xml: <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/NCT06021145</url>
    </required_header>
    <id_info>
      <org_study_id>2024-9953</org_study_id>
      <nct_id>NCT06021145</nct_id>
    </id_info>
    <brief_title>Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes</brief_title>
    <official_title>Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes: a Randomized Controlled Parallel Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Diabetes Canada</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this 26-week multicenter, randomized, parallel, placebo-controlled trial is to&#xD;
        test the effectiveness of empagliflozin use in conjunction with automated insulin delivery&#xD;
        (AID) to improve glucose control in individuals with type 1 diabetes who do not meet target&#xD;
        recommendations for time in range (3.9-10.0 mmol/L). The main question it aims to answer is:&#xD;
  &#xD;
        - Will use of empagliflozin (2.5 mg/day) increase time spent in the target range of 3.9 to&#xD;
        10.0 mmol/L compared to placebo for individuals on an AID system who do not meet glycemic&#xD;
        targets?&#xD;
  &#xD;
        Participants will either take 2.5 mg of empagliflozin or a placebo daily for 26 weeks while&#xD;
        remaining on their current AID system.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2024</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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo)</measure>
      <time_frame>4 weeks</time_frame>
      <description>Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on an automated insulin delivery system vs empagliflozin (2.5 mg) on an automated insulin delivery system. Percent measured as per continuous glucose monitor (CGM) data.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L</measure>
      <time_frame>4 weeks</time_frame>
      <description>Percent as per CGM data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L</measure>
      <time_frame>4 weeks</time_frame>
      <description>Percent as per CGM data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L</measure>
      <time_frame>4 weeks</time_frame>
      <description>Percent as per CGM data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean glucose levels</measure>
      <time_frame>4 weeks</time_frame>
      <description>Defined as per CGM data, in mmol/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Standard deviation of glucose levels</measure>
      <time_frame>4 weeks</time_frame>
      <description>Defined as per CGM data, in mmol/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Coefficient of variance of glucose levels</measure>
      <time_frame>4 weeks</time_frame>
      <description>Percent as per CGM data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total insulin delivery (overall, basal, and bolus)</measure>
      <time_frame>4 weeks</time_frame>
      <description>Defined as per participant's pump data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean daily carbohydrate intake</measure>
      <time_frame>4 weeks</time_frame>
      <description>Defined as per participant's pump data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>HbA1c</measure>
      <time_frame>26 weeks</time_frame>
      <description>Percent as per blood test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Estimated glomerular filtration rate (eGFR)</measure>
      <time_frame>26 weeks</time_frame>
      <description>mL/min/1.73 m^2 as per blood test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Lipid profile</measure>
      <time_frame>26 weeks</time_frame>
      <description>Includes measurements in mmol/L as per blood test: total cholesterol, triglycerides, HDL-C, LDL-C, nonHDL-C</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Brain Natriuretic Peptide (NT-pro-BNP)</measure>
      <time_frame>26 weeks</time_frame>
      <description>ng/L as per blood test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Liver profile - bilirubin</measure>
      <time_frame>26 weeks</time_frame>
      <description>umol/L as per blood test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP)</measure>
      <time_frame>26 weeks</time_frame>
      <description>U/L as per blood test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurement of body mass: weight and height</measure>
      <time_frame>26 weeks</time_frame>
      <description>Body measurement as described (weight in kilograms and height in meters). Weight and height will be combined to report body mass index in kg/m^2.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Waist and hip circumference, and waist-to-hip ratio</measure>
      <time_frame>26 weeks</time_frame>
      <description>Body measurements as described (waist and hip circumference in centimeters). Waist and hip cirumference will be combined to report waist-to-hip ratio.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart rate</measure>
      <time_frame>26 weeks</time_frame>
      <description>Body measurement as described (beats per minutes)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood pressure</measure>
      <time_frame>26 weeks</time_frame>
      <description>Body measurement as described (diastolic and systolic pressure; mmHg)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire</measure>
      <time_frame>26 weeks</time_frame>
      <description>Self-report scale (1 min = &quot;not a problem&quot; to 6 max = &quot;a very serious problem&quot;) that assesses a participant's distress surrounding their diabetes with higher scores correlating to higher distress.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average scores between interventions based on Hypoglycemic Fear Survey - II</measure>
      <time_frame>26 weeks</time_frame>
      <description>Likert scale (1 min to 5 max) that assesses a participant's worry surrounding hypoglycemia with higher scores indicating increased fear of hypoglycemia.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire</measure>
      <time_frame>26 weeks</time_frame>
