<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/NCT04450563</url>
  </required_header>
  <id_info>
    <org_study_id>2021 - 6542</org_study_id>
    <nct_id>NCT04450563</nct_id>
  </id_info>
  <brief_title>Low Dose Empagliflozin in Adults With Type 1 Diabetes on Closed Loop Insulin System</brief_title>
  <acronym>CL-LoDE</acronym>
  <official_title>The Effect of Low-dose Empagliflozin on Glucose Control in Adult Patients With Type 1 Diabetes on a Closed-loop Insulin System: a Randomized Cross-over Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University</source>
  <oversight_info>
    <has_dmc>No</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>
      A closed-loop insulin system, also referred to as the &quot;artificial pancreas&quot; (AP), is made up&#xD;
      of an insulin pump, a continuous glucose monitor, and an application communicating between&#xD;
      the two to adjust insulin administration based on glucose control. This is meant for the&#xD;
      treatment of type 1 diabetes. The McGill Artificial Pancreas (MAP) has been used previously&#xD;
      in type 1 diabetes with significant benefits. Though prior studies have shown significant&#xD;
      benefit with this system, some challenges still exist.&#xD;
&#xD;
      Empagliflozin is used in type 2 diabetes; it allows for glucose to be removed through the&#xD;
      urine. Though its use is not approved in type 1 diabetes in North America, it (along with&#xD;
      similar drugs) has been used in studies as adjunctive therapy with insulin with benefits on&#xD;
      blood sugar control.&#xD;
&#xD;
      The purpose of our study is to see if a small dose of empagliflozin (2.5 mg and 5 mg) is&#xD;
      enough to help those who cannot achieve adequate glucose control on a closed-loop insulin&#xD;
      system.&#xD;
&#xD;
      The primary hypotheses of the study are the following:&#xD;
&#xD;
        1. The use of empagliflozin 2.5 mg daily will increase time in range compared to placebo&#xD;
           for those on the closed-loop system.&#xD;
&#xD;
        2. The use of empagliflozin 5 mg daily will increase time in range compared to placebo for&#xD;
           those on the closed-loop system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Some of the novel advances for type 1 diabetes treatment include continuous subcutaneous&#xD;
      insulin pump therapy (CSII) and continuous glucose monitoring (CGM). A step further is the&#xD;
      combination of both technologies, i.e. closed-loop insulin system, also referred to as the&#xD;
      &quot;artificial pancreas&quot; (AP), where insulin delivery is modified based on glucose readings from&#xD;
      CGM. Multiple studies have shown the benefit of closed-loop insulin systems on glycemic&#xD;
      control, with their strength being nocturnal euglycemia, while post-prandial hyperglycemia&#xD;
      remains a challenge due to decreased insulin absorption.&#xD;
&#xD;
      Novel medication therapies previously used for type 2 diabetes are also under investigation&#xD;
      for type 1 diabetes. Sodium glucose-linked cotransporter inhibitors (SGLT2i's) increase&#xD;
      urinary glucose excretion and, in doing so, euglycemia. Their use is predominantly in type 2&#xD;
      diabetes for glucose control and for cardiovascular and renal protection, though various&#xD;
      studies have demonstrated improved glycemic control with SGLT2i use as adjunct to insulin&#xD;
      therapy in the treatment of type 1 diabetes. The use of both closed-loop insulin therapy in&#xD;
      conjunction with SGLT2i therapy is thus a novel treatment for optimizing glycemic control in&#xD;
      type 1 diabetes, in particular those who do not yet reach target glucose levels despite being&#xD;
      on a closed-loop system. Our research group has previously studied the impact of a hybrid&#xD;
      closed-loop insulin system with empagliflozin 25 mg, which increased the time in target&#xD;
      glucose range of 3.9 to 10.0 from 70% to 84%. Notably, the EASE-3 (Empagliflozin as&#xD;
      Adjunctive to inSulin thErapy) trial had previously shown a beneficial glucose effect with&#xD;
      empagliflozin 2.5 mg without increasing the risk of diabetic ketoacidosis.&#xD;
&#xD;
      The objective of the study is to assess the effectiveness of low-dose empagliflozin (2.5 mg&#xD;
      and 5 mg) on glucose control in adult patients with type 1 diabetes on a closed-loop insulin&#xD;
      pump system, who would not otherwise be within a percentage of time in range (TIR) by blood&#xD;
      glucose of 3.9 to 10 mmol/L of &gt; 70% on the system.&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      The primary hypotheses of the study are the following:&#xD;
&#xD;
        1. The use of empagliflozin 2.5 mg daily will increase time in range compared to placebo&#xD;
           for those on the closed-loop system.&#xD;
&#xD;
        2. The use of empagliflozin 5 mg daily will increase time in range compared to placebo for&#xD;
           those on the closed-loop system.&#xD;
&#xD;
      There will also be secondary hypotheses, based on quality of life measures, the effect of&#xD;
      both doses of empagliflozin on time spent in various ranges of blood glucose, average total&#xD;
      daily insulin dose, and average change in ketone levels. It is hypothesized that either dose&#xD;
      will increase the time spent in a favourable glucose range, with less time spent hypo- and&#xD;
      hyper-glycemic, with improved quality of life measures and lower total daily doses of insulin&#xD;
      without increase in ketone levels.&#xD;
&#xD;
      Methods This is a three-way, randomized, cross-over double-blinded outpatient trial to&#xD;
      compare the effect of glycemic control for adult participants with type 1 diabetes taking&#xD;
      placebo, empagliflozin 2.5 mg daily, and empagliflozin 5 mg daily while using a hybrid&#xD;
      closed-loop insulin system (i.e. the McGill Artificial Pancreas (MAP), used in over 20&#xD;
      studies thus far). Adult participants meeting inclusion criteria after baseline laboratory&#xD;
      investigations and training will use the MAP during a run-in period of 14 days to identify&#xD;
      those with TIR &lt; 70%. The chosen participants will have a randomized sequence of&#xD;
      interventions (placebo, empagliflozin 2.5 mg, or 5 mg), each intervention lasting 14 days,&#xD;
      with a washout period of 7 - 21 days in between. Optimization of MAP insulin parameters will&#xD;
      be adjusted on approximately Day 4 so that the last 10 days of CGM with each intervention&#xD;
      will be used for data analysis. During each intervention, ketone levels will be measured&#xD;
      daily. Questionnaires assessing quality of life will be filled out after each intervention.&#xD;
      There will be a visit at the end of the study to assess participant satisfaction. Data&#xD;
      analysis will be conducted to compare the differences in each intervention for each&#xD;
      participant of the following : CGM data of the last 10 days of each intervention, daily&#xD;
      ketone levels, total daily dose of insulin, and scores of quality of life questionnaires.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2020</start_date>
  <completion_date type="Actual">January 13, 2022</completion_date>
  <primary_completion_date type="Actual">January 5, 2022</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of time of plasma glucose levels spent in target range (placebo vs empagliflozin 2.5 mg)</measure>
    <time_frame>10 days</time_frame>
    <description>Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs. empagliflozin 2.5 mg ono closed-loop insulin system.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of time of plasma glucose levels spent in target range (placebo vs empagliflozin 5 mg)</measure>
    <time_frame>10 days</time_frame>
    <description>Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs. empagliflozin 5 mg ono closed-loop insulin system.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of time spent in the following ranges of glucose levels between 3.9 and 7.8 mmol/L</measure>
    <time_frame>10 days (for each intervention)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of time spent in the following ranges of glucose levels: below 3.9, 3.3 and 2.8 mmol/L</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, 13.9, and 16.7 mmol/L</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average glucose level</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage coefficient of variation of glucose levels</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measure by Type 1 Diabetes Distress Scale: score is the average of 28 items from 1 to 6 (higher score indicates more emotional distress)</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measure by Hypoglycemic Fear Survey - II: score is the average of 33 items from 1 to 5 (average of higher scorer equates to more distress)</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measure by INSPIRE (Insulin delivery Systems: Perceptions, Ideas, Reflections and Expectations) questionnaire for adults: score is the average of 22 items from 1 to 5 (average of higher scorer equates to more distress)</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily insulin dose</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average point-of-care ketone level per intervention</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rise in ketone level between interventions</measure>
    <time_frame>10 days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Placebo + closed-loop insulin system</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Empagliflozin 2.5 mg + closed-loop insulin system</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Empagliflozin 5 mg + closed-loop insulin system</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>14-day outpatient intervention</intervention_name>
    <description>The patient will be on the closed-loop insulin system and the intervention drug (placebo, empagliflozin 2.5 mg, or empagliflozin 5 mg) for 14 days. Insulin reductions will be made to avoid hypoglycemia with the drug agent. Remote contact around Day 4 (+/- 2 days) will be made to optimize insulin settings. The last 10 days will be used to assess continuous glucose monitoring data during each intervention. A wash-out period of 7 - 21 days will separate each intervention.</description>
    <arm_group_label>Empagliflozin 2.5 mg + closed-loop insulin system</arm_group_label>
    <arm_group_label>Empagliflozin 5 mg + closed-loop insulin system</arm_group_label>
    <arm_group_label>Placebo + closed-loop insulin system</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A clinical diagnosis of type 1 diabetes for at least one year, as per their treating&#xD;
             diabetes physician in agreement with the primary investigator's clinical judgment&#xD;
             (confirmatory C-peptide and antibodies will not be required)&#xD;
&#xD;
          -  HbA1c between 7 and 10.5% (both extremes inclusive), performed within the last 6&#xD;
             months prior to study inclusion&#xD;
&#xD;
          -  Insulin pump use (of any modality) for minimum 3 months&#xD;
&#xD;
          -  Agreement to the use of highly effective method of birth control in women of&#xD;
             child-bearing age and active avoidance of pregnancy during the trial. Child-bearing&#xD;
             potential refers to participants of the female sex post-menarche and have not reached&#xD;
             menopause or have a disclosed medical condition causing sterility (e.g. hysterectomy).&#xD;
             Post-menopausal state refers to the absence of menses for 12 months without any&#xD;
             alternative cause.&#xD;
&#xD;
          -  Time in range (3.9 - 10.0 mmol/L) &lt; 70% as per CGM readings of the last 10 days during&#xD;
             a 2-week run-in period on the closed-loop insulin delivery system.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or &lt; 2 week use of any other anti-hyperglycemic agent other than insulin&#xD;
&#xD;
          -  Current or &lt;/= 1 month use of supra-physiological doses of oral glucocorticoids&#xD;
&#xD;
          -  Requirement for regular use of acetaminophen (which may decrease CGM fidelity)&#xD;
&#xD;
          -  Planned or ongoing pregnancy&#xD;
&#xD;
          -  Breastfeeding individuals&#xD;
&#xD;
          -  Severe hypoglycemic episode within the last 3 months, defined as an event where&#xD;
             glucose was &lt; 4 mmol/L resulting in seizure, loss of consciousness, or need to present&#xD;
             to the emergency department&#xD;
&#xD;
          -  Severe diabetic ketoacidosis within the last 3 years (&quot;severe&quot; referring to need to&#xD;
             present to medical attention and requirement of intravenous insulin)&#xD;
&#xD;
          -  Active infection of any kind at the time of study enrolment, or any active foot ulcer&#xD;
&#xD;
          -  Recurrent infections (i.e. more than 2 in 1 year) of the following: genital, urinary&#xD;
             tract infections, soft tissue, joint, or bone&#xD;
&#xD;
          -  Known severe peripheral vascular disease including the following: symptomatic&#xD;
             claudication, loss of peripheral pulses, signs of peripheral arterial insufficiency as&#xD;
             per initial clinical exam, previously documented insufficiency as per ankle or toe&#xD;
             brachial index, prior amputations due to peripheral vascular disease&#xD;
&#xD;
          -  Osteoporosis defined as prior fragility fracture, previously measured bone mineral&#xD;
             density with T or Z score &lt; -2.5, or need for anti-osteoporotic medications&#xD;
&#xD;
          -  Glomerular filtration rate less than 30 mL/minutes/1.73 m2 as per CKD-EPI (Chronic&#xD;
             Kidney Disease Epidemiology Collaboration) equation.&#xD;
&#xD;
          -  Any serious medical or psychiatric illness likely to interfere with study&#xD;
             participation as per the judgment of the investigator (e.g. cirrhosis, active cancer,&#xD;
             decompensated schizophrenia)&#xD;
&#xD;
          -  Prior adverse reaction to SGLT2 inhibitors (e.g. empagliflozin, dapagliflozin)&#xD;
&#xD;
          -  Inability to travel to the research center within 3 hours if needed during the study&#xD;
             interventions&#xD;
&#xD;
          -  Failure to comply to the study protocol and/or research group's recommendations (e.g.&#xD;
             change in pump parameters, ketone measurement)&#xD;
&#xD;
          -  Inability or unwillingness to comply to safe diabetes management in the view of the&#xD;
             study group (e.g. inappropriate treatment of hypoglycemia or lack thereof)&#xD;
&#xD;
          -  Anticipation of a significant change in exercise regimen between initiation of the&#xD;
             intervention blocks (i.e. starting or stopping an organized sport)&#xD;
&#xD;
          -  Any demonstrate of difficulty in using the McGill Artificial Pancreas system following&#xD;
             training, as per investigator's judgment&#xD;
&#xD;
          -  Concern for safety of the participant, as per the clinical judgment of the primary&#xD;
             investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmad Haidar, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Tsoukas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melissa-Rosina Pasqua, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinique Médicale Hygea</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3T2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>October 6, 2022</last_update_submitted>
  <last_update_submitted_qc>October 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes mellitus, type 1</keyword>
  <keyword>Artificial pancreas</keyword>
  <keyword>Closed-loop system</keyword>
  <keyword>Insulin</keyword>
  <keyword>Empagliflozin</keyword>
  <keyword>SGLT2 inhibitor</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 17, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT04450563/Prot_SAP_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/NCT04450563
org study id: 2021 - 6542
nct id: NCT04450563
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A closed-loop insulin system, also referred to as the "artificial pancreas" (AP), is made up
      of an insulin pump, a continuous glucose monitor, and an application communicating between
      the two to adjust insulin administration based on glucose control. This is meant for the
      treatment of type 1 diabetes. The McGill Artificial Pancreas (MAP) has been used previously
      in type 1 diabetes with significant benefits. Though prior studies have shown significant
      benefit with this system, some challenges still exist.

