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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03979352
Other study ID # CLASS 17
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date August 1, 2019
Est. completion date August 31, 2021

Study information

Verified date November 2019
Source Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 28
Est. completion date August 31, 2021
Est. primary completion date August 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Drug:
empagliflozin
Treatment with empagliflozin 25mg orally once a day
Device:
artificial pancreas
Insulin delivery via a closed loop single-hormone artificial pancreas system.

Locations

Country Name City State
Canada McGill University Montréal Quebec
Canada Sinai Health System Toronto Ontario

Sponsors (2)

Lead Sponsor Collaborator
Samuel Lunenfeld Research Institute, Mount Sinai Hospital McGill University Health Centre/Research Institute of the McGill University Health Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
Primary 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 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
Primary 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 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
Primary 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 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 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 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
Secondary 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 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
Secondary Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups. 20 weeks
Secondary Percentage of time spent in hypoglycemia, euglycemia and hyperglycemia Percentage of time spent in the different glucose sensor levels characterized by amount spent between 3.9 and 10.0 mmol/L, 3.9 and 7.8 mmol/L, above 10.0 mmol/L, above 13.9 mmol/L, above 16.7 mmol/l, below 3.9 mmol/L, below 3.3 mmol/L, below 2.8 mmol/L 20 weeks
Secondary Absolute number of hypoglycemia events I. Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on sensor glucose levels 20 weeks
Secondary Absolute number of hypoglycemia events II. Number of symptomatic hypoglycemic events < 3.9 mmol/l or below 3.3 mmol/l without symptoms 20 weeks
Secondary Absolute number of hypoglycemia events III. Number of treated hypoglycemic events 20 weeks
Secondary Statistical characteristics of glucose profile I. Area under the curve of hypoglycemic glucose values (below 3.9 mmol/L, 3.3 mmol/L and 2.8 mmol/L) 20 weeks
Secondary Statistical characteristics of glucose profile II. Standard deviation of glucose levels 20 weeks
Secondary Amount of total insulin delivery during interventions Total insulin delivery measured by mean of units per day 20 weeks
Secondary Change in HbA1c Change in HbA1c from baseline to after the first intervention and from the end of the first intervention to the end of the treatment period. 20 weeks
Secondary Mean fasting capillary ketone levels Mean fasting capillary ketone levels. 20 weeks
Secondary Number of episodes of diabetic ketoacidosis Number of episodes of diabetic ketoacidosis 20 weeks
Secondary Number of technical adverse events Number of events when algorithm crashes or needs to be overridden for safety reasons. 20 weeks
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