Back to resultsEffect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting (CLASS17)
Primary Purpose
Type1 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
empagliflozin
artificial pancreas
Sponsored by
About this trial
This is an interventional treatment trial for Type1 Diabetes Mellitus focused on measuring Type 1 Diabetes Mellitus, Empagliflozin, Artificial Pancreas, SGLT2 inhibitor, insulin pump, closed loop
Eligibility Criteria
Inclusion Criteria:
- Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.
- Males and females ≥ 18 years of age.
- 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.
- Insulin pump therapy use for at least 3 months.
- HbA1c ≤ 10%.
- eGFR ≥ 60 mL/min/1.73 m² as calculated by the CKD-EPI formula.
- 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:
- Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
- Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
- Renal insufficiency (characterized at eGFR below 60 mmol/l at the beginning of the trial)
- History of pheochromocytoma or insulinoma
- Beta-blockers at high dose (interference with glucose management).
- Chronic acetaminophen treatment (can interfere with glucose sensor measurements).
- Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding).
- Current use of other non-insulin adjunct anti-hyperglycemic drug or use within 30 days prior to screening.
- Use of loop diuretics (e.g. furosemide, due to possible interference with study drug mechanism of action).
- Ongoing or planned pregnancy or breastfeeding.
- Severe hypoglycemic episode within one month prior to Visit 1.
- Diabetic ketoacidosis in the last 3 months prior to Visit 1.
- Current use of glucocorticoid medication except low stable dose and inhaled steroids (can interfere with glucose sensor measurements).
- Known or suspected allergy to the trial products.
- Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
- Anticipating a significant change in exercise regimen between initiation of two intervention blocks (i.e. starting or stopping an organized sport).
- Recent history of genital or urinary infection (<1 month prior to Visit 1) or history of recurrent urinary tract infections.
- Difficulty in using the artificial pancreas system following training.
Sites / Locations
- Sinai Health System
- McGill University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Empagliflozin arm
Placebo arm
Arm 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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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
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.
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.
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
Absolute number of hypoglycemia events I.
Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on sensor glucose levels
Absolute number of hypoglycemia events II.
Number of symptomatic hypoglycemic events < 3.9 mmol/l or below 3.3 mmol/l without symptoms
Absolute number of hypoglycemia events III.
Number of treated hypoglycemic events
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)
Statistical characteristics of glucose profile II.
Standard deviation of glucose levels
Amount of total insulin delivery during interventions
Total insulin delivery measured by mean of units per day
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.
Mean fasting capillary ketone levels
Mean fasting capillary ketone levels.
Number of episodes of diabetic ketoacidosis
Number of episodes of diabetic ketoacidosis
Number of technical adverse events
Number of events when algorithm crashes or needs to be overridden for safety reasons.
Full Information
NCT ID
NCT03979352
First Posted
April 13, 2019
Last Updated
June 3, 2022
Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
1. Study Identification
Unique Protocol Identification Number
NCT03979352
Brief Title
Effect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting
Acronym
CLASS17
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
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
August 31, 2021 (Actual)
Study Completion Date
August 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1 Diabetes Mellitus
Keywords
Type 1 Diabetes Mellitus, Empagliflozin, Artificial Pancreas, SGLT2 inhibitor, insulin pump, closed loop
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Empagliflozin arm
Arm Type
Active Comparator
Arm 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 Title
Placebo arm
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
empagliflozin
Intervention Description
Treatment with empagliflozin 25mg orally once a day
Intervention Type
Device
Intervention Name(s)
artificial pancreas
Intervention Description
Insulin delivery via a closed loop single-hormone artificial pancreas system.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
20 weeks
Title
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
Description
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.
Time Frame
20 weeks
Title
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
Description
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.
Time Frame
20 weeks
Title
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
Description
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.
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
20 weeks
Title
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
Description
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.
Time Frame
20 weeks
Title
Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups
Description
Hypoglycemia: Percentage of time with glucose <3.9 mmol/L applied to each of the primary and secondary outcome comparator groups.
Time Frame
20 weeks
Title
Percentage of time spent in hypoglycemia, euglycemia and hyperglycemia
Description
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
Time Frame
20 weeks
Title
Absolute number of hypoglycemia events I.
Description
Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on sensor glucose levels
Time Frame
20 weeks
Title
Absolute number of hypoglycemia events II.
Description
Number of symptomatic hypoglycemic events < 3.9 mmol/l or below 3.3 mmol/l without symptoms
Time Frame
20 weeks
Title
Absolute number of hypoglycemia events III.
Description
Number of treated hypoglycemic events
Time Frame
20 weeks
Title
Statistical characteristics of glucose profile I.
Description
Area under the curve of hypoglycemic glucose values (below 3.9 mmol/L, 3.3 mmol/L and 2.8 mmol/L)
Time Frame
20 weeks
Title
Statistical characteristics of glucose profile II.
Description
Standard deviation of glucose levels
Time Frame
20 weeks
Title
Amount of total insulin delivery during interventions
Description
Total insulin delivery measured by mean of units per day
Time Frame
20 weeks
Title
Change in HbA1c
Description
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.
Time Frame
20 weeks
Title
Mean fasting capillary ketone levels
Description
Mean fasting capillary ketone levels.
Time Frame
20 weeks
Title
Number of episodes of diabetic ketoacidosis
Description
Number of episodes of diabetic ketoacidosis
Time Frame
20 weeks
Title
Number of technical adverse events
Description
Number of events when algorithm crashes or needs to be overridden for safety reasons.
Time Frame
20 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.
Males and females ≥ 18 years of age.
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.
Insulin pump therapy use for at least 3 months.
HbA1c ≤ 10%.
eGFR ≥ 60 mL/min/1.73 m² as calculated by the CKD-EPI formula.
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:
Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
Renal insufficiency (characterized at eGFR below 60 mmol/l at the beginning of the trial)
History of pheochromocytoma or insulinoma
Beta-blockers at high dose (interference with glucose management).
Chronic acetaminophen treatment (can interfere with glucose sensor measurements).
Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding).
Current use of other non-insulin adjunct anti-hyperglycemic drug or use within 30 days prior to screening.
Use of loop diuretics (e.g. furosemide, due to possible interference with study drug mechanism of action).
Ongoing or planned pregnancy or breastfeeding.
Severe hypoglycemic episode within one month prior to Visit 1.
Diabetic ketoacidosis in the last 3 months prior to Visit 1.
Current use of glucocorticoid medication except low stable dose and inhaled steroids (can interfere with glucose sensor measurements).
Known or suspected allergy to the trial products.
Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
Anticipating a significant change in exercise regimen between initiation of two intervention blocks (i.e. starting or stopping an organized sport).
Recent history of genital or urinary infection (<1 month prior to Visit 1) or history of recurrent urinary tract infections.
Difficulty in using the artificial pancreas system following training.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce Perkins, MD
Organizational Affiliation
Samuel Lunenfeld Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sinai Health System
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 3L9
Country
Canada
Facility Name
McGill University
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Effect of SGLT2i in Conjunction With the Artificial Pancreas on Improving the Glycemia in T1DM in the Outpatient Setting
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