Back to resultsClosed-loop Control of Postprandial Glucose Levels in Adults With Type 1 Diabetes
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
15-hour intervention
Insulin (Lispro, Aspart or guilisine)
Glucagon (Eli Lilly)
Closed-loop strategy
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Closed-loop strategy, Artificial pancreas, Postprandial glucose, Insulin, Glucagon, Hypoglycemia, Type 1 diabetes
Eligibility Criteria
Inclusion Criteria:
- Males and females ≥ 18 years old.
- Clinical diagnosis of type 1 diabetes for at least one year.
- The subject will have been on insulin pump therapy for at least 3 months and currently using a fast actin insulin analog (Lispro, Aspart or Guilisine).
- Last (less than 3 months) HbA1c ≤ 10%.
- Currently using carbohydrate counting as the meal insulin dose strategy.
Exclusion Criteria:
- Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator.
- Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
- Ongoing pregnancy.
- Severe hypoglycemic episode within 1 month of screening.
- Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, SGLT-2 inhibitors and 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.
- Oral steroids unless patients present a low stable dose (e.g. 10 mg or less of prednisone per day or physiological doses, less than 35 mg/day, of hydrocortisone Cortef®). Inhale steroids at stable dose in the last month are acceptable.
- Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator (e.g. unstable psychiatric condition).
- Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).
- Living or planned travel outside Montreal (> 1h of driving) area during closed-loop procedures.
Sites / Locations
- Institut de recherches cliniques de Montréal
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Sensor-augmented pump therapy
Single-hormone CLS with full boluses
Single-hormone CLS with partial boluses
Dual-hormone CLS with full boluses
Dual-hormone CLS with partial boluses
Arm Description
Patients will use conventional pump therapy and freely implement their usual basal rate and CHO-matching full prandial bolus to regulate glucose levels.
Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Carbohydrate-matching full prandial bolus will be given 10 minutes before the meal. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.
Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. A pre-meal partial prandial bolus will be given 10 minutes before the meal. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). Meal size will be defined as: snack 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, very large meal for anything above 90g CHO.
Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Carbohydrate-matching full prandial bolus will be given 10 minutes before the meal. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.
Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. A pre-meal partial prandial bolus will be given 10 minutes before the meal. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). Meal size will be defined as: snack 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, very large meal for anything above 90g CHO.
Outcomes
Primary Outcome Measures
Mean glucose levels as measured by the glucose sensor.
The following comparisons will be done: 1) Dual-hormone CLS with partial boluses vs. dual-hormone CLS with full boluses; 2) Single-hormone CLS with partial boluses vs. single-hormone CLS with full boluses.
Secondary Outcome Measures
Mean glucose levels as measured by the glucose sensor
The following comparisons will be done: 1) Dual-hormone CLS with partial boluses vs. single-hormone CLS with partial boluses; 2) Dual-hormone CLS with partial boluses vs. sensor-augmented pump therapy; 3) Single-hormone CLS with partial boluses vs. sensor-augmented pump therapy.
Percentage of time of sensor glucose concentrations between 4 and 8 mmol/L
Percentage of time of sensor glucose concentrations between 4 and 10 mmol/L
Percentage of time of sensor glucose concentrations above 10 mmol/L
Percentage of time of sensor glucose concentrations above 14 mmol/L
Percentage of time of glucose levels spent below 4 mmol/L
Percentage of time of glucose levels spent below 3.1 mmol/L
Area under the curve of glucose values below 4 mmol/L
Area under the curve of glucose values below 3.1 mmol/L
Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms
Total number of hypoglycemic event below 3.1 mmol/L
Total insulin delivery
Total glucagon delivery
Standard deviation of glucose levels
Total carbohydrate intake
Full Information
NCT ID
NCT02416765
First Posted
April 2, 2015
Last Updated
November 13, 2015
Sponsor
Institut de Recherches Cliniques de Montreal
1. Study Identification
Unique Protocol Identification Number
NCT02416765
Brief Title
Closed-loop Control of Postprandial Glucose Levels in Adults With Type 1 Diabetes
Official Title
An Open-label, Randomized, Five-way, Cross-over Study to Compare the Efficacy of Single- and Dual-hormone Closed-loop Operations Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation, and Sensor-augmented Pump Therapy in Regulating Glucose Levels in Adults With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherches Cliniques de Montreal
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Postprandial meal glucose control with closed-loop systems (CLS) still needs some improvements. In the postprandial period, sensor delay in detecting blood glucose rise after a meal together with delays in insulin absorption expose patients to early risk of hyperglycemia and then to late-postprandial hypoglycemia. Glucagon infusion in dual-hormone CLS has the potential to improve post-meal control as compared to single-hormone CLS allowing a better glucose excursion related to a more aggressive insulin infusion while minimizing hypoglycemic risk. Several approaches have been tested for the determination of prandial boluses during closed-loop operation.
The objective of this study is to test in outpatient unrestricted settings whether, in the context of closed-loop strategy, conventional meal carbohydrate counting could be reduced to a simplified qualitative meal size estimation without a significant degradation in overall glycemic control in adult patients with type 1 diabetes.
The investigators hypothesize that in outpatient free-living conditions: 1) Dual-hormone CLS with partial boluses is equivalent to dual-hormone CLS with full boluses in terms of mean glucose; 2) Single-hormone CLS with partial boluses is equivalent to single-hormone CLS with full boluses in terms of mean glucose. Secondary hypothesis are: 3) Dual-hormone CLS with partial boluses will decrease time in hypoglycemia compared to single-hormone CLS with partial boluses; 4) Dual-hormone CLS with partial boluses is better than sensor-augmented pump therapy in terms of mean glucose; 5) Single-hormone CLS with partial boluses is better than sensor-augmented pump therapy in terms of mean glucose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Closed-loop strategy, Artificial pancreas, Postprandial glucose, Insulin, Glucagon, Hypoglycemia, Type 1 diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sensor-augmented pump therapy
Arm Type
Active Comparator
Arm Description
Patients will use conventional pump therapy and freely implement their usual basal rate and CHO-matching full prandial bolus to regulate glucose levels.
