<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/NCT01722682</url>
  </required_header>
  <id_info>
    <org_study_id>IsletBOM2</org_study_id>
    <nct_id>NCT01722682</nct_id>
  </id_info>
  <brief_title>Bone Marrow vs Liver as Site for Islet Transplantation</brief_title>
  <acronym>IsletBOM2</acronym>
  <official_title>Bone Marrow vs Liver as Site for Islet Transplantation in Patients With Type 1 Diabetes: Pilot Study to Evaluate Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ospedale San Raffaele</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to evaluate safety and efficacy of bone marrow (BM) as site for&#xD;
      pancreatic islet transplantationin humans. Our hypothesis is that BM represents a better site&#xD;
      than liver (currently the location of choice for this procedure) thanks to its potential&#xD;
      capacity to favor islet engraftment. To address our hypothesis we propose herein a randomized&#xD;
      phase II trial to compare BM and liver as sites for islet transplantation in T1D patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a phase II, single center, open label, pilot study. We will recruit 12 patients&#xD;
      with T1D to be randomly (1:1) assigned to receive islet either into the liver through the&#xD;
      portal venous circulation (standard procedure; arm A, n=6) or directly into the BM at the&#xD;
      level of the iliac crest (arm B, n=6). Patients will be selected from those eligible for&#xD;
      islet Tx based on local practice and guidelines.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">September 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin secretion under stimulation</measure>
    <time_frame>month 12 post-Tx</time_frame>
    <description>basal and -10 to 120 min time course of glucose, C-pep levels and insulin derived from the mixed meal tolerance test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of Adverse Events (AE) and Serious Adverse Events (SAE)</measure>
    <time_frame>throughout the study up to 1 year after first transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin requirement</measure>
    <time_frame>month 1, 3, 6, 9, 12 post- transplant</time_frame>
    <description>Change in average daily insulin requirements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Islet function</measure>
    <time_frame>month 1, 3, 6, 9, 12 post-Tx</time_frame>
    <description>change in HbA1c, Transplant Estimated Function (TEF) and fasting C-peptide levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>A: intraportal islet infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will received islet into the liver through the portal venous circulation (standard procedure)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: intra BM islet infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will received an intra BM islet infusion at the level of the iliac crest. The direct intra BM administration will be performed following the same procedures that our institution utilizes for administration of cord-blood cells in patients with acute leukemia (Lancet Oncol. 2008;9:831). The procedure is easy and reproducible: a standard needle for BM aspiration is inserted in the iliac crest and cells are gently infused.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human pancreatic islet transplantation</intervention_name>
    <arm_group_label>A: intraportal islet infusion</arm_group_label>
    <arm_group_label>B: intra BM islet infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diabetic patients eligible for pancreatic islet transplantation based on local&#xD;
             accepted practice and guidelines. This includes at least: a)clinical history&#xD;
             compatible with T1D with insulin-dependence for &gt;5 years; b) undetectable stimulated&#xD;
             (arginine or MMTT) C-peptide levels (&lt;0.3 ng/mL) in the 12 months before transplant&#xD;
             c)presence of severe hypoglycaemic events&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  presence of hematologic disease&#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>Lorenzo Piemonti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale San Raffaele</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>http://www.hsr.it/ricerca/divisioni-centri-istituti-e-programmi-di-ricerca/islet-trasplantation-program-itp/</url>
    <description>Related Info</description>
  </link>
  <results_reference>
    <citation>Maffi P, Nano R, Monti P, Melzi R, Sordi V, Mercalli A, Pellegrini S, Ponzoni M, Peccatori J, Messina C, Nocco A, Cardillo M, Scavini M, Magistretti P, Doglioni C, Ciceri F, Bloem SJ, Roep BO, Secchi A, Piemonti L. Islet Allotransplantation in the Bone Marrow of Patients With Type 1 Diabetes: A Pilot Randomized Trial. Transplantation. 2019 Apr;103(4):839-851. doi: 10.1097/TP.0000000000002416.</citation>
    <PMID>30130323</PMID>
  </results_reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>November 2, 2020</last_update_submitted>
  <last_update_submitted_qc>November 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale San Raffaele</investigator_affiliation>
    <investigator_full_name>Piemonti Lorenzo</investigator_full_name>
    <investigator_title>Head of Beta Cell Biology Unit, CO-Director Human Islet Transplantation Program (ITP)</investigator_title>
  </responsible_party>
  <keyword>Diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_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/NCT01722682
org study id: IsletBOM2
nct id: NCT01722682
lead sponsor: 
collaborator: 
has dmc: Yes
The goal of this study is to evaluate safety and efficacy of bone marrow (BM) as site for
      pancreatic islet transplantationin humans. Our hypothesis is that BM represents a better site
      than liver (currently the location of choice for this procedure) thanks to its potential
      capacity to favor islet engraftment. To address our hypothesis we propose herein a randomized
      phase II trial to compare BM and liver as sites for islet transplantation in T1D patients.
