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

• ClinicalTrials.gov Identifier: NCT06021145
• Recruitment Status: Recruiting
• First Posted: September 1, 2023
• Last Update Posted: March 20, 2024
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborator: Diabetes Canada
• Information provided by (Responsible Party): Melissa-Rosina Pasqua, McGill University Health Centre/Research Institute of the McGill University Health Centre

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: Empagliflozin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: March 2024
• Estimated Primary Completion Date: October 2024
• Estimated Study Completion Date: October 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Empagliflozin 2.5 mg daily; 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.	Drug: Empagliflozin; 26-week use of automated insulin delivery system with empagliflozin (2.5 mg daily) in individuals with suboptimal time in range.
Active Comparator: Placebo; As a control, a placebo capsule will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.	Drug: Placebo; 26-week use of automated insulin delivery system with placebo (daily) in individuals with suboptimal time in range.

Outcome Measures

Primary Outcome Measures :

1. Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo) [ Time Frame: 4 weeks ]
   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 :

1. Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L [ Time Frame: 4 weeks ]
   Percent as per CGM data
2. Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L [ Time Frame: 4 weeks ]
   Percent as per CGM data
3. Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L [ Time Frame: 4 weeks ]
   Percent as per CGM data
4. Mean glucose levels [ Time Frame: 4 weeks ]
   Defined as per CGM data, in mmol/L
5. Standard deviation of glucose levels [ Time Frame: 4 weeks ]
   Defined as per CGM data, in mmol/L
6. Coefficient of variance of glucose levels [ Time Frame: 4 weeks ]
   Percent as per CGM data
7. Total insulin delivery (overall, basal, and bolus) [ Time Frame: 4 weeks ]
   Defined as per participant's pump data
8. Mean daily carbohydrate intake [ Time Frame: 4 weeks ]
   Defined as per participant's pump data
9. HbA1c [ Time Frame: 26 weeks ]
   Percent as per blood test
10. Estimated glomerular filtration rate (eGFR) [ Time Frame: 26 weeks ]
    mL/min/1.73 m^2 as per blood test
11. Lipid profile [ Time Frame: 26 weeks ]
    Includes measurements in mmol/L as per blood test: total cholesterol, triglycerides, HDL-C, LDL-C, nonHDL-C
12. Brain Natriuretic Peptide (NT-pro-BNP) [ Time Frame: 26 weeks ]
    ng/L as per blood test
13. Liver profile - bilirubin [ Time Frame: 26 weeks ]
    umol/L as per blood test
14. Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP) [ Time Frame: 26 weeks ]
    U/L as per blood test
15. Measurement of body mass: weight and height [ Time Frame: 26 weeks ]
    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.
16. Waist and hip circumference, and waist-to-hip ratio [ Time Frame: 26 weeks ]
    Body measurements as described (waist and hip circumference in centimeters). Waist and hip cirumference will be combined to report waist-to-hip ratio.
17. Heart rate [ Time Frame: 26 weeks ]
    Body measurement as described (beats per minutes)
18. Blood pressure [ Time Frame: 26 weeks ]
    Body measurement as described (diastolic and systolic pressure; mmHg)
19. Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire [ Time Frame: 26 weeks ]
    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.
20. Average scores between interventions based on Hypoglycemic Fear Survey - II [ Time Frame: 26 weeks ]
    Likert scale (1 min to 5 max) that assesses a participant's worry surrounding hypoglycemia with higher scores indicating increased fear of hypoglycemia.
21. Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire [ Time Frame: 26 weeks ]
    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.
22. Fasting ketone levels [ Time Frame: 7 days ]
    As per ketone test strip and meter; measured by participant

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Contacts

Contact: Adelyn Moore; (438) 866-4807; adelyn.moore@mail.mcgill.ca

Locations

Canada, Quebec

McGill University Health Centre; Recruiting

Montréal, Quebec, Canada, H4A 3J1

Contact: Adelyn Moore 4388664807 adelyn.moore@mail.mcgill.ca

Sponsors and Collaborators

McGill University Health Centre/Research Institute of the McGill University Health Centre

Diabetes Canada

Investigators

• Principal Investigator: Melissa-Rosina Pasqua, MD; Research Institute of the McGill University Health Centre

More Information

• Responsible Party: Melissa-Rosina Pasqua, Principal Investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
• ClinicalTrials.gov Identifier: NCT06021145
• Other Study ID Numbers: 2024-9953
• First Posted: September 1, 2023
• Last Update Posted: March 20, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The raw data (that is, insulin delivery, glucose levels and individual participant data) and informed consent form will be shared by the corresponding author, for academic purposes, subject to a material transfer agreement and approval of the McGill University Health Center's Research Ethics Board. All data shared will be de-identified. Raw data will be shared for non-commercial use upon reasonable request and a material transfer agreement.
• Supporting Materials: Informed Consent Form (ICF)

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

Keywords provided by Melissa-Rosina Pasqua, McGill University Health Centre/Research Institute of the McGill University Health Centre:

diabetes; empagliflozin; 26-week

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Empagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs