<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/NCT01719159</url>
  </required_header>
  <id_info>
    <org_study_id>ITT-PMS</org_study_id>
    <nct_id>NCT01719159</nct_id>
  </id_info>
  <brief_title>Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis</brief_title>
  <acronym>ITT-PMS</acronym>
  <official_title>Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anders Svenningsson</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Västerbotten County Council, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Umeå University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a is a small scale open phase two interventional study to assess long-term&#xD;
      stabilising effects of on neurological symptoms by regular intrathecal administered&#xD;
      monoclonal antibodies in progressive multiple sclerosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is presently no efficient therapy available in progressive MS, especially if there is&#xD;
      no clear evidence of active inflammatory lesions or exacerbations as part of the disease.&#xD;
      There are, however, evidence that some treatment protocols using cytotoxic drugs may to some&#xD;
      extent slow down the progressive course. One specific feature of long-standing MS is that&#xD;
      inflammatory cells accumulate in the central nervous system(CNS) compartment in the&#xD;
      subarachnoid and perivascular spaces and may therefore be hard to reach via standard drug&#xD;
      delivery through systemic administration. Administration of substances via the Intrathecal&#xD;
      (IT) route, however, have shown to efficiently distribute in the subarachnoid spaces and may&#xD;
      therefore be an attractive route of drug delivery&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2009</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>One year after completed treatment</time_frame>
    <description>Feasibility of IT administered monoclonal antibodies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stabilisation of the neurological deterioration</measure>
    <time_frame>At 3,6,9,12 month after completed treatment</time_frame>
    <description>Questionaires regarding MS quality of life, symptom inventory and fatigue will be used.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Immunological markers in blood</measure>
    <time_frame>At 3,6,9,12 month after treatment</time_frame>
    <description>I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset</description>
  </other_outcome>
  <other_outcome>
    <measure>Immunological markers in cerebrospinal fluid (CSF)</measure>
    <time_frame>At 3, 6, 9 12 month after treatment</time_frame>
    <description>I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rituximab, 25 mg, is administrated intrathecal three times one week apart</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.</description>
    <arm_group_label>Rituximab</arm_group_label>
    <other_name>Mabthera</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Between the age of 18 and 65 years of age (nonfertile women or fertile women with&#xD;
             effective contraceptive methods)&#xD;
&#xD;
          -  Progressive MS since at least three years&#xD;
&#xD;
          -  Some kind of documented progression of neurological symptoms during the previous two&#xD;
             years.&#xD;
&#xD;
          -  Expanded Disability Status Scale (EDSS) 4,0 - 7.0 (inclusive) (basically spared arm&#xD;
             functions)&#xD;
&#xD;
          -  Conventional therapy not indicated, contraindicated or failed&#xD;
&#xD;
          -  Judged as compliant with the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Eligible for any of the conventional MS therapies&#xD;
&#xD;
          -  Relapsing remitting multiple sclerosis (RRMS)&#xD;
&#xD;
          -  Bleeding diathesis or medication contraindicating neurosurgical procedures or lumbar&#xD;
             puncture&#xD;
&#xD;
          -  Cognitive defect making informed consent unreliable&#xD;
&#xD;
          -  Any medical condition contraindicating minor surgical procedures, as judged by&#xD;
             anaesthesiologist&#xD;
&#xD;
          -  Severe, uncontrolled heart disease&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Patients having contraindication for or otherwise not compliant with MRI&#xD;
             investigations&#xD;
&#xD;
          -  Documented vulnerability to infections&#xD;
&#xD;
          -  Simultaneous treatment with other immunosuppressive drugs&#xD;
&#xD;
          -  Documented allergy or intolerance to Rituximab&#xD;
&#xD;
          -  Severe psychiatric condition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anders Svenningsson, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Umea university</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of neurology, Umeå University Hospital</name>
      <address>
        <city>Umeå</city>
        <zip>901 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dept of neurology, Uppsala University Hospital</name>
      <address>
        <city>Uppsala</city>
        <zip>SE-751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>November 18, 2016</last_update_submitted>
  <last_update_submitted_qc>November 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Umeå University</investigator_affiliation>
    <investigator_full_name>Anders Svenningsson</investigator_full_name>
    <investigator_title>MD, PhD, Assoc Prof</investigator_title>
  </responsible_party>
  <keyword>Progressive multiple sclerosis</keyword>
  <keyword>Monoclonal antibodies</keyword>
  <keyword>Mabthera</keyword>
  <keyword>Intrathecal treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>IPD will be shared upon request from the researcher or scientific journals</ipd_description>
  </patient_data>
  <!-- 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/NCT01719159
org study id: ITT-PMS
nct id: NCT01719159
lead sponsor: 
collaborator: 
has dmc: No
This is a is a small scale open phase two interventional study to assess long-term
      stabilising effects of on neurological symptoms by regular intrathecal administered
      monoclonal antibodies in progressive multiple sclerosis.
There is presently no efficient therapy available in progressive MS, especially if there is
      no clear evidence of active inflammatory lesions or exacerbations as part of the disease.
      There are, however, evidence that some treatment protocols using cytotoxic drugs may to some
      extent slow down the progressive course. One specific feature of long-standing MS is that
      inflammatory cells accumulate in the central nervous system(CNS) compartment in the
      subarachnoid and perivascular spaces and may therefore be hard to reach via standard drug
      delivery through systemic administration. Administration of substances via the Intrathecal
      (IT) route, however, have shown to efficiently distribute in the subarachnoid spaces and may
      therefore be an attractive route of drug delivery
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events
time frame: One year after completed treatment
description: Feasibility of IT administered monoclonal antibodies
measure: Stabilisation of the neurological deterioration
time frame: At 3,6,9,12 month after completed treatment
description: Questionaires regarding MS quality of life, symptom inventory and fatigue will be used.
measure: Immunological markers in blood
time frame: At 3,6,9,12 month after treatment
description: I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset
measure: Immunological markers in cerebrospinal fluid (CSF)
time frame: At 3, 6, 9 12 month after treatment
description: I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset
arm group label: Rituximab
arm group type: Experimental
description: Rituximab, 25 mg, is administrated intrathecal three times one week apart
intervention type: Drug
intervention name: Rituximab
description: 25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.
arm group label: Rituximab
other name: Mabthera
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Anders Svenningsson, MD, PhD
role: Principal Investigator
affiliation: Umea university
facility: 
facility: 
country: Sweden
responsible party type: Sponsor-Investigator
investigator affiliation: Umeå University
investigator full name: Anders Svenningsson
investigator title: MD, PhD, Assoc Prof
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
mesh term: Rituximab
sharing ipd: Undecided
ipd description: IPD will be shared upon request from the researcher or scientific journals