<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/NCT04409587</url>
  </required_header>
  <id_info>
    <org_study_id>MDEC2018</org_study_id>
    <nct_id>NCT04409587</nct_id>
  </id_info>
  <brief_title>Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump</brief_title>
  <acronym>BIG LEAP</acronym>
  <official_title>Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump: A Comparison of Insulin Degludec to Continuous Subcutaneous Infusion of Insulin Aspart for Basal Insulin Delivery in Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mountain Diabetes and Endocrine Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mountain Diabetes and Endocrine Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this investigator-initiated trial is to compare the effect of a daily&#xD;
      injection of insulin degludec vs. basal insulin delivery via Continuous Subcutaneous Insulin&#xD;
      Infusion (CSII), both in combination with bolus insulin delivery via the patient's usual&#xD;
      insulin pump with insulin aspart, on glycemic variability, overall blood glucose control and&#xD;
      incidence of hypoglycemia, all assessed by continuous glucose monitor (CGM), as well as&#xD;
      patient satisfaction, in patients with type 1 diabetes currently using CSII.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this trial is to determine whether insulin degludec will provide an&#xD;
      equally stable and consistent basal glycemic profile with lower glycemic variability as&#xD;
      determined by Continuous Glucose Monitoring compared to insulin aspart delivered by&#xD;
      Continuous Subcutaneous Insulin Infusion in patients with type 1 diabetes experienced in use&#xD;
      of insulin pump therapy. Specifically, this study will determine if the percent time in the&#xD;
      target glycemic range (70 to 180 mg/dl) by Continuous Glucose Monitoring is superior using&#xD;
      insulin degludec than continuously infused insulin aspart, and if degludec is associated with&#xD;
      lower glucose variability as assessed by the standard deviation (SD) of the mean daily&#xD;
      glucose by Continuous Glucose Monitoring. Particular attention will be given to the nocturnal&#xD;
      glucose profile (from midnight to 6 am) which most closely reflects basal insulin action as&#xD;
      it is typically the time of day least affected by bolus insulin, food intake or exercise.&#xD;
      Quality of life questionnaires regarding treatment preference will be used to capture patient&#xD;
      preference for method of basal insulin delivery.&#xD;
&#xD;
      RESEARCH DESIGN AND METHODS&#xD;
&#xD;
      Study hypothesis:&#xD;
&#xD;
      It is anticipated, based on the low glycemic variability of insulin degludec shown in glucose&#xD;
      clamp studies and seen in clinical practice, that insulin degludec will provide more stable&#xD;
      24 hour basal insulin action than insulin aspart by Continuous Subcutaneous Insulin Infusion&#xD;
      (CSII) in patients with type 1 diabetes.&#xD;
&#xD;
      Primary endpoint:&#xD;
&#xD;
      Percent time in euglycemia (BG 70 to 180 mg/dl) by Continuous Glucose Monitoring (CGM) during&#xD;
      the final 14 days of each treatment period during steady state (with basal insulin delivery&#xD;
      as either one daily injection of insulin degludec or as insulin aspart via CSII).&#xD;
&#xD;
      Study type:&#xD;
&#xD;
      This will be a randomized, cross-over, open label, single-center study consisting of a 20&#xD;
      week period on each of two basal insulin delivery methods, both in combination with insulin&#xD;
      aspart with boluses taken by insulin pump. Each 20 week period will consist of a 4 week&#xD;
      insulin optimization period for titration of basal and bolus insulin doses, followed by a 16&#xD;
      week maintenance period. The final 2 weeks of the maintenance period during each treatment&#xD;
      arm will be used for endpoint data collection. The treatment sequence will occur in random&#xD;
      order. The study population will include patients with type 1 diabetes with good baseline&#xD;
      glycemic control who are experienced in the use of both CSII and CGM; the cross-over design&#xD;
      allows each subject to serve as his or her own control.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 12, 2018</start_date>
  <completion_date type="Actual">November 1, 2020</completion_date>
  <primary_completion_date type="Actual">May 16, 2020</primary_completion_date>
