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Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes

Primary Purpose

Type 1 Diabetes

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Empagliflozin
Placebo
Sponsored by
McGill University Health Centre/Research Institute of the McGill University Health Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring diabetes, empagliflozin, 26-week

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Individuals ≥ 18 years of age. A clinical diagnosis of type 1 diabetes for at least one year, as per the investigators' clinical judgment (confirmatory C-peptide and antibodies will not be required). Minimum 3-month use of a commercial advanced AID system. Time in range (3.9 to 10.0 mmol/L) < 70% on their personal AID system in the 30 days prior to screening (with minimum 70% time spent in closed-loop mode). Agreement to use a highly effective method of birth control for individuals of child-bearing age and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche who have not reached menopause and who do not have a disclosed medical condition causing sterility (ex: hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause. Exclusion Criteria: Current or ≤ 2 week use of any anti-hyperglycemic agent other than insulin (such as SGTL2i). Current or ≤ 1 month use of Glucagon-like Peptide 1 (GLP1)-Receptor Agonists. Current or ≤ 1 month use of supraphysiological doses of oral or intravenous glucocorticoids. Planned or ongoing very low carbohydrate diet (< 50g/day). Glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as per CKD-EPI formula with creatinine levels measured within the last 12 months. Use of hydroxyurea. Planned or ongoing pregnancy. Breastfeeding. Ongoing active risk of recurrent genito-urinary infections, as per the clinical judgement of the investigators. Severe hypoglycemic episode within 1 month of screening, defined as an event resulting in seizure, loss of consciousness, or need to present to the emergency department. Diabetic ketoacidosis within 6 months of screening, defined as an event requiring the need to present to medical attention and administration of intravenous insulin. Any serious medical illness likely to interfere with the ability to complete the trial per the judgment of the investigators. Clinically significant retinopathy as judged by the investigator. Recent (< 3 months) acute macrovascular event (ex: acute coronary syndrome or cardiac surgery). Prior serious reaction to SGLT2i. Use of the Medtronic 670G or 770G system in the last 30 days. In the opinion of the investigator, inability to observe the contraindications of the study drugs, or failure to comply to the study protocol or research team's recommendations (e.g., changing pump parameters, ketone measurements).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Empagliflozin 2.5 mg daily

    Placebo

    Arm 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.

    As a control, a placebo capsule will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.

    Outcomes

    Primary Outcome Measures

    Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo)
    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.

    Secondary Outcome Measures

    Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L
    Percent as per CGM data
    Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L
    Percent as per CGM data
    Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L
    Percent as per CGM data
    Mean glucose levels
    Defined as per CGM data, in mmol/L
    Standard deviation of glucose levels
    Defined as per CGM data, in mmol/L
    Coefficient of variance of glucose levels
    Percent as per CGM data
    Total insulin delivery (overall, basal, and bolus)
    Defined as per participant's pump data
    Mean daily carbohydrate intake
    Defined as per participant's pump data
    HbA1c
    Percent as per blood test
    Estimated glomerular filtration rate (eGFR)
    mL/min/1.73 m^2 as per blood test
    Lipid profile
    Includes measurements in mmol/L as per blood test: total cholesterol, triglycerides, HDL-C, LDL-C, nonHDL-C
    Brain Natriuretic Peptide (NT-pro-BNP)
    ng/L as per blood test
    Liver profile - bilirubin
    umol/L as per blood test
    Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP)
    U/L as per blood test
    Measurement of body mass: weight and height
    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.
    Waist and hip circumference, and waist-to-hip ratio
    Body measurements as described (waist and hip circumference in centimeters). Waist and hip cirumference will be combined to report waist-to-hip ratio.
    Heart rate
    Body measurement as described (beats per minutes)
    Blood pressure
    Body measurement as described (diastolic and systolic pressure; mmHg)
    Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire
    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.
    Average scores between interventions based on Hypoglycemic Fear Survey - II
    Likert scale (1 min to 5 max) that assesses a participant's worry surrounding hypoglycemia with higher scores indicating increased fear of hypoglycemia.
    Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire
    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.
    Fasting ketone levels
    As per ketone test strip and meter; measured by participant

    Full Information

    First Posted
    August 21, 2023
    Last Updated
    August 31, 2023
    Sponsor
    McGill University Health Centre/Research Institute of the McGill University Health Centre
    Collaborators
    Diabetes Canada
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06021145
    Brief Title
    Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    October 2024 (Anticipated)
    Study Completion Date
    October 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    McGill University Health Centre/Research Institute of the McGill University Health Centre
    Collaborators
    Diabetes Canada

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 1 Diabetes
    Keywords
    diabetes, empagliflozin, 26-week

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    46 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Empagliflozin 2.5 mg daily
    Arm Type
    Experimental
    Arm 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 Title
    Placebo
    Arm Type
    Active Comparator
    Arm 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(s)
    Empagliflozin
    Intervention Description
    26-week use of automated insulin delivery system with empagliflozin (2.5 mg daily) in individuals with suboptimal time in range.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    26-week use of automated insulin delivery system with placebo (daily) in individuals with suboptimal time in range.
    Primary Outcome Measure Information:
    Title
    Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo)
    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.
    Time Frame
    4 weeks
    Secondary Outcome Measure Information:
    Title
    Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L
    Description
    Percent as per CGM data
    Time Frame
    4 weeks
    Title
    Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L
    Description
    Percent as per CGM data
    Time Frame
    4 weeks
    Title
    Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L
    Description
    Percent as per CGM data
    Time Frame
    4 weeks
    Title
    Mean glucose levels
    Description
    Defined as per CGM data, in mmol/L
    Time Frame
    4 weeks
    Title
    Standard deviation of glucose levels
    Description
    Defined as per CGM data, in mmol/L
    Time Frame
    4 weeks
    Title
    Coefficient of variance of glucose levels
    Description
    Percent as per CGM data
    Time Frame
    4 weeks
    Title
    Total insulin delivery (overall, basal, and bolus)
    Description
    Defined as per participant's pump data
    Time Frame
    4 weeks
    Title
    Mean daily carbohydrate intake
    Description
    Defined as per participant's pump data
    Time Frame
    4 weeks
    Title
    HbA1c
    Description
    Percent as per blood test
    Time Frame
    26 weeks
    Title
    Estimated glomerular filtration rate (eGFR)
    Description
    mL/min/1.73 m^2 as per blood test
    Time Frame
    26 weeks
    Title
    Lipid profile
    Description
    Includes measurements in mmol/L as per blood test: total cholesterol, triglycerides, HDL-C, LDL-C, nonHDL-C
    Time Frame
    26 weeks
    Title
    Brain Natriuretic Peptide (NT-pro-BNP)
    Description
    ng/L as per blood test
    Time Frame
    26 weeks
    Title
    Liver profile - bilirubin
    Description
    umol/L as per blood test
    Time Frame
    26 weeks
    Title
    Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP)
    Description
    U/L as per blood test
    Time Frame
    26 weeks
    Title
    Measurement of body mass: weight and height
    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.
    Time Frame
    26 weeks
    Title
    Waist and hip circumference, and waist-to-hip ratio
    Description
    Body measurements as described (waist and hip circumference in centimeters). Waist and hip cirumference will be combined to report waist-to-hip ratio.
    Time Frame
    26 weeks
    Title
    Heart rate
    Description
    Body measurement as described (beats per minutes)
    Time Frame
    26 weeks
    Title
    Blood pressure
    Description
    Body measurement as described (diastolic and systolic pressure; mmHg)
    Time Frame
    26 weeks
    Title
    Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire
    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.
    Time Frame
    26 weeks
    Title
    Average scores between interventions based on Hypoglycemic Fear Survey - II
    Description
    Likert scale (1 min to 5 max) that assesses a participant's worry surrounding hypoglycemia with higher scores indicating increased fear of hypoglycemia.
    Time Frame
    26 weeks
    Title
    Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire
    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.
    Time Frame
    26 weeks
    Title
    Fasting ketone levels
    Description
    As per ketone test strip and meter; measured by participant
    Time Frame
    7 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Individuals ≥ 18 years of age. A clinical diagnosis of type 1 diabetes for at least one year, as per the investigators' clinical judgment (confirmatory C-peptide and antibodies will not be required). Minimum 3-month use of a commercial advanced AID system. Time in range (3.9 to 10.0 mmol/L) < 70% on their personal AID system in the 30 days prior to screening (with minimum 70% time spent in closed-loop mode). Agreement to use a highly effective method of birth control for individuals of child-bearing age and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche who have not reached menopause and who do not have a disclosed medical condition causing sterility (ex: hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause. Exclusion Criteria: Current or ≤ 2 week use of any anti-hyperglycemic agent other than insulin (such as SGTL2i). Current or ≤ 1 month use of Glucagon-like Peptide 1 (GLP1)-Receptor Agonists. Current or ≤ 1 month use of supraphysiological doses of oral or intravenous glucocorticoids. Planned or ongoing very low carbohydrate diet (< 50g/day). Glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as per CKD-EPI formula with creatinine levels measured within the last 12 months. Use of hydroxyurea. Planned or ongoing pregnancy. Breastfeeding. Ongoing active risk of recurrent genito-urinary infections, as per the clinical judgement of the investigators. Severe hypoglycemic episode within 1 month of screening, defined as an event resulting in seizure, loss of consciousness, or need to present to the emergency department. Diabetic ketoacidosis within 6 months of screening, defined as an event requiring the need to present to medical attention and administration of intravenous insulin. Any serious medical illness likely to interfere with the ability to complete the trial per the judgment of the investigators. Clinically significant retinopathy as judged by the investigator. Recent (< 3 months) acute macrovascular event (ex: acute coronary syndrome or cardiac surgery). Prior serious reaction to SGLT2i. Use of the Medtronic 670G or 770G system in the last 30 days. In the opinion of the investigator, inability to observe the contraindications of the study drugs, or failure to comply to the study protocol or research team's recommendations (e.g., changing pump parameters, ketone measurements).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Adelyn Moore
    Phone
    (438) 866-4807
    Email
    adelyn.moore@mail.mcgill.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Melissa-Rosina Pasqua, MD
    Organizational Affiliation
    Research Institute of the McGill University Health Centre
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes

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