Low Dose Empagliflozin in Adults With Type 1 Diabetes on Closed Loop Insulin System

• Status: Recruiting
• Trial end date: 2021-08-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: McGill University

Criteria

Inclusion Criteria:

• A clinical diagnosis of type 1 diabetes for at least one year, as per their treating diabetes physician in agreement with the primary investigator's clinical judgment (confirmatory C-peptide and antibodies will not be required)

• HbA1c between 7 and 10.5% (both extremes inclusive), performed within the last 6 months prior to study inclusion

• Insulin pump use (of any modality) for minimum 3 months

• Agreement to the use of highly effective method of birth control in women of child-bearing age and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche and have not reached menopause or have a disclosed medical condition causing sterility (e.g. hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause.

• Time in range (3.9 - 10.0 mmol/L) < 70% as per CGM readings of the last 10 days during a 2-week run-in period on the closed-loop insulin delivery system.

Exclusion Criteria:

• Current or < 2 week use of any other anti-hyperglycemic agent other than insulin

• Current or
• Requirement for regular use of acetaminophen (which may decrease CGM fidelity)

• Planned or ongoing pregnancy

• Breastfeeding individuals

• Severe hypoglycemic episode within the last 3 months, defined as an event where glucose was < 4 mmol/L resulting in seizure, loss of consciousness, or need to present to the emergency department

• Severe diabetic ketoacidosis within the last 3 years ("severe" referring to need to present to medical attention and requirement of intravenous insulin)

• Active infection of any kind at the time of study enrolment, or any active foot ulcer

• Recurrent infections (i.e. more than 2 in 1 year) of the following: genital, urinary tract infections, soft tissue, joint, or bone

• Known severe peripheral vascular disease including the following: symptomatic claudication, loss of peripheral pulses, signs of peripheral arterial insufficiency as per initial clinical exam, previously documented insufficiency as per ankle or toe brachial index, prior amputations due to peripheral vascular disease

• Osteoporosis defined as prior fragility fracture, previously measured bone mineral density with T or Z score < -2.5, or need for anti-osteoporotic medications

• Glomerular filtration rate less than 30 mL/minutes/1.73 m2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.

• Any serious medical or psychiatric illness likely to interfere with study participation as per the judgment of the investigator (e.g. cirrhosis, active cancer, decompensated schizophrenia)

• Prior adverse reaction to SGLT2 inhibitors (e.g. empagliflozin, dapagliflozin)

• Inability to travel to the research center within 3 hours if needed during the study interventions

• Failure to comply to the study protocol and/or research group's recommendations (e.g. change in pump parameters, ketone measurement)

• Inability or unwillingness to comply to safe diabetes management in the view of the study group (e.g. inappropriate treatment of hypoglycemia or lack thereof)

• Anticipation of a significant change in exercise regimen between initiation of the intervention blocks (i.e. starting or stopping an organized sport)

• Any demonstrate of difficulty in using the McGill Artificial Pancreas system following training, as per investigator's judgment

• Concern for safety of the participant, as per the clinical judgment of the primary investigator