      Empagliflozin is used in type 2 diabetes; it allows for glucose to be removed through the
      urine. Though its use is not approved in type 1 diabetes in North America, it (along with
      similar drugs) has been used in studies as adjunctive therapy with insulin with benefits on
      blood sugar control.

      The purpose of our study is to see if a small dose of empagliflozin (2.5 mg and 5 mg) is
      enough to help those who cannot achieve adequate glucose control on a closed-loop insulin
      system.

      The primary hypotheses of the study are the following:

        1. The use of empagliflozin 2.5 mg daily will increase time in range compared to placebo
           for those on the closed-loop system.

        2. The use of empagliflozin 5 mg daily will increase time in range compared to placebo for
           those on the closed-loop system.
Some of the novel advances for type 1 diabetes treatment include continuous subcutaneous
      insulin pump therapy (CSII) and continuous glucose monitoring (CGM). A step further is the
      combination of both technologies, i.e. closed-loop insulin system, also referred to as the
      "artificial pancreas" (AP), where insulin delivery is modified based on glucose readings from
      CGM. Multiple studies have shown the benefit of closed-loop insulin systems on glycemic
      control, with their strength being nocturnal euglycemia, while post-prandial hyperglycemia
      remains a challenge due to decreased insulin absorption.

      Novel medication therapies previously used for type 2 diabetes are also under investigation
      for type 1 diabetes. Sodium glucose-linked cotransporter inhibitors (SGLT2i's) increase
      urinary glucose excretion and, in doing so, euglycemia. Their use is predominantly in type 2
      diabetes for glucose control and for cardiovascular and renal protection, though various
      studies have demonstrated improved glycemic control with SGLT2i use as adjunct to insulin
      therapy in the treatment of type 1 diabetes. The use of both closed-loop insulin therapy in
      conjunction with SGLT2i therapy is thus a novel treatment for optimizing glycemic control in
      type 1 diabetes, in particular those who do not yet reach target glucose levels despite being
      on a closed-loop system. Our research group has previously studied the impact of a hybrid
      closed-loop insulin system with empagliflozin 25 mg, which increased the time in target
      glucose range of 3.9 to 10.0 from 70% to 84%. Notably, the EASE-3 (Empagliflozin as
      Adjunctive to inSulin thErapy) trial had previously shown a beneficial glucose effect with
      empagliflozin 2.5 mg without increasing the risk of diabetic ketoacidosis.

      The objective of the study is to assess the effectiveness of low-dose empagliflozin (2.5 mg
      and 5 mg) on glucose control in adult patients with type 1 diabetes on a closed-loop insulin
      pump system, who would not otherwise be within a percentage of time in range (TIR) by blood
      glucose of 3.9 to 10 mmol/L of > 70% on the system.

      Hypothesis

      The primary hypotheses of the study are the following:

        1. The use of empagliflozin 2.5 mg daily will increase time in range compared to placebo
           for those on the closed-loop system.

        2. The use of empagliflozin 5 mg daily will increase time in range compared to placebo for
           those on the closed-loop system.

