Back to resultsAssessment of the Efficacy of the Artificial Pancreas Combined With a Qualitative Meal Size Estimation to Control Postprandial Glucose Levels
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Single-hormone closed-loop system
Insulin pump
Continuous glucose monitoring system
Aspart or Lispro
Carbohydrate counting
Simplified qualitative meal-size estimation strategy
3-week intervention
1-hour postprandial exercise (sub-study)
2-hour postprandial exercise (sub-study)
Exercise announcement and meal bolus reduction (sub-study)
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 diabetes, Artificial pancreas, Closed-loop system, Insulin, Postprandial glucose, Exercise
Eligibility Criteria
Inclusion criteria
- Males and females ≥ 18 years of old.
- Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
- The subject will have been on insulin pump therapy for at least 3 months.
- Currently using, or willing to switch to Lispro U100 or Aspart for the duration of the study.
- HbA1c < 10%.
Exclusion criteria
- Clinically significant nephropathy, neuropathy (e.g. known or suspected gastroparesis) or retinopathy (e.g. proliferative retinopathy) as judged by the investigator
- Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery
- Anticipated need to use acetaminophen during interventions with the closed-loop system
- Pregnancy (ongoing or current attempt to become pregnant)
- Breastfeeding
- No nearby third party for assistance if needed (e.g. severe hypoglycemia glucagon treatment)
- Plans to go abroad or travel at more than 3 hours distance from Montreal during the trial period
- Severe hypoglycemic episode within two weeks of screening or during the run-in period
- Severe hyperglycemic episode requiring hospitalization in the last 3 months
- Current use of glucocorticoid medication (except low stable dose and inhaled steroids)
- Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, DPP-4 inhibitors) if not at a stable dose for 3 months. Otherwise, these medications are acceptable and will be kept stable during the entire protocol.
- Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months and appropriate ketone testing performed.
- 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
- Anticipation of a significant change in exercise regimen between admission and end of the trial (i.e. starting or stopping an organized sport)
- In the opinion of the investigator, a participant who in unable or unwilling to observed the contraindications of the study devices
Sites / Locations
- Montreal Clinical Research Institute
- McGill University Health Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Carbohydrate counting
Simplified qualitative meal size estimation
Arm Description
Rapid acting insulin analogue with carbohydrate counting
Rapid acting insulin analogue with simplified qualitative meal size estimation
Outcomes
Primary Outcome Measures
Percentage of time of glucose levels spent between 3.9 and 10.0 mmol/L
Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)
Difference between pre-breakfast levels and the lowest glucose level from the start of the exercise until the end of exercise
Secondary Outcome Measures
Percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L
Percentage of time of glucose levels spent below 3.9 mmol/L
Percentage of time of glucose levels spent below 3.3 mmol/L
Percentage of time of glucose levels spent below 2.8 mmol/L
Percentage of time of glucose levels spent above 10.0 mmol/L
Percentage of time of glucose levels spent above 13.9 mmol/L
Percentage of time of glucose levels spent above 16.7 mmol/L
Mean glucose levels
Fasting glucose levels
Standard deviation of glucose levels
Standard deviation of insulin delivery
Coefficient of variance of glucose levels
Coefficient of variance of insulin delivery
Between-day variability in glucose levels
Between-day variability in insulin delivery
Total insulin delivery
Number of hypoglycemic events less than 3.1 mmol/L
Number of nights with hypoglycemic events less than 3.1 mmol/L
Number of days with hypoglycemic events less than 3.1 mmol/L
Total number of hours of sensor availability
Percentage of time of sensor availability
2-hour postprandial glucose levels over the last 3 days of the intervention.
Average number of days per participant requiring study team support for at least one technical problem
Number of hours and percentage of time in open-loop and closed-loop modes
Average number of phone calls per participant related to CLS technical issues
Decrease in plasma glucose levels during exercise (sub-study)
Difference between glucose levels at the beginning of the exercise and the lowest glucose levels from the start of the exercise until the end of exercise
Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)
Difference between pre-breakfast levels and the lowest glucose level from the start of the exercise until the end of exercise
Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent above 13.9 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
Pre-exercise period (from mealtime to exercise onset)
Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
Exercise period
Number of patients experiencing hypoglycemia requiring treatment (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent above 13.3 mmol/L (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
Exercise period
Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
Post-exercise period
Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
Post-exercise period
Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
Post-exercise period
Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
Post-exercise period
Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
Post-exercise period
Percentage of time of plasma glucose levels spent above 13.3 mmol/L (sub-study)
Post-exercise period
Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
Post-exercise period
Number of patients experiencing hypoglycemia requiring treatment (sub-study)
Overall study period
Mean time (minutes) to the first hypoglycemic event (sub-study)
Exercise period
Full Information
NCT ID
NCT04031599
First Posted
July 22, 2019
Last Updated
January 13, 2022
Sponsor
Institut de Recherches Cliniques de Montreal
1. Study Identification
Unique Protocol Identification Number
NCT04031599
Brief Title
Assessment of the Efficacy of the Artificial Pancreas Combined With a Qualitative Meal Size Estimation to Control Postprandial Glucose Levels
Official Title
An Open-label, Randomized, Crossover Trial to Assess the Efficacy of Single-hormone Closed-loop System With a Rapid Acting Insulin Analogue Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation in Regulating Glucose Levels in Adults With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
July 10, 2020 (Actual)
Primary Completion Date
November 27, 2021 (Actual)
Study Completion Date
December 14, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherches Cliniques de Montreal
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Postprandial glycemic excursions are major determinants of overall glycemic control in type 1 diabetes. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels. accurate carbohydrate counting is considered by patients as a significant burden and frustrating task.
The closed-loop system (CLS) is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosages based on the sensor's readings.
The objective of this study is to compare the efficacy of two strategies to regulate glucose levels in outpatient settings in adults with type 1 diabetes: 1) single-hormone CLS with rapid acting insulin analogue combined with carbohydrate counting; 2) single-hormone CLS with rapid acting insulin analogue combined with simplified qualitative meal-size estimation.
A sub-study will also be proposed to participants. Postprandial exercise combines two situations complicating CLS operation: a high plasma insulin due to insulin on-board related to meal boluses and rapid blood glucose changes (postprandial blood glucose excursion and then drop during exercise) making input from the glucose sensor less accurate. The objective of this sub-study will be to explore the safety and efficacy of the CLS using the combined strategy of pre-meal exercise announcement and meal bolus reduction of 33% when exercise is performed 1 hour compared to 2 hours post meal time.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Type 1 diabetes, Artificial pancreas, Closed-loop system, Insulin, Postprandial glucose, Exercise
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carbohydrate counting
Arm Type
Active Comparator
Arm Description
Rapid acting insulin analogue with carbohydrate counting
Arm Title
Simplified qualitative meal size estimation
Arm Type
Active Comparator
Arm Description
Rapid acting insulin analogue with simplified qualitative meal size estimation
Intervention Type
Device
Intervention Name(s)
Single-hormone closed-loop system
Intervention Description
Every 10 minutes, the glucose levels as measured by the sensor will be transferred automatically to a LG Google Nexus Smartphone that the algorithm is running on, which will calculate the recommended doses and will send them wirelessly to the infusion pump.
Intervention Type
Device
Intervention Name(s)
Insulin pump
Intervention Description
Tandem Diabetes Care
Intervention Type
Device
Intervention Name(s)
Continuous glucose monitoring system
Intervention Description
Dexcom G6
Intervention Type
Drug
Intervention Name(s)
Aspart or Lispro
Intervention Description
Aspart or lispro will be infused with the infusion pump
Intervention Type
Other
Intervention Name(s)
Carbohydrate counting
Intervention Description
Participants will be required to enter an estimate of the carbohydrate content of their meal into the phone. Insulin boluses will be calculated based on grams of carbohydrates and participant's insulin-to-carbohydrate ratio. Carbohydrate-matching full prandial bolus will be given 5 to 10 minutes before the meal.
Intervention Type
Other
Intervention Name(s)
Simplified qualitative meal-size estimation strategy
Intervention Description
A pre-meal partial prandial bolus will be given 5-10 minutes before the meal. The partial bolus will be based on the estimated meal size (small, regular, large and extra-large). The closed-loop system will give the remaining insulin needed based on the sensor readings. For this strategy, meal size will be defined as: small as any meal less than 30g, regular meal as any meal between 30g and 60g CHO, large meal as any meal between 60g and 90g CHO, extra-large meal for anything above 90g CHO.
Intervention Type
Other
Intervention Name(s)
3-week intervention
Intervention Description
Glucose levels will be regulated by the single-hormone closed-loop system for 3 consecutive weeks.
Intervention Type
Other
Intervention Name(s)
1-hour postprandial exercise (sub-study)
Intervention Description
60 minute exercise will be started one hour after the meal time.
Intervention Type
Other
Intervention Name(s)
2-hour postprandial exercise (sub-study)
Intervention Description
60 minute exercise will be started two hours after meal time
Intervention Type
Other
Intervention Name(s)
Exercise announcement and meal bolus reduction (sub-study)
Intervention Description
Meal bolus reduction of 33% at meal time and exercise announcement (increased target glucose from 6 to 9mmolL) to the CLS algorithm
Primary Outcome Measure Information:
Title
Percentage of time of glucose levels spent between 3.9 and 10.0 mmol/L
Time Frame
504 hours
Title
Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)
Description
Difference between pre-breakfast levels and the lowest glucose level from the start of the exercise until the end of exercise
Time Frame
3.5 or 4.5 hours
Secondary Outcome Measure Information:
Title
Percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L
Time Frame
504 hours
Title
Percentage of time of glucose levels spent below 3.9 mmol/L
Time Frame
504 hours
Title
Percentage of time of glucose levels spent below 3.3 mmol/L
Time Frame
504 hours
Title
Percentage of time of glucose levels spent below 2.8 mmol/L
Time Frame
504 hours
Title
Percentage of time of glucose levels spent above 10.0 mmol/L
Time Frame
504 hours
Title
Percentage of time of glucose levels spent above 13.9 mmol/L
Time Frame
504 hours
Title
Percentage of time of glucose levels spent above 16.7 mmol/L
Time Frame
504 hours
Title
Mean glucose levels
Time Frame
504 hours
Title
Fasting glucose levels
Time Frame
504 hours
Title
Standard deviation of glucose levels
Time Frame
504 hours
Title
Standard deviation of insulin delivery
Time Frame
504 hours
Title
Coefficient of variance of glucose levels
Time Frame
504 hours
Title
Coefficient of variance of insulin delivery
Time Frame
504 hours
Title
Between-day variability in glucose levels
Time Frame
504 hours
Title
Between-day variability in insulin delivery
Time Frame
504 hours
Title
Total insulin delivery
Time Frame
504 hours
Title
Number of hypoglycemic events less than 3.1 mmol/L
Time Frame
504 hours
Title
Number of nights with hypoglycemic events less than 3.1 mmol/L
Time Frame
126 hours
Title
Number of days with hypoglycemic events less than 3.1 mmol/L
Time Frame
252 hours
Title
Total number of hours of sensor availability
Time Frame
378 hours
Title
Percentage of time of sensor availability
Time Frame
504 hours
Title
2-hour postprandial glucose levels over the last 3 days of the intervention.
Time Frame
18 hours
Title
Average number of days per participant requiring study team support for at least one technical problem
Time Frame
21 days
Title
Number of hours and percentage of time in open-loop and closed-loop modes
Time Frame
504 hours
Title
Average number of phone calls per participant related to CLS technical issues
Time Frame
504 hours
Title
Decrease in plasma glucose levels during exercise (sub-study)
Description
Difference between glucose levels at the beginning of the exercise and the lowest glucose levels from the start of the exercise until the end of exercise
Time Frame
1 hour
Title
Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)
Description
Difference between pre-breakfast levels and the lowest glucose level from the start of the exercise until the end of exercise
Time Frame
2 or 3 hours
Title
Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent above 13.9 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
Description
Pre-exercise period (from mealtime to exercise onset)
Time Frame
1 or 2 hours
Title
Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Number of patients experiencing hypoglycemia requiring treatment (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent above 13.3 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
Description
Exercise period
Time Frame
1 hour
Title
Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Percentage of time of plasma glucose levels spent above 13.3 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
Description
Post-exercise period
Time Frame
1.5 hour
Title
Number of patients experiencing hypoglycemia requiring treatment (sub-study)
Description
Overall study period
Time Frame
3.5 or 4.5 hours
Title
Mean time (minutes) to the first hypoglycemic event (sub-study)
Description
Exercise period
Time Frame
1 hour
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
Males and females ≥ 18 years of old.
Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
The subject will have been on insulin pump therapy for at least 3 months.
Currently using, or willing to switch to Lispro U100 or Aspart for the duration of the study.
HbA1c < 10%.
Exclusion criteria
Clinically significant nephropathy, neuropathy (e.g. known or suspected gastroparesis) or retinopathy (e.g. proliferative retinopathy) as judged by the investigator
Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery
Anticipated need to use acetaminophen during interventions with the closed-loop system
Pregnancy (ongoing or current attempt to become pregnant)
Breastfeeding
No nearby third party for assistance if needed (e.g. severe hypoglycemia glucagon treatment)
Plans to go abroad or travel at more than 3 hours distance from Montreal during the trial period
Severe hypoglycemic episode within two weeks of screening or during the run-in period
Severe hyperglycemic episode requiring hospitalization in the last 3 months
Current use of glucocorticoid medication (except low stable dose and inhaled steroids)
Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, DPP-4 inhibitors) if not at a stable dose for 3 months. Otherwise, these medications are acceptable and will be kept stable during the entire protocol.
Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months and appropriate ketone testing performed.
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
Anticipation of a significant change in exercise regimen between admission and end of the trial (i.e. starting or stopping an organized sport)
In the opinion of the investigator, a participant who in unable or unwilling to observed the contraindications of the study devices
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rémi Rabasa-Lhoret
Organizational Affiliation
Montreal Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montreal Clinical Research Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada
Facility Name
McGill University Health Center
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Assessment of the Efficacy of the Artificial Pancreas Combined With a Qualitative Meal Size Estimation to Control Postprandial Glucose Levels
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