The study is a phase II, single center, open label, pilot study. We will recruit 12 patients
      with T1D to be randomly (1:1) assigned to receive islet either into the liver through the
      portal venous circulation (standard procedure; arm A, n=6) or directly into the BM at the
      level of the iliac crest (arm B, n=6). Patients will be selected from those eligible for
      islet Tx based on local practice and guidelines.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Insulin secretion under stimulation
time frame: month 12 post-Tx
description: basal and -10 to 120 min time course of glucose, C-pep levels and insulin derived from the mixed meal tolerance test
measure: Incidence and severity of Adverse Events (AE) and Serious Adverse Events (SAE)
time frame: throughout the study up to 1 year after first transplant
measure: Insulin requirement
time frame: month 1, 3, 6, 9, 12 post- transplant
description: Change in average daily insulin requirements
measure: Islet function
time frame: month 1, 3, 6, 9, 12 post-Tx
description: change in HbA1c, Transplant Estimated Function (TEF) and fasting C-peptide levels
arm group label: A: intraportal islet infusion
arm group type: Active Comparator
description: Patients will received islet into the liver through the portal venous circulation (standard procedure)
arm group label: B: intra BM islet infusion
arm group type: Experimental
description: Patients will received an intra BM islet infusion at the level of the iliac crest. The direct intra BM administration will be performed following the same procedures that our institution utilizes for administration of cord-blood cells in patients with acute leukemia (Lancet Oncol. 2008;9:831). The procedure is easy and reproducible: a standard needle for BM aspiration is inserted in the iliac crest and cells are gently infused.
intervention type: Biological
intervention name: Human pancreatic islet transplantation
arm group label: A: intraportal islet infusion
arm group label: B: intra BM islet infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lorenzo Piemonti, MD
role: Principal Investigator
affiliation: Ospedale San Raffaele
facility: 
country: Italy
url: http://www.hsr.it/ricerca/divisioni-centri-istituti-e-programmi-di-ricerca/islet-trasplantation-program-itp/
description: Related Info
citation: Maffi P, Nano R, Monti P, Melzi R, Sordi V, Mercalli A, Pellegrini S, Ponzoni M, Peccatori J, Messina C, Nocco A, Cardillo M, Scavini M, Magistretti P, Doglioni C, Ciceri F, Bloem SJ, Roep BO, Secchi A, Piemonti L. Islet Allotransplantation in the Bone Marrow of Patients With Type 1 Diabetes: A Pilot Randomized Trial. Transplantation. 2019 Apr;103(4):839-851. doi: 10.1097/TP.0000000000002416.
PMID: 30130323
responsible party type: Principal Investigator
investigator affiliation: Ospedale San Raffaele
investigator full name: Piemonti Lorenzo
investigator title: Head of Beta Cell Biology Unit, CO-Director Human Islet Transplantation Program (ITP)
mesh term: Diabetes Mellitus, Type 1