<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/NCT01684956</url>
  </required_header>
  <id_info>
    <org_study_id>2012P001098</org_study_id>
    <nct_id>NCT01684956</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Type 1 Diabetes</brief_title>
  <official_title>Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Volunteers With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are doing this research study to find out if the type of needle used to&#xD;
      administer them affects the speed with which insulin and glucagon get into the blood. The&#xD;
      investigators will compare a traditional insulin needle to an injection device, called the&#xD;
      MicronJet, that uses microneedles to deliver medication into the top layer of your skin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Aggregate mean difference in tmax between the delivery methods (the insulin and glucagon data will be evaluated separately)</measure>
    <time_frame>1 day</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Aggregate mean difference in t1/2max between the methods</measure>
    <time_frame>1 day visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregate mean difference in Cmax between the methods</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregate mean difference in area under the curve (AUC) between methods</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of 0-1 hour (and by subtraction hours 1-5)</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of 0-2 hours (and by subtraction hours 2-5)</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to 50% of Total AUC (or said another way, time to 50% exposure)</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of subjects with difference in tmax between the methods of &gt; 25%</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of &quot;dry&quot; injections with no reflux of fluid from the injection site</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in mean visual analog pain score between the two methods</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in mean visual analog pain score between insulin and glucagon with subcutaneous injection</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in mean visual analog pain score between insulin and glucagon with intradermal injection</measure>
    <time_frame>1 day</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Intradermal first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intradermal injection experiment first, followed by subcutaneous injection experiment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subcutaneous first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection experiment first, followed by intradermal injection experiment</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intradermal injection</intervention_name>
    <arm_group_label>Intradermal first</arm_group_label>
    <arm_group_label>Subcutaneous first</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Subcutaneous injection</intervention_name>
    <arm_group_label>Intradermal first</arm_group_label>
    <arm_group_label>Subcutaneous first</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older with clinical type 1 diabetes for at least one year&#xD;
&#xD;
          -  Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting&#xD;
             insulins including insulin aspart (Novolog), insulin lispro (Humalog), and insulin&#xD;
             glulisine (Apidra).&#xD;
&#xD;
          -  Ability to consume a sufficient amount of carbohydrates over 2-3 hours to cover 5&#xD;
             units of rapid acting insulin&#xD;
&#xD;
          -  Stimulated C-peptide &lt;0.1 nmol/L at 90 minutes after liquid mixed meal tolerance test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Unable to comply with study procedures&#xD;
&#xD;
          -  Current participation in another diabetes-related clinical trial other than one that&#xD;
             is primarily observational in nature. Potential subjects enrolled in trails of passive&#xD;
             monitoring equipment, such as continuous glucose monitors (CGMs), are not excluded&#xD;
&#xD;
          -  Inadequate venous access as determined by study nurse or physician at time of&#xD;
             screening&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Hemoglobin less than 13.5 for men and less than 12 for women&#xD;
&#xD;
          -  History of pheochromocytoma (fractionated metanephrines will be tested in patients&#xD;
             with history increasing the risk for a catecholamine secreting tumor to include&#xD;
             episodic or treatment refractory hypertension defined as requiring 4 or more&#xD;
             medications to achieve normotension, paroxysms of tachycardia, pallor, or headache, or&#xD;
             personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau&#xD;
             disease)&#xD;
&#xD;
          -  History of adverse reaction to glucagon (including allergy) besides nausea and&#xD;
             vomiting&#xD;
&#xD;
          -  History of adrenal disease or tumor&#xD;
&#xD;
          -  Hypertension (blood pressure &gt; 160/100 mm/Hg at screening or day of study visit&#xD;
&#xD;
          -  History of allergy to aspirin or any history of aspirin intolerance, including Reye's&#xD;
             syndrome, or gastric ulcer or bleeding associated with salicylates.&#xD;
&#xD;
          -  Blood dyscrasia or bleeding diathesis, such as hemophilia, Von Willebrand's disorder,&#xD;
             and idiopathic thrombocytopenic purpura (ITP)&#xD;
&#xD;
          -  Peptic Ulcer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven J Russell, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <last_update_submitted>September 6, 2016</last_update_submitted>
  <last_update_submitted_qc>September 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 7, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Steven J. Russell, MD, PhD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>intradermal</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>microneedle</keyword>
  <keyword>insulin</keyword>
  <keyword>glucagon</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>October 19, 2020</submitted>
    <returned>November 12, 2020</returned>
    <submitted>March 28, 2022</submitted>
    <submission_canceled>April 1, 2022</submission_canceled>
    <submitted>April 4, 2022</submitted>
    <returned>October 25, 2022</returned>
    <submitted>November 10, 2022</submitted>
    <returned>September 14, 2023</returned>
  </pending_results>
  <!-- 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/NCT01684956
org study id: 2012P001098
nct id: NCT01684956
lead sponsor: 
has dmc: No
The investigators are doing this research study to find out if the type of needle used to
      administer them affects the speed with which insulin and glucagon get into the blood. The
      investigators will compare a traditional insulin needle to an injection device, called the
      MicronJet, that uses microneedles to deliver medication into the top layer of your skin.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Aggregate mean difference in tmax between the delivery methods (the insulin and glucagon data will be evaluated separately)
time frame: 1 day
measure: Aggregate mean difference in t1/2max between the methods
time frame: 1 day visit
measure: Aggregate mean difference in Cmax between the methods
time frame: 1 day
measure: Aggregate mean difference in area under the curve (AUC) between methods
time frame: 1 day
measure: AUC of 0-1 hour (and by subtraction hours 1-5)
time frame: 1 day
measure: AUC of 0-2 hours (and by subtraction hours 2-5)
time frame: 1 day
measure: Time to 50% of Total AUC (or said another way, time to 50% exposure)
time frame: 1 day
measure: Fraction of subjects with difference in tmax between the methods of > 25%
time frame: 1 day
measure: Fraction of "dry" injections with no reflux of fluid from the injection site
time frame: 1 day
measure: Difference in mean visual analog pain score between the two methods
time frame: 1 day
measure: Difference in mean visual analog pain score between insulin and glucagon with subcutaneous injection
time frame: 1 day
measure: Difference in mean visual analog pain score between insulin and glucagon with intradermal injection
time frame: 1 day
arm group label: Intradermal first
arm group type: Experimental
description: Intradermal injection experiment first, followed by subcutaneous injection experiment
arm group label: Subcutaneous first
arm group type: Experimental
description: Subcutaneous injection experiment first, followed by intradermal injection experiment
intervention type: Procedure
intervention name: Intradermal injection
arm group label: Intradermal first
arm group label: Subcutaneous first
intervention type: Procedure
intervention name: Subcutaneous injection
arm group label: Intradermal first
arm group label: Subcutaneous first
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Steven J Russell, MD, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Steven J. Russell, MD, PhD
investigator title: Associate Professor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
submitted: October 19, 2020
returned: November 12, 2020
submitted: March 28, 2022
submission canceled: April 1, 2022
submitted: April 4, 2022
returned: October 25, 2022
submitted: November 10, 2022
returned: September 14, 2023