<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/NCT03268603</url>
  </required_header>
  <id_info>
    <org_study_id>15-008008</org_study_id>
    <nct_id>NCT03268603</nct_id>
  </id_info>
  <brief_title>Intrathecal Autologous Adipose-derived Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis (ALS)</brief_title>
  <official_title>A Phase II Study of Intrathecal Autologous Adipose-derived Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>State of Minnesota Regenerative Medicine Minnesota</agency>
      <agency_class>Other</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and efficacy of intrathecal treatment&#xD;
      delivered to the cerebrospinal fluid (CSF) of mesenchymal stem cells in ALS patients every 3&#xD;
      months for a total of 4 injections over 12 months.&#xD;
&#xD;
      Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown into a number of&#xD;
      different kinds of cells. In this study, MSCs will be taken from the subject's body fat and&#xD;
      grown. CSF is the fluid surrounding the spine.&#xD;
&#xD;
      The use of mesenchymal stem cells is considered investigational, which means it has not been&#xD;
      approved by the Food and Drug Administration (FDA) for routine clinical use. However, the FDA&#xD;
      has allowed the use of mesenchymal stem cells in this research study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Goal of the Proposed Study is to perform an open label, 60 subject, Phase II multi-site&#xD;
      clinical trial to investigate the safety and efficacy of intrathecal treatment of aaMSCs in&#xD;
      ALS. Patients will be treated with 10-100 million aaMSCs every 3 months for a total of 4&#xD;
      intrathecal injections over 12 months. Reduced dose treatments will be allowed based on&#xD;
      specific adverse events. Multiple biomarkers will be tracked throughout the clinical trial&#xD;
      and correlated with response to treatment. This study was initially performed at Mayo Clinic&#xD;
      in Rochester and subsequently expanded to the two other Mayo Clinic sites in Arizona and&#xD;
      Florida. All biopsies and stem cell injections take place at Mayo Clinic Rochester,&#xD;
      regardless of where the subject initially enrolls into the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 10, 2017</start_date>
  <completion_date type="Anticipated">November 2023</completion_date>
  <primary_completion_date type="Anticipated">November 2023</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 Adverse Events</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>Number of adverse events will be recorded from the time of enrollment until the end of the follow-up period or, in the case of early withdrawal, to the time of study withdrawal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in slope of ALS Functional Rating Scale - Revised (ALSFRS-R)</measure>
    <time_frame>baseline, approximately 1 year</time_frame>
    <description>The ALSFRS-R includes 12 questions. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>ALS</condition>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Mesenchymal Stromal Cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous Adipose-derived Mesenchymal Stromal Cells (aaMSCs) will be administered intrathecally at a single dose in a volume of 5-10 mL, all patients will receive 5 x 10^7 intrathecal aaMSCs at the first injection (Visit 4). Subsequent doses may be reduced to 1 x 10^7 or increased to 1 x 10^8, based on Dose Modification Rules.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Autologous Adipose-derived Mesenchymal Stromal Cells</intervention_name>
    <description>The investigational product consists of autologous adipose-derived Mesenchymal Stromal Cells (MSCs), suspended in 5-10 mL Lactated Ringer's. The MSC are provided in a sterile syringe labelled with appropriate patient and product identifiers ready for intrathecal injection.</description>
    <arm_group_label>Mesenchymal Stromal Cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients will have ALS diagnosed as possible, laboratory-supported probable,&#xD;
             probable, or definite as defined by the World Federation of Neurology criteria for the&#xD;
             diagnosis of ALS.&#xD;
&#xD;
          -  Examination and neurophysiological testing confirm a pure motor syndrome compatible&#xD;
             with the diagnosis of ALS. All other possible causes of weakness have been excluded by&#xD;
             extensive investigations.&#xD;
&#xD;
          -  Age greater than 18 years, if female, must be post-menopausal, had a hysterectomy, or&#xD;
             agree to two forms of birth control.&#xD;
&#xD;
          -  Permanent resident or citizen of the United States.&#xD;
&#xD;
          -  Geographic accessibility to the study site and willingness and ability to comply with&#xD;
             follow-up.&#xD;
&#xD;
          -  History of a chronic onset of a progressive motor weakness of less than two years&#xD;
             duration.&#xD;
&#xD;
          -  Subjects must be taking a stable dose of riluzole for at least 30 days prior to&#xD;
             enrolment or not be on riluzole, and not have been on it for at least 30 days prior to&#xD;
             enrolment (riluzole-naïve subjects are permitted in the study).&#xD;
&#xD;
          -  Able to comply with protocol requirements, including MRI testing.&#xD;
&#xD;
          -  Can provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of Radicava® (edaravone) within 30 days of screening or intent to use Radicava® at&#xD;
             any time during the course of the study including the follow up period.&#xD;
&#xD;
          -  Any clinically significant medical condition (e.g., within six months of baseline, had&#xD;
             myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the&#xD;
