Back to resultsAlleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin (CLASS15)
Primary Purpose
Type1diabetes
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Empagliflozin 25mg
Single hormone artificial pancreas
Meal strategies
Sponsored by
About this trial
This is an interventional treatment trial for Type1diabetes focused on measuring T1DM, artificial pancreas, insulin pump, empagliflozin, SGLT2 inhibitor, carbohydrate counting
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of type 1 diabetes for at least one year.
- Use of insulin pump therapy for at least 3 months.
- HbA1c ≤ 10%.
- Women of childbearing potential must agree to use adequate birth control during participation in the study
Exclusion Criteria:
- Clinically significant nephropathy, neuropathy or retinopathy.
- Recent acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
- History of pheochromocytoma or insulinoma
- Use of loop diuretics, anticholinergic drugs, beta-blockers at high dose, glucocorticoids (except low stable dose and inhaled steroids), chronic acetaminophen treatment, chronic warfarin treatment
- Use of non-insulin adjunct anti-hyperglycaemic drug (e.g. metformin, glucagon-like peptide analogues, etc.).
- Ongoing or planned pregnancy or breastfeeding.
- Recent severe hypoglycemic episode prior to enrollment
- Recent diabetic ketoacidosis prior to enrollment
- Recent history of genital or urinary infection prior to enrollment
- History of lower limb amputation and recent history of leg or foot infection or wound
- Anticipating a significant change in exercise regimen between initiations of two intervention blocks (i.e. starting or stopping an organized sport).
Sites / Locations
- Sinai Health System
- Institut de recherches cliniques de Montréal
- McGill University Health Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Main arm
Arm Description
Single arm open-label cross-over study with random order of SGLT-2 inhibitor intervention (Empagliflozin 25mg po qd), in which each cross-over phase includes different meal strategies (carbohydrate counting, meal announcement, no meal announcement) on separate days in the setting of single hormone artificial pancreas
Outcomes
Primary Outcome Measures
Comparison of mean glucose levels between artificial pancreas (AP) with empagliflozin with no-meal announcement meal approach strategy and AP without empagliflozin with carb-counting meal approach strategy.
Non-inferiority comparison of mean 14-hour glucose level obtained by continuous glucose monitoring between i) the AP with empagliflozin with no meal-announcement and ii) the AP with quantitative carbohydrate-counting without empagliflozin.
Comparison of mean glucose levels between AP with empagliflozin with simple meal announcement strategy and AP without empagliflozin with carb-counting.
If there is a significant difference in the previous non-inferiority comparison, the following conditional primary comparison will be conducted:
Non-inferiority comparison of mean 14-hour sensor glucose level obtained by continuous glucose monitoring between i) the AP with empagliflozin with simple meal-announcement and ii) the AP with quantitative carbohydrate-counting without empagliflozin.
Secondary Outcome Measures
Time spent in hypoglycemia
Percentage of time spent in the following glucose sensor levels:
Between 3.9 and 10.0 mmol/l
Between 3.9 and 7.8 mmol/l
Above 7.8 mmol/l
Above 10.0 mmol/l
Above 13.9 mmol/l
Below 3.9 mmol/l
Below 3.3 mmol/l
Below 2.8 mmol/l.
Number of hypoglycemic events below 3.3 mmol/L
Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on continuous glucose monitoring sensor glucose level values.
Number of clinically remarkable hypoglycemic events
Number of symptomatic hypoglycemic events below 4.0 mmol/l or below 3.5 mmol/l without symptoms.
Number of treated hypoglycemic events
Number of hypoglycemic events or events perceived as hypoglycemia which prompt treatment by glucose or glucagon or overriding AP insulin dosing algorithm suggestion or by administering the regular meal earlier than planned.
Mean continuous glucose monitoring (CGM) glucose level
Comparison of mean CGM glucose levels between different meal interventions on and off empagliflozin.
Standard deviation of glucose levels
Comparison of values obtained from CGM on different meal intervention days.
Coefficient of variation of glucose levels
Comparison of values obtained from CGM on different meal intervention days.
Total insulin delivery
Comparison of total insulin delivered by AP on different meal intervention days.
Morning capillary ketone concentration
Safety outcome to assess risk of Empagliflozin related most serious side effect-diabetic ketoacidosis. Evaluated will be all days of study participation (i.e.not only meal intervention days)
Full Information
NCT ID
NCT03510000
First Posted
January 24, 2018
Last Updated
June 23, 2021
Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators
Canadian Diabetes Association, Institut de Recherches Cliniques de Montreal, McGill University Health Centre/Research Institute of the McGill University Health Centre
1. Study Identification
Unique Protocol Identification Number
NCT03510000
Brief Title
Alleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin
Acronym
CLASS15
Official Title
Alleviating Carbohydrate-Counting Burden in Type 1 Diabetes Using Artificial Pancreas and Sodium Glucose-Linked Transporter 2 Inhibition: A Randomized Open-Label Crossover Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
May 15, 2018 (Actual)
Primary Completion Date
November 21, 2019 (Actual)
Study Completion Date
November 21, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators
Canadian Diabetes Association, Institut de Recherches Cliniques de Montreal, 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
No
5. Study Description
Brief Summary
One of the challenges in the design of the artificial pancreas (AP) is preventing postprandial hyperglycemia. Beyond algorithmic solutions, one countermeasure to postprandial hyperglycemia that may enhance performance of the AP is the use of adjunctive-to-insulin medications such as those in the Sodium Glucose-Linked Transporter 2 inhibitor class. This study evaluates whether use of oral empagliflozin on the background of single-hormone AP can improve postprandial blood glucose control. The investigators will test this hypothesis in a cross-over trial design by comparing open-label empagliflozin versus placebo in the setting of AP on separate study days that involve carbohydrate counting, simple meal announcement and no meal announcement strategies.
Detailed Description
Empagliflozin is a novel anti-diabetic medication and has been approved in Canada. The labelled indication for use of empagliflozin in clinical practice is as an adjunct therapy to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. The investigators are proposing to use the medication as an adjunct anti-diabetic therapy in individuals with type 1 diabetes and would like to examine whether empagliflozin can alleviate need for carb-counting by eliminating post-prandial hyperglycemia in a setting of an artificial pancreas (AP).
The study is designed as a randomized open-label, crossover non-inferiority trial comparing empagliflozin 25 mg oral daily in the setting of the single-hormone AP to single-hormone AP without empagliflozin in adults with type 1 diabetes. The duration of the study for each of the participants is about 3-9 weeks and during this time three different meal announcement strategies for AP will be used, on and off empagliflozin treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1diabetes
Keywords
T1DM, artificial pancreas, insulin pump, empagliflozin, SGLT2 inhibitor, carbohydrate counting
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Main arm
Arm Type
Experimental
Arm Description
Single arm open-label cross-over study with random order of SGLT-2 inhibitor intervention (Empagliflozin 25mg po qd), in which each cross-over phase includes different meal strategies (carbohydrate counting, meal announcement, no meal announcement) on separate days in the setting of single hormone artificial pancreas
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 25mg
Intervention Description
Individuals will test insulin dosing during different meal strategies (carbohydrate counting, plain meal announcement, no meal announcement) in a setting of the single hormone artificial pancreas with or without SGLT2 inhibitor (empagliflozin) addition. After starting the empagliflozin therapy, there will be 1-2 weeks long therapy optimization period and afterwards meal strategies will be administered. Randomization will be used to determine whether participant will start meal strategies on empagliflozin or without empagliflozin, cross-over design enables all participants to undergo all combination of approaches.
Intervention Type
Device
Intervention Name(s)
Single hormone artificial pancreas
Intervention Description
Single hormone artificial pancreas will be used as a baseline background intervention standardizing the delivery and dosing of insulin. Artificial pancreas (insulin pump, continuous glucose monitoring device and dosing-suggestion algorithm) will be used by all participants on days when meal strategy intervention will be performed.
Intervention Type
Behavioral
Intervention Name(s)
Meal strategies
Intervention Description
Participants will use different approaches (strategies) to insulin dose estimation for ingested carbohydrates on study days. Goal of these various strategies is to recognize magnitude of empagliflozin effect in situations when artificial pancreas algorithm is working with information of different accuracy. Individual meal approach strategies include carbohydrate counting, meal size announcement and no meal announcement. The exception will be combination of no empagliflozin and no meal announcement, which didn't result in sufficient glucose control in previous trials therefore will not be repeated in a current trial. Meal approach strategies will occur on separate days- 5 days in total each day using one meal strategy for all meals during the day.