  <phase>Phase 4</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>This will be a randomized, cross-over, open label, single-center study consisting of a 20 week period on each of two basal insulin delivery methods, both in combination with insulin aspart with boluses taken by insulin pump. Each 20 week period will consist of a 4 week insulin optimization period for titration of basal and bolus insulin doses, followed by a 16 week maintenance period. The final 2 weeks of the maintenance period during each treatment arm will be used for endpoint data collection. The treatment sequence will occur in random order. The study population will include patients with type 1 diabetes with good baseline glycemic control who are experienced in the use of both Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitor; the cross-over design allows each subject to serve as his or her own control.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This is an unblinded study as the two basal insulin delivery methods (degludec via injection vs. aspart via CSII) cannot be blinded. One group of patients will first use degludec for 20 weeks then switch to CSII for 20 weeks. As all eligible patients who sign the IRB consent form are identified, a random number will be generated to determine the treatment with which they begin first. The other group of patients will start with CSII and after 20 weeks switch to Tresiba for 20 weeks. Randomization sequence will be determined by computerized randomization program. All patients will receive both treatments unless they drop out. Dropouts are unlikely since the participants are all regular continuing patients of the site's clinical practice.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM</measure>
    <time_frame>46 weeks</time_frame>
    <description>Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM during the final 14 days of each treatment period during steady state (with basal insulin delivery as either one daily injection of insulin degludec or as insulin aspart via CSII)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Standard Deviation (SD) of blood glucose by CGM for two week period</measure>
    <time_frame>46 weeks</time_frame>
    <description>SD of interstitial fluid glucose by CGM for 2 week period during each basal insulin delivery method. (Note: because the Dexcom Platinum G5 CGM is currently only FDA approved for 7 days of use, two contiguous CGM periods using 2 sensors, each for 7 days, will be performed to capture 2 weeks of continuous CGM data.) Dexcom G6 is approved by FDA for 10 days of use so 2 sensors will be used during the CGM periods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SD of blood glucose by CGM during the nocturnal period</measure>
    <time_frame>46 weeks</time_frame>
    <description>SD of blood glucose by CGM during the nocturnal period (midnight to 6 am) during each basal insulin delivery method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent time in hypoglycemia by CGM</measure>
    <time_frame>46 weeks</time_frame>
    <description>Percent time in hypoglycemia by CGM, captured at 2 levels of hypoglycemia: BG &lt; 54 mg/dl (level 2) and BG 55-69 mg/dl (level 1), for each basal insulin treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent time in normoglycemia</measure>
    <time_frame>46 weeks</time_frame>
    <description>Percent time in normoglycemia (BG 70 to 140 mg/dl) by CGM during each basal treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to recovery from level 2 hypoglycemia</measure>
    <time_frame>46 weeks</time_frame>
    <description>Time to recovery from level 2 hypoglycemia (BG &gt;70 with resolution of symptoms) on each treatment. If a second event (BG &lt; 70 mg/dl) occurs within 60 minutes of a previous hypoglycemic event, this will be considered part of the same hypoglycemic episode.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>46 weeks</time_frame>
    <description>Patient satisfaction by TRIM-D questionnaires with each basal insulin treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>46 weeks</time_frame>
    <description>Patient satisfaction by TRIM-DD questionnaires with each basal insulin treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c</measure>
    <time_frame>46 weeks</time_frame>
    <description>HbA1c after 20 weeks of each basal insulin treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily insulin dosage</measure>
    <time_frame>46 weeks</time_frame>
    <description>Total daily insulin dose, total basal insulin dose, and total bolus insulin dose on each treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Type1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>NovoLog®-only</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In the aspart-Only group, the subject will only take aspart through the their pump. This study population will have an established expertise in diabetes self-management with previous knowledge of insulin pump therapy and Dexcom Continuous Glucose Monitoring (CGM). Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses. Aspart is put into their pump and delivered to their body through a small tube placed under your skin. In this NovoLog®-only treatment group, the subject will take aspart with each meal while your pump also gives you a slow, continuous dose of aspart for basal insulin. This treatment group is very similar (or even identical) to the treatment the subject was receiving prior to starting the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Novolog® and Tresiba® Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This study population will have an expertise in diabetes self-management with their insulin pump and Dexcom CGM. In the Novolog® and Tresiba® group, the subject will still take aspart via their pump for meals and correction boluses, but they will reduce the slow trickle (basal insulin) programmed in their pump to almost zero. Instead of receiving their normal basal insulin via CSII, the subject will injected degludec once or twice daily from an insulin pen for your basal insulin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspart</intervention_name>
    <description>A population of well controlled patients with type 1 diabetes who are experienced in the use of both Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitor (CGM) was chosen in order to assess the effect of the change in glycemic profile using two different methods of basal insulin delivery. Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses.&#xD;
Replacing basal insulin delivery by CSII with a single daily injection of degludec will add minimal, if any, treatment burden which will be offset by potential therapeutic benefits. These benefits include the potential for reduced glycemic variability and the elimination of the risk of hyperglycemia and DKA with basal insulin interruption which can occur with infusion set occlusion or disgorging inherent to Continuous Subcutaneous Insulin Infusion.</description>
    <arm_group_label>Novolog® and Tresiba® Group</arm_group_label>
    <other_name>Degludec</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients &gt; 18 years of age with type 1 diabetes using CSII with any&#xD;
             pump for &gt; 12 months.&#xD;
&#xD;
          2. Females must be using adequate contraception, defined as oral contraceptive pill,&#xD;
             barrier method of contraception, or surgical method (tubal ligation or hysterectomy).&#xD;
&#xD;
          3. Good glycemic control (HbA1c &lt; 8.0%).&#xD;
&#xD;
          4. Patients are experienced in carbohydrate counting, evidenced by pump downloads showing&#xD;
             frequent meal boluses with realistic carbohydrate entries, few over-rides of the pump&#xD;
             bolus calculator, few to no omitted boluses (at least 3 boluses per day), and&#xD;
             post-meal glucose levels generally below 200 mg/dl indicating accurate carbohydrate&#xD;
             assessment.&#xD;
&#xD;
          5. Patients are regular (&gt;85% of time) users of the Dexcom G5 or G6 CGM.&#xD;
&#xD;
          6. Pump download confirms correct use of insulin pump features, including appropriate use&#xD;
             of bolus calculator with minimal overrides, entering carbohydrate content of meals, at&#xD;
             least 3 boluses taken per day, appropriate use of correction boluses, and infusion set&#xD;
             changes every 2 to 3 days.&#xD;
&#xD;
          7. No serious comorbidities including: retinopathy requiring active intervention, eGFR &lt;&#xD;
             30, CV event within the previous 6 months, active malignancy with ongoing treatment,&#xD;
             any condition requiring chronic use of systemic glucocorticoids, or any other&#xD;
             condition which in the opinion of the investigator would interfere with the subject's&#xD;
             ability to comply with the study protocol or acutely affect insulin requirements.&#xD;
&#xD;
          8. Able to comply with study protocol.&#xD;
&#xD;
          9. Ability to provide written informed consent prior to any study-related procedures.&#xD;
&#xD;
             -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with type 2 diabetes.&#xD;
&#xD;
          2. Subjects with HbA1c &gt; 8.0%&#xD;
&#xD;
          3. Subjects not using CSII and CGM (ie, on MDI)&#xD;
&#xD;
          4. Subjects inexperienced in the use of CSII, or whose pump download shows poor&#xD;
             utilization of bolus calculator features, ie fewer than 2 boluses per day, lack of&#xD;
             correction boluses, frequent overrides of the recommended boluses, unrealistic&#xD;
             carbohydrate entries (suggestive of under-bolusing), not changing infusion set at&#xD;
             least every 3 days, or other evidence of poor insulin pump usage.&#xD;
&#xD;
          5. Subjects inexperienced in or not regular users (&gt;85% of time) of Dexcom G5 or G6 CGM&#xD;
&#xD;
          6. Subjects who are using a Medtronic pump with low blood glucose suspend who are&#xD;
             unwilling to use the Dexcom CGM or to disengage the low blood glucose suspend feature&#xD;
             of the pump.&#xD;
&#xD;
          7. Use of any other CGM than Dexcom G5 or G6.&#xD;
&#xD;
          8. Serious concomitant illness.&#xD;
&#xD;
          9. Females unwilling to use adequate contraception, intending to become pregnant, or&#xD;
             breastfeeding.&#xD;
&#xD;
         10. Known or suspected allergy to study products, their excipients or related products.&#xD;
&#xD;
         11. Previous participation in this trial. Note: subjects who screen fail because of A1c&#xD;
             may rescreen once if, in the opinion of the investigator, the HbA1c was explainable&#xD;
             (ie, recent steroid injection or illness, etc) and atypical for the subject.&#xD;
&#xD;
         12. Hypoglycemic unawareness.&#xD;
&#xD;
         13. Episode of severe hypoglycemia (requiring assistance for treatment) within the&#xD;
             previous 90 days.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mountain Diabetes and Endocrine Center</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://online.liebertpub.com/doi/full/10.1089/DIA.2017.0175</url>
    <description>Hauzenber JR et al. Diab Technol Therapeutics 2017</description>
  </link>
  <results_reference>
    <citation>Misso ML, Egberts KJ, Page M, O'Connor D, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD005103. doi: 10.1002/14651858.CD005103.pub2.</citation>
    <PMID>20091571</PMID>
  </results_reference>
  <results_reference>
    <citation>Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, Maahs DM, Tamborlane WV; T1D Exchange Clinic Network. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015 Jun;38(6):971-8. doi: 10.2337/dc15-0078.</citation>
    <PMID>25998289</PMID>
  </results_reference>
  <results_reference>
    <citation>Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012 Sep;14(9):859-64. doi: 10.1111/j.1463-1326.2012.01627.x. Epub 2012 Jun 7.</citation>
    <PMID>22594461</PMID>
  </results_reference>
  <results_reference>
    <citation>Lane W, Bailey TS, Gerety G, Gumprecht J, Philis-Tsimikas A, Hansen CT, Nielsen TSS, Warren M; Group Information; SWITCH 1. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):33-44. doi: 10.1001/jama.2017.7115.</citation>
    <PMID>28672316</PMID>
  </results_reference>
  <results_reference>
    <citation>Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available.</citation>
    <PMID>27629148</PMID>
  </results_reference>
  <results_reference>
    <citation>Novo Nordisk. (2015). TRESIBA® (insulin degludec injection) Label. 28-29</citation>
  </results_reference>
  <results_reference>
    <citation>Novo Nordisk. (2000). NovoLog (insulin aspart [rDNA origin]) injection label. 21-22</citation>
  </results_reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 30, 2018</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>February 23, 2021</last_update_submitted>
  <last_update_submitted_qc>February 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Continuous Glucose Monitoring</keyword>
  <keyword>CGM</keyword>
  <keyword>Continuous Subcutaneous Insulin Infusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data and statistical analysis will be available to any researcher with appropriate request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>post study, up to 5 years</ipd_time_frame>
    <ipd_access_criteria>email principal investigator</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT04409587/Prot_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/NCT04409587
org study id: MDEC2018
nct id: NCT04409587
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this investigator-initiated trial is to compare the effect of a daily
      injection of insulin degludec vs. basal insulin delivery via Continuous Subcutaneous Insulin
      Infusion (CSII), both in combination with bolus insulin delivery via the patient's usual
      insulin pump with insulin aspart, on glycemic variability, overall blood glucose control and
      incidence of hypoglycemia, all assessed by continuous glucose monitor (CGM), as well as
      patient satisfaction, in patients with type 1 diabetes currently using CSII.
The primary objective of this trial is to determine whether insulin degludec will provide an
      equally stable and consistent basal glycemic profile with lower glycemic variability as
      determined by Continuous Glucose Monitoring compared to insulin aspart delivered by
      Continuous Subcutaneous Insulin Infusion in patients with type 1 diabetes experienced in use
      of insulin pump therapy. Specifically, this study will determine if the percent time in the
      target glycemic range (70 to 180 mg/dl) by Continuous Glucose Monitoring is superior using
      insulin degludec than continuously infused insulin aspart, and if degludec is associated with
      lower glucose variability as assessed by the standard deviation (SD) of the mean daily
      glucose by Continuous Glucose Monitoring. Particular attention will be given to the nocturnal
      glucose profile (from midnight to 6 am) which most closely reflects basal insulin action as
      it is typically the time of day least affected by bolus insulin, food intake or exercise.
      Quality of life questionnaires regarding treatment preference will be used to capture patient
      preference for method of basal insulin delivery.

      RESEARCH DESIGN AND METHODS

      Study hypothesis:

      It is anticipated, based on the low glycemic variability of insulin degludec shown in glucose
      clamp studies and seen in clinical practice, that insulin degludec will provide more stable
      24 hour basal insulin action than insulin aspart by Continuous Subcutaneous Insulin Infusion
      (CSII) in patients with type 1 diabetes.

      Primary endpoint:

      Percent time in euglycemia (BG 70 to 180 mg/dl) by Continuous Glucose Monitoring (CGM) during
      the final 14 days of each treatment period during steady state (with basal insulin delivery
      as either one daily injection of insulin degludec or as insulin aspart via CSII).

      Study type:

      This will be a randomized, cross-over, open label, single-center study consisting of a 20
      week period on each of two basal insulin delivery methods, both in combination with insulin
      aspart with boluses taken by insulin pump. Each 20 week period will consist of a 4 week
      insulin optimization period for titration of basal and bolus insulin doses, followed by a 16
      week maintenance period. The final 2 weeks of the maintenance period during each treatment
      arm will be used for endpoint data collection. The treatment sequence will occur in random
      order. The study population will include patients with type 1 diabetes with good baseline
      glycemic control who are experienced in the use of both CSII and CGM; the cross-over design
      allows each subject to serve as his or her own control.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This will be a randomized, cross-over, open label, single-center study consisting of a 20 week period on each of two basal insulin delivery methods, both in combination with insulin aspart with boluses taken by insulin pump. Each 20 week period will consist of a 4 week insulin optimization period for titration of basal and bolus insulin doses, followed by a 16 week maintenance period. The final 2 weeks of the maintenance period during each treatment arm will be used for endpoint data collection. The treatment sequence will occur in random order. The study population will include patients with type 1 diabetes with good baseline glycemic control who are experienced in the use of both Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitor; the cross-over design allows each subject to serve as his or her own control.
primary purpose: Treatment
masking: None (Open Label)
masking description: This is an unblinded study as the two basal insulin delivery methods (degludec via injection vs. aspart via CSII) cannot be blinded. One group of patients will first use degludec for 20 weeks then switch to CSII for 20 weeks. As all eligible patients who sign the IRB consent form are identified, a random number will be generated to determine the treatment with which they begin first. The other group of patients will start with CSII and after 20 weeks switch to Tresiba for 20 weeks. Randomization sequence will be determined by computerized randomization program. All patients will receive both treatments unless they drop out. Dropouts are unlikely since the participants are all regular continuing patients of the site's clinical practice.
measure: Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM
time frame: 46 weeks
description: Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM during the final 14 days of each treatment period during steady state (with basal insulin delivery as either one daily injection of insulin degludec or as insulin aspart via CSII)
measure: Standard Deviation (SD) of blood glucose by CGM for two week period
time frame: 46 weeks
description: SD of interstitial fluid glucose by CGM for 2 week period during each basal insulin delivery method. (Note: because the Dexcom Platinum G5 CGM is currently only FDA approved for 7 days of use, two contiguous CGM periods using 2 sensors, each for 7 days, will be performed to capture 2 weeks of continuous CGM data.) Dexcom G6 is approved by FDA for 10 days of use so 2 sensors will be used during the CGM periods.
measure: SD of blood glucose by CGM during the nocturnal period
time frame: 46 weeks
description: SD of blood glucose by CGM during the nocturnal period (midnight to 6 am) during each basal insulin delivery method
measure: Percent time in hypoglycemia by CGM
time frame: 46 weeks
description: Percent time in hypoglycemia by CGM, captured at 2 levels of hypoglycemia: BG < 54 mg/dl (level 2) and BG 55-69 mg/dl (level 1), for each basal insulin treatment.
measure: Percent time in normoglycemia
time frame: 46 weeks
description: Percent time in normoglycemia (BG 70 to 140 mg/dl) by CGM during each basal treatment period.
measure: Time to recovery from level 2 hypoglycemia
time frame: 46 weeks
description: Time to recovery from level 2 hypoglycemia (BG >70 with resolution of symptoms) on each treatment. If a second event (BG < 70 mg/dl) occurs within 60 minutes of a previous hypoglycemic event, this will be considered part of the same hypoglycemic episode.
measure: Patient satisfaction
time frame: 46 weeks
description: Patient satisfaction by TRIM-D questionnaires with each basal insulin treatment.
measure: Patient satisfaction
time frame: 46 weeks
description: Patient satisfaction by TRIM-DD questionnaires with each basal insulin treatment.
measure: HbA1c
time frame: 46 weeks
description: HbA1c after 20 weeks of each basal insulin treatment.
measure: Total daily insulin dosage
time frame: 46 weeks
description: Total daily insulin dose, total basal insulin dose, and total bolus insulin dose on each treatment.
arm group label: NovoLog®-only
arm group type: No Intervention
description: In the aspart-Only group, the subject will only take aspart through the their pump. This study population will have an established expertise in diabetes self-management with previous knowledge of insulin pump therapy and Dexcom Continuous Glucose Monitoring (CGM). Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses. Aspart is put into their pump and delivered to their body through a small tube placed under your skin. In this NovoLog®-only treatment group, the subject will take aspart with each meal while your pump also gives you a slow, continuous dose of aspart for basal insulin. This treatment group is very similar (or even identical) to the treatment the subject was receiving prior to starting the study.
arm group label: Novolog® and Tresiba® Group
arm group type: Active Comparator
description: This study population will have an expertise in diabetes self-management with their insulin pump and Dexcom CGM. In the Novolog® and Tresiba® group, the subject will still take aspart via their pump for meals and correction boluses, but they will reduce the slow trickle (basal insulin) programmed in their pump to almost zero. Instead of receiving their normal basal insulin via CSII, the subject will injected degludec once or twice daily from an insulin pen for your basal insulin.
intervention type: Drug
intervention name: Aspart
description: A population of well controlled patients with type 1 diabetes who are experienced in the use of both Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitor (CGM) was chosen in order to assess the effect of the change in glycemic profile using two different methods of basal insulin delivery. Allowing the subjects to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the chances of skipping meal boluses and correction doses.
Replacing basal insulin delivery by CSII with a single daily injection of degludec will add minimal, if any, treatment burden which will be offset by potential therapeutic benefits. These benefits include the potential for reduced glycemic variability and the elimination of the risk of hyperglycemia and DKA with basal insulin interruption which can occur with infusion set occlusion or disgorging inherent to Continuous Subcutaneous Insulin Infusion.
arm group label: Novolog® and Tresiba® Group
other name: Degludec
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
url: http://online.liebertpub.com/doi/full/10.1089/DIA.2017.0175
description: Hauzenber JR et al. Diab Technol Therapeutics 2017
citation: Misso ML, Egberts KJ, Page M, O'Connor D, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD005103. doi: 10.1002/14651858.CD005103.pub2.
PMID: 20091571
citation: Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, Maahs DM, Tamborlane WV; T1D Exchange Clinic Network. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015 Jun;38(6):971-8. doi: 10.2337/dc15-0078.
PMID: 25998289
citation: Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012 Sep;14(9):859-64. doi: 10.1111/j.1463-1326.2012.01627.x. Epub 2012 Jun 7.
PMID: 22594461
citation: Lane W, Bailey TS, Gerety G, Gumprecht J, Philis-Tsimikas A, Hansen CT, Nielsen TSS, Warren M; Group Information; SWITCH 1. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):33-44. doi: 10.1001/jama.2017.7115.
PMID: 28672316
citation: Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available.
PMID: 27629148
citation: Novo Nordisk. (2015). TRESIBA® (insulin degludec injection) Label. 28-29
citation: Novo Nordisk. (2000). NovoLog (insulin aspart [rDNA origin]) injection label. 21-22
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1
sharing ipd: Yes
ipd description: Data and statistical analysis will be available to any researcher with appropriate request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: post study, up to 5 years
ipd access criteria: email principal investigator
provided document: 