Clinical trial NCT03979352: Effect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type1 Diabetes Mellitus
Keywords: Type 1 Diabetes Mellitus
Empagliflozin
Artificial Pancreas
SGLT2 inhibitor
insulin pump
closed loop
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
Collaborators: name: McGill University Health Centre/Research Institute of the McGill University Health Centre
First posted: 2019-06-07
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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
timeFrame: 20 weeks
measure: 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
timeFrame: 20 weeks
measure: 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
timeFrame: 20 weeks
measure: 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
timeFrame: 20 weeks
Secondary outcomes:
measure: 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
timeFrame: 20 weeks
measure: 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
timeFrame: 20 weeks
measure: Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups
timeFrame: 20 weeks
measure: Percentage of time spent in hypoglycemia, euglycemia and hyperglycemia
timeFrame: 20 weeks
measure: Absolute number of hypoglycemia events I.
timeFrame: 20 weeks
measure: Absolute number of hypoglycemia events II.
timeFrame: 20 weeks
measure: Absolute number of hypoglycemia events III.
timeFrame: 20 weeks
measure: Statistical characteristics of glucose profile I.
timeFrame: 20 weeks
measure: Statistical characteristics of glucose profile II.
timeFrame: 20 weeks
measure: Amount of total insulin delivery during interventions
timeFrame: 20 weeks
measure: Change in HbA1c
timeFrame: 20 weeks
measure: Mean fasting capillary ketone levels
timeFrame: 20 weeks
measure: Number of episodes of diabetic ketoacidosis
timeFrame: 20 weeks
measure: Number of technical adverse events
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sinai Health System
state: Ontario
city: Montréal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Samuel Lunenfeld Research Institute
name: Bruce Perkins, MD
role: PRINCIPAL_INVESTIGATOR
References: