Effect of SGLT2 Inhibition on Improving the Glycemic Performance of the Single Hormone Artificial Pancreas Configuration in Type 1 Diabetes in the Outpatient Setting - A Randomized Placebo Controlled Cross-Over Multicentre Clinical Trial

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

Sponsors

Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

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

Source Samuel Lunenfeld Research Institute, Mount Sinai Hospital
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.

Overall Status Recruiting
Start Date August 1, 2019
Completion Date August 31, 2021
Primary Completion Date August 31, 2021
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L compared between 4- weeks AP on empagliflozin and 4-weeks AP with placebo 20 weeks
Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L compared between 4- weeks conventional pump therapy on empagliflozin and 4- weeks conventional pump therapy with placebo 20 weeks
Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L on 4- weeks automated AP on empagliflozin when compared to 4-weeks conventional pump therapy on empagliflozin 20 weeks
Percentage of time spent in sensor glucose target range defined as between 3.9 and 7.8 mmol/L on 4- weeks automated AP on empagliflozin when compared to 4-weeks conventional pump therapy with placebo 20 weeks
Secondary Outcome
Measure Time Frame
Percentage of time spent in sensor glucose target range defined as between 3.9 and 10.0 mmol/L compared between 4- weeks conventional pump therapy on empagliflozin and 4-weeks AP on empagliflozin 20 weeks
Percentage of time spent in sensor glucose target range defined as between 3.9 and 10.0 mmol/L compared between 4- weeks AP on empagliflozin and 4- weeks AP with placebo 20 weeks
Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups 20 weeks
Percentage of time spent in hypoglycemia, euglycemia and hyperglycemia 20 weeks
Absolute number of hypoglycemia events I. 20 weeks
Absolute number of hypoglycemia events II. 20 weeks
Absolute number of hypoglycemia events III. 20 weeks
Statistical characteristics of glucose profile I. 20 weeks
Statistical characteristics of glucose profile II. 20 weeks
Amount of total insulin delivery during interventions 20 weeks
Change in HbA1c 20 weeks
Mean fasting capillary ketone levels 20 weeks
Number of episodes of diabetic ketoacidosis 20 weeks
Number of technical adverse events 20 weeks
Enrollment 28
Condition
Intervention

Intervention type: Drug

Intervention name: empagliflozin

Description: Treatment with empagliflozin 25mg orally once a day

Arm group label: Empagliflozin arm

Intervention type: Device

Intervention name: artificial pancreas

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

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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Bruce Perkins, MD Principal Investigator Samuel Lunenfeld Research Institute
Overall Contact

Last name: Andrej Orszag

Phone: 416-586-4800

Phone ext: 7625

Email: [email protected]

Location
facility status contact investigator
Sinai Health System | Toronto, Ontario, M5T 3L9, Canada Recruiting Andrej Orszag 416-586-4800 [email protected] Bruce A. Perkins, MD Principal Investigator
McGill University | Montréal, Quebec, H3A 2B4, Canada Not yet recruiting Jennifer René, RN 418- 558-0742 Ahmad Haidar Principal Investigator
Location Countries

Canada

Verification Date

November 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Empagliflozin arm

Arm group type: Active Comparator

Description: 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.

Arm group label: Placebo arm

Arm group type: Placebo Comparator

Description: 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.

Acronym CLASS17
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov