Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sensor-augmented pump therapy | Active Comparator | Patients will use conventional pump therapy and freely implement their usual basal rate and CHO-matching full prandial bolus to regulate glucose levels. |
|
| Single-hormone CLS with full boluses | Active Comparator | 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. |
|
| Single-hormone CLS with partial boluses | Active Comparator | 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. |
|
| Dual-hormone CLS with full boluses | Active Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 15-hour intervention | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 15 hours |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 15 hours |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Rémi Rabasa-Lhoret | Institut de Recherches Cliniques de Montreal | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut de recherches cliniques de Montréal | Montreal | Quebec | H2W1R7 | Canada |
Not provided
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D007333 | Insulin Resistance |
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008722 | Methods |
| D007328 | Insulin |
| D061268 | Insulin Lispro |
| D061267 | Insulin Aspart |
| D005934 | Glucagon |
| ID | Term |
|---|---|
| D008919 | Investigative Techniques |
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Dual-hormone CLS with partial boluses | Active Comparator | 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. |
|
|
| Insulin (Lispro, Aspart or guilisine) | Drug | Patient's usual insulin (Lispro, Aspart or guilisine) will be used in all interventions. |
|
| Glucagon (Eli Lilly) | Drug | In the dual-hormone CLS interventions, glucagon (Eli Lilly) will be used. |
|
| Closed-loop strategy | Other | 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. |
|
| Percentage of time of sensor glucose concentrations between 4 and 8 mmol/L | 15 hours |
| Percentage of time of sensor glucose concentrations between 4 and 10 mmol/L | 15 hours |
| Percentage of time of sensor glucose concentrations above 10 mmol/L | 15 hours |
| Percentage of time of sensor glucose concentrations above 14 mmol/L | 15 hours |
| Percentage of time of glucose levels spent below 4 mmol/L | 15 hours |
| Percentage of time of glucose levels spent below 3.1 mmol/L | 15 hours |
| Area under the curve of glucose values below 4 mmol/L | 15 hours |
| Area under the curve of glucose values below 3.1 mmol/L | 15 hours |
| Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms | 15 hours |
| Total number of hypoglycemic event below 3.1 mmol/L | 15 hours |
| Total insulin delivery | 15 hours |
| Total glucagon delivery | 15 hours |
| Standard deviation of glucose levels | 15 hours |
| Total carbohydrate intake | 15 hours |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
| D036361 |
| Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061266 | Insulin, Short-Acting |
| D052336 | Proglucagon |