Prinicple Investigator</investigator_title>
  </responsible_party>
  <keyword>IVIG</keyword>
  <keyword>stiff-person syndrome</keyword>
  <keyword>SPS</keyword>
  <keyword>glycine receptor antibody</keyword>
  <keyword>intravenous immunoglobulin</keyword>
  <keyword>GlyRα1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stiff-Person Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>gamma-Globulins</mesh_term>
    <mesh_term>Rho(D) Immune Globulin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03749096
org study id: 18-007041
nct id: NCT03749096
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a randomized double-blind controlled trial of intravenous immunoglobulin (IVIg) for
      glycine receptor antibody positive (GlyRα1) antibody Stiff Person Syndrome (SPS) spectrum
      disorders. Adult patients will be enrolled over the course of 36 months. Study duration per
      patient will be 11 weeks. Total study duration will be 39 months. All treatment and study
      visits will occur at Mayo Clinic in Rochester, MN.
The purpose of this study is to determine whether intravenous immunoglobulin (IVIG) treatment
      reduces stiffness and spasms in patients with SPS spectrum disorders compared to patients who
      do not receive any treatment. In this study, investigators want to compare the effects, good
      and/or bad, of IVIG with placebo on participants with SPS to find out which is better. This
      is a "randomized, double-blind" study. Which treatment participants will receive is randomly
      determined. Participants have an equal chance of receiving IVIG or the placebo.

      SPS spectrum cohort will include any from the SPS spectrum patient (stiff-limbs, stiff-trunk,
      stiff-limbs and trunk, and PERM). Study visits will be considered part of clinical care and
      will occur at: enrollment (will coincide with screening visit), and 11 weeks. IVIg/placebo
      (saline) treatments will be administered on 2 consecutive days in week 1, week 5, week 9 in
      all patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Randomized double-blind
measure: Change in Distribution-of-stiffness index
time frame: Screen, Week 11
description: Scores on this index range from 0 to 6 and reflect the extent of stiffness. with One point being given for stiffness in each of the following areas: lower trunk, upper trunk, legs, arms, face, and abdomen. Lower scores indicate less stiffness.
measure: Change in Heightened-sensitivity scale
time frame: Screen, Week 11
description: Scores range from 1 to 7 based on response; one point being given for each source of or type of spasm, as follows: unexpected noises, visual stimuli, somatosensory stimuli, voluntary activities, emotional upset or stress, no specific stimuli, and nocturnal spasms. Lower scores indicate less frequent spasms.
arm group label: Intravenous immunoglobulin
arm group type: Active Comparator
description: IVIg dose will be 2g/kg ideal body weight every 4 weeks (in 2 divided doses on consecutive days) for 12 weeks (3 cycles total).
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Intravenous Immunoglobulins, Human
description: Immunoglobulins are fractionated blood products made from pooled human plasma.
arm group label: Intravenous immunoglobulin
intervention type: Drug
intervention name: Placebos
description: Normal Saline
arm group label: Placebo
other name: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew McKeon, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Andrew McKeon
investigator title: Prinicple Investigator
mesh term: Stiff-Person Syndrome
mesh term: Syndrome
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
mesh term: Antibodies
mesh term: gamma-Globulins
mesh term: Rho(D) Immune Globulin