             opinion of the investigator, would compromise the safety of patient.&#xD;
&#xD;
          -  Pulmonary Slow Vital Capacity (SVC) less than 65% of predicted for age, gender, and&#xD;
             body type.&#xD;
&#xD;
          -  Autoimmunity, including Crohn's disease or rheumatoid arthritis&#xD;
&#xD;
          -  Current use of immunosuppressant medication or use of such medication within 4 weeks&#xD;
             of Screening visit (Visit 1).&#xD;
&#xD;
          -  Malignancy 5 years prior to enrollment, including melanoma,with the exception of&#xD;
             localized skin cancers (with no evidence of metastasis, significant invasion, or&#xD;
             re-occurrence within three years of baseline).&#xD;
&#xD;
          -  Active systemic or local infection near the lumbar puncture site.&#xD;
&#xD;
          -  Inability to lie flat for the duration of intrathecal cell transplantation, or&#xD;
             inability to tolerate study procedures for any other reason.&#xD;
&#xD;
          -  Other active systemic disease as defined by laboratory abnormalities delineated in&#xD;
             Appendix IV.&#xD;
&#xD;
          -  Use of herbal medications, nutritional supplements or other unapproved drugs or&#xD;
             investigational medicinal products being used or studied for the treatment of ALS.&#xD;
&#xD;
          -  Unwilling to forgo initiating the use of any new supplements during participation in&#xD;
             the study.&#xD;
&#xD;
          -  Enrolled in an investigational drug trial within 30 days of baseline visit&#xD;
&#xD;
          -  Prior stem cell therapy for a neurological disease&#xD;
&#xD;
          -  Kokmen Short Test of Mental Status score &lt;32&#xD;
&#xD;
          -  Presence of a tracheostomy&#xD;
&#xD;
          -  Ventilator dependent&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
             contraception&#xD;
&#xD;
          -  Chronic low back pain requiring invasive procedures (i.e. epidural injections or&#xD;
             lumbar spine surgery)&#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>Nathan P Staff, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anthony J Windebank, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>February 2, 2023</last_update_submitted>
  <last_update_submitted_qc>February 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Nathan P. Staff</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03268603
org study id: 15-008008
nct id: NCT03268603
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the safety and efficacy of intrathecal treatment
      delivered to the cerebrospinal fluid (CSF) of mesenchymal stem cells in ALS patients every 3
      months for a total of 4 injections over 12 months.

      Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown into a number of
      different kinds of cells. In this study, MSCs will be taken from the subject's body fat and
      grown. CSF is the fluid surrounding the spine.

      The use of mesenchymal stem cells is considered investigational, which means it has not been
      approved by the Food and Drug Administration (FDA) for routine clinical use. However, the FDA
      has allowed the use of mesenchymal stem cells in this research study.
The Goal of the Proposed Study is to perform an open label, 60 subject, Phase II multi-site
      clinical trial to investigate the safety and efficacy of intrathecal treatment of aaMSCs in
      ALS. Patients will be treated with 10-100 million aaMSCs every 3 months for a total of 4
      intrathecal injections over 12 months. Reduced dose treatments will be allowed based on
      specific adverse events. Multiple biomarkers will be tracked throughout the clinical trial
      and correlated with response to treatment. This study was initially performed at Mayo Clinic
      in Rochester and subsequently expanded to the two other Mayo Clinic sites in Arizona and
      Florida. All biopsies and stem cell injections take place at Mayo Clinic Rochester,
      regardless of where the subject initially enrolls into the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events
time frame: approximately 2 years
description: Number of adverse events will be recorded from the time of enrollment until the end of the follow-up period or, in the case of early withdrawal, to the time of study withdrawal.
measure: Change in slope of ALS Functional Rating Scale - Revised (ALSFRS-R)
time frame: baseline, approximately 1 year
description: The ALSFRS-R includes 12 questions. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.
arm group label: Mesenchymal Stromal Cells
arm group type: Experimental
description: Autologous Adipose-derived Mesenchymal Stromal Cells (aaMSCs) will be administered intrathecally at a single dose in a volume of 5-10 mL, all patients will receive 5 x 10^7 intrathecal aaMSCs at the first injection (Visit 4). Subsequent doses may be reduced to 1 x 10^7 or increased to 1 x 10^8, based on Dose Modification Rules.
intervention type: Drug
intervention name: Autologous Adipose-derived Mesenchymal Stromal Cells
description: The investigational product consists of autologous adipose-derived Mesenchymal Stromal Cells (MSCs), suspended in 5-10 mL Lactated Ringer's. The MSC are provided in a sterile syringe labelled with appropriate patient and product identifiers ready for intrathecal injection.
arm group label: Mesenchymal Stromal Cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nathan P Staff, MD, PhD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Anthony J Windebank, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
facility: 
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Nathan P. Staff
investigator title: Professor of Neurology
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
sharing ipd: No