<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/NCT02213003</url>
  </required_header>
  <id_info>
    <org_study_id>20140144</org_study_id>
    <nct_id>NCT02213003</nct_id>
  </id_info>
  <brief_title>Allogeneic Islet Cells Transplanted Onto the Omentum</brief_title>
  <official_title>Allogeneic Islet Cells Transplanted Onto the Omentum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rodolfo Alejandro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Juvenile Diabetes Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Diabetes Research Institute Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Current islet transplantation into the portal vein of the liver has shown the unique ability&#xD;
      of islets to stabilize blood glucose levels and prevent severe hypoglycemia in a selected&#xD;
      group of subjects with Type 1 diabetes. The main limitations of islet transplantation are the&#xD;
      need for systemic immunosuppression to maintain function and the loss of islet function over&#xD;
      time. Additionally, many studies have demonstrated that the current site of transplantation&#xD;
      in the liver is not an ideal site due to several factors. These factors include (1)&#xD;
      significant liver inflammation following islet infusion; (2) potential for life-threatening&#xD;
      procedure-related complications such as bleeding and thrombosis; (3) high levels of&#xD;
      immunosuppressive drugs and GI toxins in the liver contributing to islet toxicity; (4) the&#xD;
      inability to retrieve islets after infusion; and (5) development of graft dysfunction in a&#xD;
      number of recipients of intrahepatic allogeneic and autologous islets. The implantation of&#xD;
      islets into the omentum will allow adequate engraftment of islets onto the omentum and will&#xD;
      lead to comparable or superior functional and clinical outcomes than in the traditional&#xD;
      intrahepatic site.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Islet transplantation will be performed in subjects with unstable Type 1 diabetes mellitus&#xD;
      under permanent immunosuppression. Islets are re-suspended in autologous plasma and&#xD;
      distributed on the omental surface by a minimal invasive approach. Cell adherence is achieved&#xD;
      by addition of clinical-grade recombinant human thrombin that reacts with plasma to create a&#xD;
      biocompatible, degradable gel containing the islet graft. The primary efficacy endpoint is&#xD;
      the proportion of subjects with HbA1c ≤6.5% at 1 year AND free of severe hypoglycemic events&#xD;
      from Day 28 to Day 365, inclusive, after the islet transplant. The primary safety endpoint is&#xD;
      to demonstrate patient safety throughout all stages of the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">May 2026</completion_date>
  <primary_completion_date type="Anticipated">May 2025</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>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>A1c &lt;/= 6.5% and no severe hypoglycemia</measure>
    <time_frame>1 year</time_frame>
    <description>composite outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>procedural complications</measure>
    <time_frame>1 year</time_frame>
    <description>safety</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">6</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <condition>Hypoglycemia</condition>
  <condition>Hypoglycemia Unawareness</condition>
  <arm_group>
    <arm_group_label>Islet transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transplantation of at least 5000 islet equivalents/kg of body weight onto the omentum.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Islet transplantation</intervention_name>
    <description>Transplantation of at least 5000 islet equivalents/kg of body weight onto the Omentum.</description>
    <arm_group_label>Islet transplantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients age 18 to 65 years of age.&#xD;
&#xD;
          2. Ability to provide written informed consent.&#xD;
&#xD;
          3. Mentally stable and able to comply with the procedures of the study protocol.&#xD;
&#xD;
          4. Type1 diabetes with onset of disease at &lt;40 years of age, insulin-dependence for &gt; 5&#xD;
             years at the time of enrollment&#xD;
&#xD;
          5. Absent stimulated c-peptide (&lt;0.3ng/mL) in response to a mixed meal tolerance test.&#xD;