      <description>Self-report scale (0 min = &quot;very dissatisfied&quot; to 6 max = &quot;very satisfied&quot;) that assesses a participant's satisfaction surrounding the treatment for their diabetes with higher scores indicating greater satisfaction with treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fasting ketone levels</measure>
      <time_frame>7 days</time_frame>
      <description>As per ketone test strip and meter; measured by participant</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">46</enrollment>
    <condition>Type 1 Diabetes</condition>
    <arm_group>
      <arm_group_label>Empagliflozin 2.5 mg daily</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Empagliflozin is a sodium/glucose cotransporter 2 inhibitor (SGLT2i) that inhibits glucose reabsorption in the kidney. In this study, a capsule of empagliflozin 2.5 mg will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>As a control, a placebo capsule will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Empagliflozin</intervention_name>
      <description>26-week use of automated insulin delivery system with empagliflozin (2.5 mg daily) in individuals with suboptimal time in range.</description>
      <arm_group_label>Empagliflozin 2.5 mg daily</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>26-week use of automated insulin delivery system with placebo (daily) in individuals with suboptimal time in range.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Individuals ≥ 18 years of age.&#xD;
  &#xD;
            -  A clinical diagnosis of type 1 diabetes for at least one year, as per the&#xD;
               investigators' clinical judgment (confirmatory C-peptide and antibodies will not be&#xD;
               required).&#xD;
  &#xD;
            -  Minimum 3-month use of a commercial advanced AID system.&#xD;
  &#xD;
            -  Time in range (3.9 to 10.0 mmol/L) &lt; 70% on their personal AID system in the 30 days&#xD;
               prior to screening (with minimum 70% time spent in closed-loop mode).&#xD;
  &#xD;
            -  Agreement to use a highly effective method of birth control for individuals 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 who have not reached&#xD;
               menopause and who do not have a disclosed medical condition causing sterility (ex:&#xD;
               hysterectomy). Post-menopausal state refers to the absence of menses for 12 months&#xD;
               without any alternative cause.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current or ≤ 2 week use of any anti-hyperglycemic agent other than insulin (such as&#xD;
               SGTL2i).&#xD;
  &#xD;
            -  Current or ≤ 1 month use of Glucagon-like Peptide 1 (GLP1)-Receptor Agonists.&#xD;
  &#xD;
            -  Current or ≤ 1 month use of supraphysiological doses of oral or intravenous&#xD;
               glucocorticoids.&#xD;
  &#xD;
            -  Planned or ongoing very low carbohydrate diet (&lt; 50g/day).&#xD;
  &#xD;
            -  Glomerular filtration rate (eGFR) &lt; 30 mL/min/1.73 m2 as per CKD-EPI formula with&#xD;
               creatinine levels measured within the last 12 months.&#xD;
  &#xD;
            -  Use of hydroxyurea.&#xD;
  &#xD;
            -  Planned or ongoing pregnancy.&#xD;
  &#xD;
            -  Breastfeeding.&#xD;
  &#xD;
            -  Ongoing active risk of recurrent genito-urinary infections, as per the clinical&#xD;
               judgement of the investigators.&#xD;
  &#xD;
            -  Severe hypoglycemic episode within 1 month of screening, defined as an event resulting&#xD;
               in seizure, loss of consciousness, or need to present to the emergency department.&#xD;
  &#xD;
            -  Diabetic ketoacidosis within 6 months of screening, defined as an event requiring the&#xD;
               need to present to medical attention and administration of intravenous insulin.&#xD;
  &#xD;
            -  Any serious medical illness likely to interfere with the ability to complete the trial&#xD;
               per the judgment of the investigators.&#xD;
  &#xD;
            -  Clinically significant retinopathy as judged by the investigator.&#xD;
  &#xD;
            -  Recent (&lt; 3 months) acute macrovascular event (ex: acute coronary syndrome or cardiac&#xD;
               surgery).&#xD;
  &#xD;
            -  Prior serious reaction to SGLT2i.&#xD;
  &#xD;
            -  Use of the Medtronic 670G or 770G system in the last 30 days.&#xD;
  &#xD;
            -  In the opinion of the investigator, inability to observe the contraindications of the&#xD;
               study drugs, or failure to comply to the study protocol or research team's&#xD;
               recommendations (e.g., changing pump parameters, ketone measurements).&#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>Melissa-Rosina Pasqua, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Research Institute of the McGill University Health Centre</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Adelyn Moore</last_name>
      <phone>(438) 866-4807</phone>
      <email>adelyn.moore@mail.mcgill.ca</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
      <investigator_full_name>Melissa-Rosina Pasqua</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>diabetes</keyword>
    <keyword>empagliflozin</keyword>
    <keyword>26-week</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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Empagliflozin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06021145
  org study id: 2024-9953
  nct id: NCT06021145
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this 26-week multicenter, randomized, parallel, placebo-controlled trial is to
        test the effectiveness of empagliflozin use in conjunction with automated insulin delivery
        (AID) to improve glucose control in individuals with type 1 diabetes who do not meet target
        recommendations for time in range (3.9-10.0 mmol/L). The main question it aims to answer is:
  
        - Will use of empagliflozin (2.5 mg/day) increase time spent in the target range of 3.9 to
        10.0 mmol/L compared to placebo for individuals on an AID system who do not meet glycemic
        targets?