      There will also be secondary hypotheses, based on quality of life measures, the effect of
      both doses of empagliflozin on time spent in various ranges of blood glucose, average total
      daily insulin dose, and average change in ketone levels. It is hypothesized that either dose
      will increase the time spent in a favourable glucose range, with less time spent hypo- and
      hyper-glycemic, with improved quality of life measures and lower total daily doses of insulin
      without increase in ketone levels.

      Methods This is a three-way, randomized, cross-over double-blinded outpatient trial to
      compare the effect of glycemic control for adult participants with type 1 diabetes taking
      placebo, empagliflozin 2.5 mg daily, and empagliflozin 5 mg daily while using a hybrid
      closed-loop insulin system (i.e. the McGill Artificial Pancreas (MAP), used in over 20
      studies thus far). Adult participants meeting inclusion criteria after baseline laboratory
      investigations and training will use the MAP during a run-in period of 14 days to identify
      those with TIR < 70%. The chosen participants will have a randomized sequence of
      interventions (placebo, empagliflozin 2.5 mg, or 5 mg), each intervention lasting 14 days,
      with a washout period of 7 - 21 days in between. Optimization of MAP insulin parameters will
      be adjusted on approximately Day 4 so that the last 10 days of CGM with each intervention
      will be used for data analysis. During each intervention, ketone levels will be measured
      daily. Questionnaires assessing quality of life will be filled out after each intervention.
      There will be a visit at the end of the study to assess participant satisfaction. Data
      analysis will be conducted to compare the differences in each intervention for each
      participant of the following : CGM data of the last 10 days of each intervention, daily
      ketone levels, total daily dose of insulin, and scores of quality of life questionnaires.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Percentage of time of plasma glucose levels spent in target range (placebo vs empagliflozin 2.5 mg)
time frame: 10 days
description: Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs. empagliflozin 2.5 mg ono closed-loop insulin system.
measure: Percentage of time of plasma glucose levels spent in target range (placebo vs empagliflozin 5 mg)
time frame: 10 days
description: Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs. empagliflozin 5 mg ono closed-loop insulin system.
measure: Percentage of time spent in the following ranges of glucose levels between 3.9 and 7.8 mmol/L
time frame: 10 days (for each intervention)
measure: Percentage of time spent in the following ranges of glucose levels: below 3.9, 3.3 and 2.8 mmol/L
time frame: 10 days
measure: Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, 13.9, and 16.7 mmol/L
time frame: 10 days
measure: Average glucose level
time frame: 10 days
measure: Percentage coefficient of variation of glucose levels
time frame: 10 days
measure: Quality of life measure by Type 1 Diabetes Distress Scale: score is the average of 28 items from 1 to 6 (higher score indicates more emotional distress)
time frame: 10 days
measure: Quality of life measure by Hypoglycemic Fear Survey - II: score is the average of 33 items from 1 to 5 (average of higher scorer equates to more distress)
time frame: 10 days
measure: Quality of life measure by INSPIRE (Insulin delivery Systems: Perceptions, Ideas, Reflections and Expectations) questionnaire for adults: score is the average of 22 items from 1 to 5 (average of higher scorer equates to more distress)
time frame: 10 days
measure: Total daily insulin dose
time frame: 10 days
measure: Average point-of-care ketone level per intervention
time frame: 10 days
measure: Rise in ketone level between interventions
time frame: 10 days
arm group label: Placebo + closed-loop insulin system
arm group type: Active Comparator
arm group label: Empagliflozin 2.5 mg + closed-loop insulin system
arm group type: Experimental
arm group label: Empagliflozin 5 mg + closed-loop insulin system
arm group type: Experimental
intervention type: Drug
intervention name: 14-day outpatient intervention
description: The patient will be on the closed-loop insulin system and the intervention drug (placebo, empagliflozin 2.5 mg, or empagliflozin 5 mg) for 14 days. Insulin reductions will be made to avoid hypoglycemia with the drug agent. Remote contact around Day 4 (+/- 2 days) will be made to optimize insulin settings. The last 10 days will be used to assess continuous glucose monitoring data during each intervention. A wash-out period of 7 - 21 days will separate each intervention.
arm group label: Empagliflozin 2.5 mg + closed-loop insulin system
arm group label: Empagliflozin 5 mg + closed-loop insulin system
arm group label: Placebo + closed-loop insulin system
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ahmad Haidar, PhD
role: Study Chair
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Michael Tsoukas, MD
role: Principal Investigator
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Melissa-Rosina Pasqua, MD
role: Principal Investigator
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
sharing ipd: Undecided
provided document: 