&#xD;
          6. Involvement in intensive diabetes management&#xD;
&#xD;
          7. At least one episode of severe hypoglycemia in the 12 months prior to study&#xD;
             enrollment.&#xD;
&#xD;
          8. Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR A&#xD;
             Hypoglycemia score greater than or equal to the 90th percentile (1047) during the&#xD;
             screening period; OR Marked glycemic lability and defined by a lability index score&#xD;
             greater than or equal to the 90th percentile (433 mmol/L2/h•wk-1) during the screening&#xD;
             period; OR A composite of a Clarke score of 3 or less and a hypoglycemia score greater&#xD;
             than or equal to the 75th percentile (423) and a lability index greater than or equal&#xD;
             to the 75th percentile (329) during the screening period.&#xD;
&#xD;
          9. Subjects screening data from 20053135 protocol will be accepted for subjects eligible&#xD;
             for this study. If 20053135 visit was 12 months prior to enrollment, Visit 2&#xD;
             laboratory should be repeated.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Body Mass Index (BMI) &gt;30 kg/m2 or patient weight ≤50 kg.&#xD;
&#xD;
          2. Insulin requirement of &gt;1.0 IU/kg/day or &lt;15 U/day.&#xD;
&#xD;
          3. HbA1c &gt;10%.&#xD;
&#xD;
          4. Untreated proliferative diabetic retinopathy.&#xD;
&#xD;
          5. Blood Pressure: SBP &gt;160 mmHg or DBP &gt;100 mmHg.&#xD;
&#xD;
          6. Glomerular filtration rate &lt;80 mL/min/1.73 m2 (calculated).&#xD;
&#xD;
          7. Presence or history of macroalbuminuria (&gt;300mg/g creatinine).&#xD;
&#xD;
          8. Presence or history of panel-reactive anti-HLA antibodies.&#xD;
&#xD;
          9. For female subjects: Serum or urine Positive pregnancy test, presently breast-feeding,&#xD;
             or unwillingness to use effective contraceptive measures for the duration of the study&#xD;
             and 4 months after discontinuation. For male subjects: intent to procreate during the&#xD;
             duration of the study or within 4 months after discontinuation or unwillingness to use&#xD;
             effective measures of contraception. If sexually active, subject must use at least two&#xD;
             medically accepted methods of birth control.&#xD;
&#xD;
         10. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or&#xD;
             tuberculosis (TB).&#xD;
&#xD;
         11. Negative screen for Epstein-Barr Virus (EBV) by IgG determination.&#xD;
&#xD;
         12. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year&#xD;
             prior to study enrollment.&#xD;
&#xD;
         13. Any history of malignancy except for completely resected squamous or basal cell&#xD;
             carcinoma of the skin.&#xD;
&#xD;
         14. Active alcohol or substance abuse.&#xD;
&#xD;
         15. Hb below the lower limits of normal at the local laboratory; lymphopenia (&lt;1,000/µL),&#xD;
             neutropenia (&lt;1,500/µL), or thrombocytopenia (platelets &lt;100,000/µL).&#xD;
&#xD;
         16. A history of Factor V deficiency.&#xD;
&#xD;
         17. Any coagulopathy or medical condition requiring long-term anticoagulant therapy.&#xD;
&#xD;
         18. Severe co-existing cardiac disease,&#xD;
&#xD;
               1. recent myocardial infarction (within past 6 months)&#xD;
&#xD;
               2. evidence of ischemia on functional cardiac exam within the last year) left&#xD;
                  ventricular ejection fraction &lt;30%.&#xD;
&#xD;
         19. Persistent elevation of liver function tests at the time of study entry.&#xD;
&#xD;
         20. Symptomatic cholecystolithiasis.&#xD;
&#xD;
         21. Acute or chronic pancreatitis.&#xD;
&#xD;
         22. Symptomatic peptic ulcer disease.&#xD;
&#xD;
         23. Gastrointestinal disorders potentially interfering with the ability to absorb oral&#xD;
             medications.&#xD;
&#xD;
         24. Hyperlipidemia despite medical therapy (fasting LDL cholesterol &gt; 130 mg/dL, fasting&#xD;
             triglycerides &gt; 200 mg/dl).&#xD;
&#xD;
         25. Chronic use of systemic steroids, except for the use of ≤5 mg prednisone daily, or an&#xD;
             equivalent dose of hydrocortisone, for physiological replacement only.&#xD;
&#xD;
         26. Treatment with any anti-diabetic medications other than insulin within 4 weeks of&#xD;
             enrollment.&#xD;
&#xD;
        23. Use of any investigational agents within 4 weeks of enrollment. 24. Administration of&#xD;
        live attenuated vaccine(s) within 2 months of enrollment. 25. Any medical condition that,&#xD;
        in the opinion of the investigator, will interfere with the safe participation in the&#xD;
        trial.&#xD;
&#xD;
        26. Treatment with any immunosuppressive regimen at the time of enrollment. 27. A previous&#xD;
        islet transplant. 28. A previous pancreas transplant 29. Inflammatory bowel disease. 30.&#xD;
        History of intestinal obstructions. 31. Previous major abdominal surgery. 32. History of&#xD;
        peritonitis.&#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>Rodolfo Alejandro</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Diabetes Research Institute, University of Miami Miller School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>February 24, 2023</last_update_submitted>
  <last_update_submitted_qc>February 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Rodolfo Alejandro</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>islet transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>undecided. This is a small phase 1/2 pilot trial.</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/NCT02213003
org study id: 20140144
nct id: NCT02213003
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Current islet transplantation into the portal vein of the liver has shown the unique ability
      of islets to stabilize blood glucose levels and prevent severe hypoglycemia in a selected
      group of subjects with Type 1 diabetes. The main limitations of islet transplantation are the
      need for systemic immunosuppression to maintain function and the loss of islet function over
      time. Additionally, many studies have demonstrated that the current site of transplantation
      in the liver is not an ideal site due to several factors. These factors include (1)
      significant liver inflammation following islet infusion; (2) potential for life-threatening
      procedure-related complications such as bleeding and thrombosis; (3) high levels of
      immunosuppressive drugs and GI toxins in the liver contributing to islet toxicity; (4) the
      inability to retrieve islets after infusion; and (5) development of graft dysfunction in a
      number of recipients of intrahepatic allogeneic and autologous islets. The implantation of
      islets into the omentum will allow adequate engraftment of islets onto the omentum and will
      lead to comparable or superior functional and clinical outcomes than in the traditional
      intrahepatic site.
Islet transplantation will be performed in subjects with unstable Type 1 diabetes mellitus
      under permanent immunosuppression. Islets are re-suspended in autologous plasma and
      distributed on the omental surface by a minimal invasive approach. Cell adherence is achieved
      by addition of clinical-grade recombinant human thrombin that reacts with plasma to create a
      biocompatible, degradable gel containing the islet graft. The primary efficacy endpoint is
      the proportion of subjects with HbA1c ≤6.5% at 1 year AND free of severe hypoglycemic events
      from Day 28 to Day 365, inclusive, after the islet transplant. The primary safety endpoint is
      to demonstrate patient safety throughout all stages of the trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: A1c </= 6.5% and no severe hypoglycemia
time frame: 1 year
description: composite outcome
measure: procedural complications
time frame: 1 year
description: safety
arm group label: Islet transplantation
arm group type: Experimental
description: Transplantation of at least 5000 islet equivalents/kg of body weight onto the omentum.
intervention type: Biological
intervention name: Islet transplantation
description: Transplantation of at least 5000 islet equivalents/kg of body weight onto the Omentum.
arm group label: Islet transplantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Rodolfo Alejandro
role: Principal Investigator
affiliation: University of Miami
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Miami
investigator full name: Rodolfo Alejandro
investigator title: Professor of Medicine
mesh term: Diabetes Mellitus, Type 1
mesh term: Hypoglycemia
sharing ipd: Undecided
ipd description: undecided. This is a small phase 1/2 pilot trial.