  
        Participants will either take 2.5 mg of empagliflozin or a placebo daily for 26 weeks while
        remaining on their current AID system.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo)
  time frame: 4 weeks
  description: Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on an automated insulin delivery system vs empagliflozin (2.5 mg) on an automated insulin delivery system. Percent measured as per continuous glucose monitor (CGM) data.
  measure: Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L
  time frame: 4 weeks
  description: Percent as per CGM data
  measure: Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L
  time frame: 4 weeks
  description: Percent as per CGM data
  measure: Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L
  time frame: 4 weeks
  description: Percent as per CGM data
  measure: Mean glucose levels
  time frame: 4 weeks
  description: Defined as per CGM data, in mmol/L
  measure: Standard deviation of glucose levels
  time frame: 4 weeks
  description: Defined as per CGM data, in mmol/L
  measure: Coefficient of variance of glucose levels
  time frame: 4 weeks
  description: Percent as per CGM data
  measure: Total insulin delivery (overall, basal, and bolus)
  time frame: 4 weeks
  description: Defined as per participant's pump data
  measure: Mean daily carbohydrate intake
  time frame: 4 weeks
  description: Defined as per participant's pump data
  measure: HbA1c
  time frame: 26 weeks
  description: Percent as per blood test
  measure: Estimated glomerular filtration rate (eGFR)
  time frame: 26 weeks
  description: mL/min/1.73 m^2 as per blood test
  measure: Lipid profile
  time frame: 26 weeks
  description: Includes measurements in mmol/L as per blood test: total cholesterol, triglycerides, HDL-C, LDL-C, nonHDL-C
  measure: Brain Natriuretic Peptide (NT-pro-BNP)
  time frame: 26 weeks
  description: ng/L as per blood test
  measure: Liver profile - bilirubin
  time frame: 26 weeks
  description: umol/L as per blood test
  measure: Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP)
  time frame: 26 weeks
  description: U/L as per blood test
  measure: Measurement of body mass: weight and height
  time frame: 26 weeks
  description: Body measurement as described (weight in kilograms and height in meters). Weight and height will be combined to report body mass index in kg/m^2.
  measure: Waist and hip circumference, and waist-to-hip ratio
  time frame: 26 weeks
  description: Body measurements as described (waist and hip circumference in centimeters). Waist and hip cirumference will be combined to report waist-to-hip ratio.
  measure: Heart rate
  time frame: 26 weeks
  description: Body measurement as described (beats per minutes)
  measure: Blood pressure
  time frame: 26 weeks
  description: Body measurement as described (diastolic and systolic pressure; mmHg)
  measure: Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire
  time frame: 26 weeks
  description: Self-report scale (1 min = "not a problem" to 6 max = "a very serious problem") that assesses a participant's distress surrounding their diabetes with higher scores correlating to higher distress.
  measure: Average scores between interventions based on Hypoglycemic Fear Survey - II
  time frame: 26 weeks
  description: Likert scale (1 min to 5 max) that assesses a participant's worry surrounding hypoglycemia with higher scores indicating increased fear of hypoglycemia.
  measure: Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire
  time frame: 26 weeks
  description: Self-report scale (0 min = "very dissatisfied" to 6 max = "very satisfied") that assesses a participant's satisfaction surrounding the treatment for their diabetes with higher scores indicating greater satisfaction with treatment.
  measure: Fasting ketone levels
  time frame: 7 days
  description: As per ketone test strip and meter; measured by participant
  arm group label: Empagliflozin 2.5 mg daily
  arm group type: Experimental
  description: Empagliflozin is a sodium/glucose cotransporter 2 inhibitor (SGLT2i) that inhibits glucose reabsorption in the kidney. In this study, a capsule of empagliflozin 2.5 mg will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.
  arm group label: Placebo
  arm group type: Active Comparator
  description: As a control, a placebo capsule will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.
  intervention type: Drug
  intervention name: Empagliflozin
  description: 26-week use of automated insulin delivery system with empagliflozin (2.5 mg daily) in individuals with suboptimal time in range.
  arm group label: Empagliflozin 2.5 mg daily
  intervention type: Drug
  intervention name: Placebo
  description: 26-week use of automated insulin delivery system with placebo (daily) in individuals with suboptimal time in range.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Melissa-Rosina Pasqua, MD
  role: Principal Investigator
  affiliation: Research Institute of the McGill University Health Centre
  last name: Adelyn Moore
  phone: (438) 866-4807
  email: adelyn.moore@mail.mcgill.ca
  responsible party type: Principal Investigator
  investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
  investigator full name: Melissa-Rosina Pasqua
  investigator title: Principal Investigator
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 1
  mesh term: Empagliflozin
  sharing ipd: No