<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/NCT03779139</url>
  </required_header>
  <id_info>
    <org_study_id>SURG-2017-26057</org_study_id>
    <nct_id>NCT03779139</nct_id>
  </id_info>
  <brief_title>Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis</brief_title>
  <acronym>iSite</acronym>
  <official_title>A Randomized Trial of Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized pilot trial of patients (n=30) undergoing Total Pancreatectomy and Islet&#xD;
      AutoTransplant (TPIAT). Patients with islet harvest of greater than 5000 islet equivalents/kg&#xD;
      body weight will be randomized to receive a portion of their islets into an omental pouch.&#xD;
      For outcomes related to islet function, a group of normal volunteers (n=15) will be studied&#xD;
      as a comparator group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic pancreatitis affects as many as 1 in every 2,500 persons and is associated with&#xD;
      incapacitating pain, frequent hospitalization and risk of narcotic dependence. This is a&#xD;
      debilitating disease with limited treatment options; afflicted patients are often young or&#xD;
      middle aged adults. The health and economic costs of pancreatitis are great. Nearly $300&#xD;
      million is spent on emergency department visits alone in the US each year. More than 90% of&#xD;
      patients with chronic pancreatitis have been hospitalized, half use narcotic analgesics&#xD;
      regularly, and one-fourth are on disability. The lifetime risk of diabetes mellitus is as&#xD;
      high as 70%. This proposal addresses needs in two broad topic areas: pancreatitis, and&#xD;
      diabetes. The investigators propose to investigate a new technique for implanting autologous&#xD;
      pancreatic islet cells into patients undergoing surgery for acute recurrent or chronic&#xD;
      pancreatitis in an effort to improve long-term diabetes control.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</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>Portal vein thrombosis</measure>
    <time_frame>Post operative day 4 or 5.</time_frame>
    <description>Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clavien-Dindo classification of surgical complications</measure>
    <time_frame>Within 30 days of surgery</time_frame>
    <description>Grades surgical complications based on the level of treatment necessary to treat the complication.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mixed Meal Tolerance Test</measure>
    <time_frame>1 year</time_frame>
    <description>Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intravenous Glucose tolerance test</measure>
    <time_frame>1 year</time_frame>
    <description>Patients are given a bolus of 0.2mg/kg of dextrose at t=0. Blood samples will be drawn at t=-10,-5,-1,2,3,4,5,7 and 10 minutes</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glucose potentiated arginine stimulation</measure>
    <time_frame>1 year</time_frame>
    <description>Starting immediately after glucose tolerance test (time t=10 minutes), 20% dextrose will be infused to maintain a glucose ~230mg/dL until test is completed. Glucose levels are measured every 5 minutes to maintain glucose in the target range after 40 minutes of continuous 20% dextrose infusion, After 40 minutes of continuous D20% infusion, baseline samples for glucose, insulin, and C-peptide are drawn (three samples over 10 minutes), a bolus of 5 grams arginine is given (at time 55 minutes), and samples for glucose, insulin, and C-peptide are taken at 2, 3, 4, and 5 minutes after&#xD;
the arginine bolus.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypoglycemic clamp</measure>
    <time_frame>1 year</time_frame>
    <description>A stepped hypoglycemic clamp protocol with variable glucose infusion rates will be performed to achieve 45 min glucose plateaus at 70, 60, and 50 mg/dl.Glucagon responses will be calculated by subtracting the mean of the three baseline values observed prior to the clamp from glucagon levels observed at 70, 60, and 50 mg/dl glucose nadirs during the clamp</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Continuous glucose monitoring</measure>
    <time_frame>1 year</time_frame>
    <description>3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hemoglobin A1c levels</measure>
    <time_frame>1 year</time_frame>
    <description>Measure of average glucose levels over last several weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Insulin Use</measure>
    <time_frame>1 year</time_frame>
    <description>calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypoglycemic episodes</measure>
    <time_frame>1 year</time_frame>
    <description>All severe hypoglycemic events will be recorded. This is defined based on American Diabetes Association criteria as a hypoglycemic episode &lt;54 mg/dL or (if not measured) associated with prompt recovery upon administration of glucose in which a patient is mentally or physically incapacitated and requires assistance from another person to treat the hypoglycemia.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clarke score</measure>
    <time_frame>1 year</time_frame>
    <description>is determined from eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia; it evaluates symptomatic responses to hypoglycemia. A score of 4 or greater suggests impaired awareness of hypoglycemia</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Chronic Pancreatitis</condition>
  <condition>Diabetes Mellitus</condition>
  <condition>Islet Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>Intrahepatic islets alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Intrahepatic and omental pouch islets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Volunteers</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intrahepatic islets and islets in the omental pouch</intervention_name>
    <description>Patients with islet harvest of &gt;5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to 4000 IEq/kg delivered via intraportal route and the remainder implanted into a constructed omental pouch.</description>
    <arm_group_label>Intrahepatic and omental pouch islets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intrahepatic islets alone</intervention_name>
    <description>This is the standard of care procedure. Patients with islet harvest of &gt;5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to all islets autotransplanted intrahepatically via the intraportal route.</description>
    <arm_group_label>Intrahepatic islets alone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Normal Volunteers</intervention_name>
    <description>These individuals will undergo metabolic testing as well as islet cell function testing.</description>
    <arm_group_label>Normal Volunteers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-68&#xD;
&#xD;
          2. Scheduled for total pancreatectomy and IAT at U of MN. All patients who are approved&#xD;
             for pancreatectomy and IAT at U of MN are reviewed by a multi-disciplinary committee&#xD;
             including surgeons, gastroenterologists specializing in pancreatic disease, a pain&#xD;
             specialist psychologist, and endocrinologist to confirm the diagnosis of chronic&#xD;
             pancreatitis and candidate suitability for surgery.&#xD;
&#xD;
          3. Able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pre-Existing diabetes mellitus fasting blood glucose&gt;115mg/dl, or hemoglobin A1c level&#xD;
             &gt;6.0% because these are all evidence of inadequate beta-cello mass.&#xD;
&#xD;
          2. Use of any of the following treatments in the 30 days prior to enrollment: insulin,&#xD;
             metformin, sulfonylureas, glinides, thiazolidinediones, GLP-1 agonists, DPP-4&#xD;
             inhibitors, or amylin.&#xD;
&#xD;
          3. ALT or AST&gt;2.5 times the upper limit of normal (ULN). Bilirubin&gt;ULN, unless due to&#xD;
             benign diagnosis such as Gilbert's.&#xD;
&#xD;
          4. Any of the following hematologic abnormalities: server anemia (hemoglobin &lt;10 g/dL),&#xD;
             thrombocytopenia (&lt;150/mm3), or neutropenia(&lt;1.0 x 109/L).&#xD;
&#xD;
          5. Current use or expected use of oral or injected corticosteroids, or any mediation&#xD;
             likely to affect glucose tolerance. However, use of hydrocortisone for physiologic&#xD;
             replacement, or use of any topical, inhaled or intranasal glucocorticoid is permitted.&#xD;
&#xD;
          6. Current or expected use of any other immunosuppressive agent.&#xD;
&#xD;
          7. Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin,&#xD;
             enoxaparin), or any history of pulmonary embolism.&#xD;
&#xD;
          8. For females, plans to become pregnant or unwillingness to use birth control for the&#xD;
             study duration.&#xD;
&#xD;
          9. Inability to comply with the study protocol.&#xD;
&#xD;
         10. Untreated psychiatric illness that may interfere with ability to give informed&#xD;
             consent, or other developmental delay or neurocognitive disorder that impairs with a&#xD;
             patient's ability to consent on their own behalf.&#xD;
&#xD;
         11. Any other medical condition that , in the opinion of the investigator, may interfere&#xD;
             wit the patient's ability to successfully and safely complete the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>68 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Greg Beilman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota, Department of Surgery</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kristine Mulier</last_name>
    <phone>612-625-0654</phone>
    <email>groeh001@umn.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Greg Beilman</last_name>
      <phone>612-625-7911</phone>
      <email>beilm001@umn.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>September 16, 2022</last_update_submitted>
  <last_update_submitted_qc>September 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>total pancreatectomy with islet autotransplant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatitis</mesh_term>
    <mesh_term>Pancreatitis, Chronic</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/NCT03779139
org study id: SURG-2017-26057
nct id: NCT03779139
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Randomized pilot trial of patients (n=30) undergoing Total Pancreatectomy and Islet
      AutoTransplant (TPIAT). Patients with islet harvest of greater than 5000 islet equivalents/kg
      body weight will be randomized to receive a portion of their islets into an omental pouch.
      For outcomes related to islet function, a group of normal volunteers (n=15) will be studied
      as a comparator group.
Chronic pancreatitis affects as many as 1 in every 2,500 persons and is associated with
      incapacitating pain, frequent hospitalization and risk of narcotic dependence. This is a
      debilitating disease with limited treatment options; afflicted patients are often young or
      middle aged adults. The health and economic costs of pancreatitis are great. Nearly $300
      million is spent on emergency department visits alone in the US each year. More than 90% of
      patients with chronic pancreatitis have been hospitalized, half use narcotic analgesics
      regularly, and one-fourth are on disability. The lifetime risk of diabetes mellitus is as
      high as 70%. This proposal addresses needs in two broad topic areas: pancreatitis, and
      diabetes. The investigators propose to investigate a new technique for implanting autologous
      pancreatic islet cells into patients undergoing surgery for acute recurrent or chronic
      pancreatitis in an effort to improve long-term diabetes control.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Portal vein thrombosis
time frame: Post operative day 4 or 5.
description: Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.
measure: Clavien-Dindo classification of surgical complications
time frame: Within 30 days of surgery
description: Grades surgical complications based on the level of treatment necessary to treat the complication.
measure: Mixed Meal Tolerance Test
time frame: 1 year
description: Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.
measure: Intravenous Glucose tolerance test
time frame: 1 year
description: Patients are given a bolus of 0.2mg/kg of dextrose at t=0. Blood samples will be drawn at t=-10,-5,-1,2,3,4,5,7 and 10 minutes
measure: Glucose potentiated arginine stimulation
time frame: 1 year
description: Starting immediately after glucose tolerance test (time t=10 minutes), 20% dextrose will be infused to maintain a glucose ~230mg/dL until test is completed. Glucose levels are measured every 5 minutes to maintain glucose in the target range after 40 minutes of continuous 20% dextrose infusion, After 40 minutes of continuous D20% infusion, baseline samples for glucose, insulin, and C-peptide are drawn (three samples over 10 minutes), a bolus of 5 grams arginine is given (at time 55 minutes), and samples for glucose, insulin, and C-peptide are taken at 2, 3, 4, and 5 minutes after
the arginine bolus.
measure: Hypoglycemic clamp
time frame: 1 year
description: A stepped hypoglycemic clamp protocol with variable glucose infusion rates will be performed to achieve 45 min glucose plateaus at 70, 60, and 50 mg/dl.Glucagon responses will be calculated by subtracting the mean of the three baseline values observed prior to the clamp from glucagon levels observed at 70, 60, and 50 mg/dl glucose nadirs during the clamp
measure: Continuous glucose monitoring
time frame: 1 year
description: 3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia
measure: Hemoglobin A1c levels
time frame: 1 year
description: Measure of average glucose levels over last several weeks
measure: Insulin Use
time frame: 1 year
description: calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90
measure: Hypoglycemic episodes
time frame: 1 year
description: All severe hypoglycemic events will be recorded. This is defined based on American Diabetes Association criteria as a hypoglycemic episode <54 mg/dL or (if not measured) associated with prompt recovery upon administration of glucose in which a patient is mentally or physically incapacitated and requires assistance from another person to treat the hypoglycemia.
measure: Clarke score
time frame: 1 year
description: is determined from eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia; it evaluates symptomatic responses to hypoglycemia. A score of 4 or greater suggests impaired awareness of hypoglycemia
arm group label: Intrahepatic islets alone
arm group type: Active Comparator
arm group label: Intrahepatic and omental pouch islets
arm group type: Experimental
arm group label: Normal Volunteers
arm group type: Sham Comparator
intervention type: Procedure
intervention name: Intrahepatic islets and islets in the omental pouch
description: Patients with islet harvest of >5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to 4000 IEq/kg delivered via intraportal route and the remainder implanted into a constructed omental pouch.
arm group label: Intrahepatic and omental pouch islets
intervention type: Procedure
intervention name: Intrahepatic islets alone
description: This is the standard of care procedure. Patients with islet harvest of >5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to all islets autotransplanted intrahepatically via the intraportal route.
arm group label: Intrahepatic islets alone
intervention type: Other
intervention name: Normal Volunteers
description: These individuals will undergo metabolic testing as well as islet cell function testing.
arm group label: Normal Volunteers
criteria: 
gender: All
minimum age: 18 Years
maximum age: 68 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Greg Beilman, MD
role: Principal Investigator
affiliation: University of Minnesota, Department of Surgery
last name: Kristine Mulier
phone: 612-625-0654
email: groeh001@umn.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatitis
mesh term: Pancreatitis, Chronic
sharing ipd: No