Effect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting

NCT ID: NCT03979352

Last Updated: 2022-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2021-08-31

Brief Summary

The most advanced configurations of the Artificial Pancreas (AP) have not yet been demonstrated to sufficiently maximize time in target glycemia. One limitation is the challenge of postprandial glycemic control, which currently requires ongoing patient engagement for accurate and detailed bolus dose estimation for meals. Sodium Glucose Linked Transporter 2 Inhibition (SGLT2i) provides an additional mechanism to attenuate post-prandial glycemic excursion, and may represent a strategy that could further alleviate carbohydrate counting burden and improve the performance of AP configurations. This trial aims to compare - using a randomized, masked placebo-controlled, crossover, multicenter design - the efficacy of the SGLT2i empagliflozin 25 mg oral per day each in the setting of single-hormone automated AP and conventional insulin pump therapy on the proportion of time spent in target and in hypoglycemia each during a 4-week day-and-night period. The pilot trial aims to enroll 28 adult patients with type 1 diabetes (T1D) across 2 research sites (one in Toronto and one in Montreal) and includes a 2- week therapy optimization run-in period, 4-weeks for each of the two AP intervention arms, and a 1- week washout in between the pharmacological intervention sequences. Glucose levels will be measured by continuous glucose monitoring (G5, Dexcom Inc.). Insulin will be infused using a subcutaneous infusion pump (t-slim, Tandem Diabetes Care) and communication between pumps and the algorithm will be implemented using Android Smartphone devices and Bluetooth technology communication.

Conditions

Type1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Empagliflozin arm

Participant will be treated by empagliflozin for 8 weeks. During these 8 weeks he will use artificial pancreas to deliver the insulin for 4 weeks and conventional pump therapy for remaining 4 weeks, in a random order.

After finishing the entire arm intervention participant will undergo 7 day of washout and enters the placebo arm.

Participant and research staff is blinded to arm assignment.

Group Type: ACTIVE_COMPARATOR

empagliflozin

Intervention Type: DRUG

Treatment with empagliflozin 25mg orally once a day

artificial pancreas

Intervention Type: DEVICE

Insulin delivery via a closed loop single-hormone artificial pancreas system.

Placebo arm

Participant will take placebo for 8 weeks. During these 8 weeks he will use artificial pancreas to deliver the insulin for 4 weeks and conventional pump therapy for remaining 4 weeks, in a random order.

After finishing the entire arm intervention participant will undergo 7 day of washout and enters the empagliflozin arm.

Participant and research staff is blinded to arm assignment.

Group Type: PLACEBO_COMPARATOR

artificial pancreas

Intervention Type: DEVICE

Insulin delivery via a closed loop single-hormone artificial pancreas system.

Interventions

empagliflozin

Treatment with empagliflozin 25mg orally once a day

Intervention Type: DRUG

artificial pancreas

Insulin delivery via a closed loop single-hormone artificial pancreas system.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.

2. Males and females ≥ 18 years of age.

3. Clinical diagnosis of T1D for at least one year. The diagnosis of T1D is based on the investigator's clinical judgment; C peptide level and antibody determinations are not planned.

4. Insulin pump therapy use for at least 3 months.

5. HbA1c ≤ 10%.

6. eGFR ≥ 60 mL/min/1.73 m² as calculated by the CKD-EPI formula.

7. Women of child-bearing potential must be ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly.

Exclusion Criteria

1. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.

2. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.

3. Renal insufficiency (characterized at eGFR below 60 mmol/l at the beginning of the trial)

4. History of pheochromocytoma or insulinoma

5. Beta-blockers at high dose (interference with glucose management).

6. Chronic acetaminophen treatment (can interfere with glucose sensor measurements).

7. Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding).

8. Current use of other non-insulin adjunct anti-hyperglycemic drug or use within 30 days prior to screening.

9. Use of loop diuretics (e.g. furosemide, due to possible interference with study drug mechanism of action).

10. Ongoing or planned pregnancy or breastfeeding.

11. Severe hypoglycemic episode within one month prior to Visit 1.

12. Diabetic ketoacidosis in the last 3 months prior to Visit 1.

13. Current use of glucocorticoid medication except low stable dose and inhaled steroids (can interfere with glucose sensor measurements).

14. Known or suspected allergy to the trial products.

15. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

16. Anticipating a significant change in exercise regimen between initiation of two intervention blocks (i.e. starting or stopping an organized sport).

17. Recent history of genital or urinary infection (<1 month prior to Visit 1) or history of recurrent urinary tract infections.

18. Difficulty in using the artificial pancreas system following training.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: collaborator

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce Perkins, MD

Role: PRINCIPAL_INVESTIGATOR

Samuel Lunenfeld Research Institute

Locations

Sinai Health System

Toronto, Ontario, Canada

McGill University

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

CLASS 17

Identifier Type: -

Identifier Source: org_study_id