Arm Title
Single-hormone CLS with full boluses
Arm Type
Active Comparator
Arm Description
Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Carbohydrate-matching full prandial bolus will be given 10 minutes before the meal. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.
Arm Title
Single-hormone CLS with partial boluses
Arm Type
Active Comparator
Arm Description
Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. A pre-meal partial prandial bolus will be given 10 minutes before the meal. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). Meal size will be defined as: snack 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, very large meal for anything above 90g CHO.
Arm Title
Dual-hormone CLS with full boluses
Arm Type
Active Comparator
Arm Description
Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Carbohydrate-matching full prandial bolus will be given 10 minutes before the meal. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.
Arm Title
Dual-hormone CLS with partial boluses
Arm Type
Active Comparator
Arm Description
Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. A pre-meal partial prandial bolus will be given 10 minutes before the meal. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). Meal size will be defined as: snack 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, very large meal for anything above 90g CHO.
Intervention Type
Other
Intervention Name(s)
15-hour intervention
Intervention Description
Interventions will be conducted in outpatient settings. Subject's usual insulin will be used. Meals will not be standardized. Subjects will be allowed to eat whatever and when they want and will be allowed to drink alcohol. Subjects will be allowed to exercise, but they will be asked to do the same amount and intensity of exercise on all intervention visits. Subjects will be accompanied all the time by a member from the research team during closed-loop visits to implement hormonal infusions.
Intervention Type
Drug
Intervention Name(s)
Insulin (Lispro, Aspart or guilisine)
Intervention Description
Patient's usual insulin (Lispro, Aspart or guilisine) will be used in all interventions.
Intervention Type
Drug
Intervention Name(s)
Glucagon (Eli Lilly)
Intervention Description
In the dual-hormone CLS interventions, glucagon (Eli Lilly) will be used.
Intervention Type
Other
Intervention Name(s)
Closed-loop strategy
Intervention Description
Every 10 minutes, the glucose level as measured by the real time sensor (Dexcom G4 Platinum, Dexcom) will be entered manually into the computer. The pumps' infusion rate will then be changed manually based on the computer generated recommendation infusion rates. The computer generated recommendations are based on a predictive algorithm.
Primary Outcome Measure Information:
Title
Mean glucose levels as measured by the glucose sensor.
Description
The following comparisons will be done: 1) Dual-hormone CLS with partial boluses vs. dual-hormone CLS with full boluses; 2) Single-hormone CLS with partial boluses vs. single-hormone CLS with full boluses.
Time Frame
15 hours
Secondary Outcome Measure Information:
Title
Mean glucose levels as measured by the glucose sensor
Description
The following comparisons will be done: 1) Dual-hormone CLS with partial boluses vs. single-hormone CLS with partial boluses; 2) Dual-hormone CLS with partial boluses vs. sensor-augmented pump therapy; 3) Single-hormone CLS with partial boluses vs. sensor-augmented pump therapy.
Time Frame
15 hours
Title
Percentage of time of sensor glucose concentrations between 4 and 8 mmol/L
Time Frame
15 hours
Title
Percentage of time of sensor glucose concentrations between 4 and 10 mmol/L
Time Frame
15 hours
Title
Percentage of time of sensor glucose concentrations above 10 mmol/L
Time Frame
15 hours
Title
Percentage of time of sensor glucose concentrations above 14 mmol/L
Time Frame
15 hours
Title
Percentage of time of glucose levels spent below 4 mmol/L
Time Frame
15 hours
Title
Percentage of time of glucose levels spent below 3.1 mmol/L
Time Frame
15 hours
Title
Area under the curve of glucose values below 4 mmol/L
Time Frame
15 hours
Title
Area under the curve of glucose values below 3.1 mmol/L
Time Frame
15 hours
Title
Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms
Time Frame
15 hours
Title
Total number of hypoglycemic event below 3.1 mmol/L
Time Frame
15 hours
Title
Total insulin delivery
Time Frame
15 hours
Title
Total glucagon delivery
Time Frame
15 hours
Title
Standard deviation of glucose levels
Time Frame
15 hours
Title
Total carbohydrate intake
Time Frame
15 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females ≥ 18 years old.
Clinical diagnosis of type 1 diabetes for at least one year.
The subject will have been on insulin pump therapy for at least 3 months and currently using a fast actin insulin analog (Lispro, Aspart or Guilisine).
Last (less than 3 months) HbA1c ≤ 10%.
Currently using carbohydrate counting as the meal insulin dose strategy.
Exclusion Criteria:
Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator.
Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
Ongoing pregnancy.
Severe hypoglycemic episode within 1 month of screening.
Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, SGLT-2 inhibitors and 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.
Oral steroids unless patients present a low stable dose (e.g. 10 mg or less of prednisone per day or physiological doses, less than 35 mg/day, of hydrocortisone Cortef®). Inhale steroids at stable dose in the last month are acceptable.
Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator (e.g. unstable psychiatric condition).
Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).
Living or planned travel outside Montreal (> 1h of driving) area during closed-loop procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rémi Rabasa-Lhoret
Organizational Affiliation
Institut de recherches cliniques de Montréal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut de recherches cliniques de Montréal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W1R7
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Closed-loop Control of Postprandial Glucose Levels in Adults With Type 1 Diabetes
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