Primary Outcome Measure Information:
Title
Comparison of mean glucose levels between artificial pancreas (AP) with empagliflozin with no-meal announcement meal approach strategy and AP without empagliflozin with carb-counting meal approach strategy.
Description
Non-inferiority comparison of mean 14-hour glucose level obtained by continuous glucose monitoring between i) the AP with empagliflozin with no meal-announcement and ii) the AP with quantitative carbohydrate-counting without empagliflozin.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Comparison of mean glucose levels between AP with empagliflozin with simple meal announcement strategy and AP without empagliflozin with carb-counting.
Description
If there is a significant difference in the previous non-inferiority comparison, the following conditional primary comparison will be conducted:
Non-inferiority comparison of mean 14-hour sensor glucose level obtained by continuous glucose monitoring between i) the AP with empagliflozin with simple meal-announcement and ii) the AP with quantitative carbohydrate-counting without empagliflozin.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Secondary Outcome Measure Information:
Title
Time spent in hypoglycemia
Description
Percentage of time spent in the following glucose sensor levels:
Between 3.9 and 10.0 mmol/l
Between 3.9 and 7.8 mmol/l
Above 7.8 mmol/l
Above 10.0 mmol/l
Above 13.9 mmol/l
Below 3.9 mmol/l
Below 3.3 mmol/l
Below 2.8 mmol/l.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Number of hypoglycemic events below 3.3 mmol/L
Description
Number of hypoglycemic events (> 20 minutes) below 3.3 mmol/L based on continuous glucose monitoring sensor glucose level values.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Number of clinically remarkable hypoglycemic events
Description
Number of symptomatic hypoglycemic events below 4.0 mmol/l or below 3.5 mmol/l without symptoms.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Number of treated hypoglycemic events
Description
Number of hypoglycemic events or events perceived as hypoglycemia which prompt treatment by glucose or glucagon or overriding AP insulin dosing algorithm suggestion or by administering the regular meal earlier than planned.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Mean continuous glucose monitoring (CGM) glucose level
Description
Comparison of mean CGM glucose levels between different meal interventions on and off empagliflozin.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Standard deviation of glucose levels
Description
Comparison of values obtained from CGM on different meal intervention days.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Coefficient of variation of glucose levels
Description
Comparison of values obtained from CGM on different meal intervention days.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Total insulin delivery
Description
Comparison of total insulin delivered by AP on different meal intervention days.
Time Frame
After completing 5 meal interventions (3-9 weeks)
Title
Morning capillary ketone concentration
Description
Safety outcome to assess risk of Empagliflozin related most serious side effect-diabetic ketoacidosis. Evaluated will be all days of study participation (i.e.not only meal intervention days)
Time Frame
After completing 5 meal interventions (3-9 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of type 1 diabetes for at least one year.
Use of insulin pump therapy for at least 3 months.
HbA1c ≤ 10%.
Women of childbearing potential must agree to use adequate birth control during participation in the study
Exclusion Criteria:
Clinically significant nephropathy, neuropathy or retinopathy.
Recent acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
History of pheochromocytoma or insulinoma
Use of loop diuretics, anticholinergic drugs, beta-blockers at high dose, glucocorticoids (except low stable dose and inhaled steroids), chronic acetaminophen treatment, chronic warfarin treatment
Use of non-insulin adjunct anti-hyperglycaemic drug (e.g. metformin, glucagon-like peptide analogues, etc.).
Ongoing or planned pregnancy or breastfeeding.
Recent severe hypoglycemic episode prior to enrollment
Recent diabetic ketoacidosis prior to enrollment
Recent history of genital or urinary infection prior to enrollment
History of lower limb amputation and recent history of leg or foot infection or wound
Anticipating a significant change in exercise regimen between initiations of two intervention blocks (i.e. starting or stopping an organized sport).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce A. Perkins, MD
Organizational Affiliation
Samuel Lunenfeld Research Institute, TGRI
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
Institut de recherches cliniques de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada
Facility Name
McGill University Health Center
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Alleviating Carbohydrate-Counting Burden in T1DM Using Artificial Pancreas and Empagliflozin
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