<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/NCT04416737</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-57032</org_study_id>
    <secondary_id>1K23DK122017</secondary_id>
    <nct_id>NCT04416737</nct_id>
  </id_info>
  <brief_title>Evaluating the Benefits of Physiologic Insulin Delivery</brief_title>
  <official_title>Evaluating the Benefits of Physiologic Insulin Delivery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In normal physiology insulin is secreted by beta cells into the portal vein. There have been&#xD;
      a number of purported benefits among long-term intraperitoneal insulin users. In the present&#xD;
      study we will inject ultra-rapid acting insulin into the upper and lower peritoneum under&#xD;
      ultrasound guidance and compare it to subcutaneous injection. We will measure glucose,&#xD;
      insulin and glucagon following these injections, to assess for benefits in counter-regulatory&#xD;
      hormone production and insulin pharmacokinetics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The eventual goal of this line of work is an implanted insulin pump that delivers insulin&#xD;
      automatically into the peritoneum based on continuous glucose data. All prior intraperitoneal&#xD;
      pharmacokinetic studies used only concentrated regular insulin, which may be too slow to&#xD;
      provide full closed-loop insulin delivery without meal announcement. A description of&#xD;
      intraperitoneal ultra-rapid insulin kinetics, as well as counter-regulatory hormonal factors&#xD;
      that may counter hypoglycemia is needed. Upper versus lower peritoneal delivery may also&#xD;
      affect insulin kinetics. A possible benefit of intraperitoneal insulin is restoration of&#xD;
      glucagon response in longstanding diabetes and clearance of insulin by the liver, both of&#xD;
      which could provide hypoglycemic rescue in automated insulin delivery systems.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2021</start_date>
  <completion_date type="Actual">June 2, 2023</completion_date>
  <primary_completion_date type="Actual">June 2, 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>Crossover Assignment</intervention_model>
    <intervention_model_description>Participants will each come in for 3 visits separated by at least 1 week. During the first two visits they will be randomized to either upper or lower peritoneal injection followed by the other site. During the third visit a subcutaneous injection will be performed to provide comparative data to the standard of care.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Glucagon response to induced hypoglycemia</measure>
    <time_frame>Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max</time_frame>
    <description>For each injection site we will assess the change in glucagon from nadir to peak during induced hypoglycemia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin concentration in plasma</measure>
    <time_frame>Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose Values</measure>
    <time_frame>Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Upper Peritoneal, then Lower Peritoneal, then Subcutaneous</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lower Peritoneal, then Upper Peritoneal, then Subcutaneous</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ultra-rapid insulin</intervention_name>
    <description>Following 0.5-3 hours of insulin suspension from insulin pump, participants will receive insulin injection in respective locations (separated by at least 1 week) and then have serial lab measurements (YSI glucose, insulin and glucagon) taken during induced hypoglycemia.</description>
    <arm_group_label>Lower Peritoneal, then Upper Peritoneal, then Subcutaneous</arm_group_label>
    <arm_group_label>Upper Peritoneal, then Lower Peritoneal, then Subcutaneous</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18-60 years of age&#xD;
&#xD;
          2. Clinical diagnosis of type 1 diabetes&#xD;
&#xD;
          3. On insulin pump therapy and continuous glucose monitor (CGM) for at least 3 months&#xD;
&#xD;
          4. Ability to safely receive intraperitoneal injection&#xD;
&#xD;
          5. For females, not currently known to be pregnant&#xD;
&#xD;
          6. Understanding and willingness to follow the protocol and sign informed consent&#xD;
&#xD;
          7. Ability to speak, read and write in the language of the investigators&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diabetic ketoacidosis in the past 3 months&#xD;
&#xD;
          2. Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months&#xD;
             prior to enrollment&#xD;
&#xD;
          3. Pregnant or lactating&#xD;
&#xD;
          4. Active infection&#xD;
&#xD;
          5. A known medical condition that in the judgment of the investigator might interfere&#xD;
             with the completion of the protocol&#xD;
&#xD;
          6. Known cardiovascular events in the last 6 months&#xD;
&#xD;
          7. Known seizure disorder&#xD;
&#xD;
          8. Inpatient psychiatric treatment in the past 6 months&#xD;
&#xD;
          9. Lack of stability on medication 1 month prior to enrollment including&#xD;
             antihypertensive, thyroid, anti-depressant or lipid lowering medication.&#xD;
&#xD;
         10. Suspected drug or alcohol abuse&#xD;
&#xD;
         11. Chronic kidney disease (GFR &lt; 60 mL/min/1.73m^2)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rayhan Lal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 5, 2023</last_update_submitted>
  <last_update_submitted_qc>June 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Rayhan A. Lal</investigator_full_name>
    <investigator_title>Med+Peds Endocrinologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No current plan</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 14, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT04416737/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04416737
org study id: IRB-57032
secondary id: 1K23DK122017
nct id: NCT04416737
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
In normal physiology insulin is secreted by beta cells into the portal vein. There have been
      a number of purported benefits among long-term intraperitoneal insulin users. In the present
      study we will inject ultra-rapid acting insulin into the upper and lower peritoneum under
      ultrasound guidance and compare it to subcutaneous injection. We will measure glucose,
      insulin and glucagon following these injections, to assess for benefits in counter-regulatory
      hormone production and insulin pharmacokinetics.
The eventual goal of this line of work is an implanted insulin pump that delivers insulin
      automatically into the peritoneum based on continuous glucose data. All prior intraperitoneal
      pharmacokinetic studies used only concentrated regular insulin, which may be too slow to
      provide full closed-loop insulin delivery without meal announcement. A description of
      intraperitoneal ultra-rapid insulin kinetics, as well as counter-regulatory hormonal factors
      that may counter hypoglycemia is needed. Upper versus lower peritoneal delivery may also
      affect insulin kinetics. A possible benefit of intraperitoneal insulin is restoration of
      glucagon response in longstanding diabetes and clearance of insulin by the liver, both of
      which could provide hypoglycemic rescue in automated insulin delivery systems.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Participants will each come in for 3 visits separated by at least 1 week. During the first two visits they will be randomized to either upper or lower peritoneal injection followed by the other site. During the third visit a subcutaneous injection will be performed to provide comparative data to the standard of care.
primary purpose: Other
masking: None (Open Label)
measure: Glucagon response to induced hypoglycemia
time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
description: For each injection site we will assess the change in glucagon from nadir to peak during induced hypoglycemia.
measure: Insulin concentration in plasma
time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
measure: Glucose Values
time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
arm group label: Upper Peritoneal, then Lower Peritoneal, then Subcutaneous
arm group type: Experimental
description: Ultra-fast acting insulin will be injected into the upper peritoneum then lower peritoneum then subcutaneous space.
arm group label: Lower Peritoneal, then Upper Peritoneal, then Subcutaneous
arm group type: Experimental
description: Ultra-fast acting insulin will be injected into the lower peritoneum then upper peritoneum then subcutaneous space.
intervention type: Other
intervention name: Ultra-rapid insulin
description: Following 0.5-3 hours of insulin suspension from insulin pump, participants will receive insulin injection in respective locations (separated by at least 1 week) and then have serial lab measurements (YSI glucose, insulin and glucagon) taken during induced hypoglycemia.
arm group label: Lower Peritoneal, then Upper Peritoneal, then Subcutaneous
arm group label: Upper Peritoneal, then Lower Peritoneal, then Subcutaneous
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Rayhan Lal, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Rayhan A. Lal
investigator title: Med+Peds Endocrinologist
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin
sharing ipd: No
ipd description: No current plan
provided document: 