Clinical trial NCT06021145: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Type 1 Diabetes
Keywords: diabetes
empagliflozin
26-week
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Diabetes Canada
First posted: 2023-09-01
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo)
timeFrame: 4 weeks
Secondary outcomes:
measure: Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L
timeFrame: 4 weeks
measure: Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L
timeFrame: 4 weeks
measure: Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L
timeFrame: 4 weeks
measure: Mean glucose levels
timeFrame: 4 weeks
measure: Standard deviation of glucose levels
timeFrame: 4 weeks
measure: Coefficient of variance of glucose levels
timeFrame: 4 weeks
measure: Total insulin delivery (overall, basal, and bolus)
timeFrame: 4 weeks
measure: Mean daily carbohydrate intake
timeFrame: 4 weeks
measure: HbA1c
timeFrame: 26 weeks
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: 26 weeks
measure: Lipid profile
timeFrame: 26 weeks
measure: Brain Natriuretic Peptide (NT-pro-BNP)
timeFrame: 26 weeks
measure: Liver profile - bilirubin
timeFrame: 26 weeks
measure: Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP)
timeFrame: 26 weeks
measure: Measurement of body mass: weight and height
timeFrame: 26 weeks
measure: Waist and hip circumference, and waist-to-hip ratio
timeFrame: 26 weeks
measure: Heart rate
timeFrame: 26 weeks
measure: Blood pressure
timeFrame: 26 weeks
measure: Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire
timeFrame: 26 weeks
measure: Average scores between interventions based on Hypoglycemic Fear Survey - II
timeFrame: 26 weeks
measure: Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire
timeFrame: 26 weeks
measure: Fasting ketone levels
timeFrame: 7 days
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: Research Institute of the McGill University Health Centre
name: Melissa-Rosina Pasqua, MD
role: PRINCIPAL_INVESTIGATOR
References: