Closed-loop Control of Postprandial Glucose Levels in Children and Adults With Type 1 Diabetes

Institut de Recherches Cliniques de Montreal

Status and phase: Withdrawn; Phase 2

Conditions: Type 1 Diabetes

Treatments: Drug: Glucagon; Device: Insulin pump MiniMed® Paradigm® Veo™, Medtronic; Drug: Insulin; Other: 6-day intervention with single-hormone closed-loop strategy; Device: Continuous Glucose Monitoring System Enlite sensor®, Medtronic; Other: 6-day intervention with sensor-augmented pump therapy; Other: 6-day intervention with dual-hormone closed-loop strategy

Study type: Interventional

Funder types: Other

Identifiers

NCT02490098

CLASS-13

Details and patient eligibility

About

Current intensive insulin therapy in T1D involves prandial insulin boluses depending on the carbohydrate content of each ingested meal. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Therefore, accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels in type 1 diabetes in order to avoid too much or too little insulin resulting in hypoglycemia and hyperglycemia, respectively. Precision of carbohydrate counting is associated with better glycemic control. However, accurate carbohydrate counting is a challenging task for many patients with type 1 diabetes. Recent developments of continuous glucose sensors and insulin infusion pumps have motivated the research toward "closed-loop'' strategies to regulate glucose levels in patients with type 1 diabetes. In a closed-loop strategy, the pump insulin infusion rate is altered based on a computer generated recommendation that rely on continuous glucose sensor readings. A dual-hormone closed-loop strategy has also been recently proposed to regulate glucose levels. In a dual-hormone strategy, subcutaneous insulin delivery is accompanied by subcutaneous glucagon infusion. Postprandial meal glucose control with closed-loop strategy still needs some improvements. 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 children and adult patients with type 1 diabetes. The investigators hypothesize that 1) dual-hormone closed-loop strategy with qualitative meal size estimation is equivalent to dual-hormone closed-loop strategy with CHO counting in terms of mean glucose; 2) single-hormone closed-loop strategy with qualitative meal size estimation is equivalent to single-hormone closed-loop strategy with CHO counting in terms of mean glucose;

Sex: All

Ages: 8+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males and females ≥ 8 years old.
2. Clinical diagnosis of type 1 diabetes for at least one year.
3. 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).
4. Last (less than 3 months) HbA1c ≤ 10%.
5. Currently using carbohydrate counting as the meal insulin dose strategy.
6. Live in the area of Montreal

Exclusion criteria

1. 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.
2. Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
3. Pregnancy.
4. Severe hypoglycemic episode within 1 month of screening.
5. 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.
6. 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.
7. 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).
8. Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).
9. Living or planned travel outside Montreal (> 1h of driving) area during closed-loop procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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0 participants in 5 patient groups

Single-hormone closed-loop strategy with full boluses

Active Comparator group

Description:

Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.

Treatment:

Device: Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Device: Insulin pump MiniMed® Paradigm® Veo™, Medtronic

Drug: Insulin

Other: 6-day intervention with single-hormone closed-loop strategy

Dual-hormone closed-loop strategy with full boluses

Active Comparator group

Description:

Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) and Glucagon (Eli Lilly) will be infused using two separate subcutaneous infusion pumps (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.

Treatment:

Drug: Glucagon

Device: Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Other: 6-day intervention with dual-hormone closed-loop strategy

Device: Insulin pump MiniMed® Paradigm® Veo™, Medtronic

Drug: Insulin

Single-hormone closed-loop strategy with partial boluses

Active Comparator group

Description:

Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). For this strategy, 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. The meal size assessment will be done by the patient.

Treatment:

Device: Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Device: Insulin pump MiniMed® Paradigm® Veo™, Medtronic

Drug: Insulin

Other: 6-day intervention with single-hormone closed-loop strategy

Dual-hormone closed-loop strategy with partial boluses

Active Comparator group

Description:

Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Guilisine) and Glucagon (Eli Lilly) will be infused using two separate subcutaneous infusion pumps (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). For this strategy, 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. The meal size assessment will be done by the patient.

Treatment:

Drug: Glucagon

Device: Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Other: 6-day intervention with dual-hormone closed-loop strategy

Device: Insulin pump MiniMed® Paradigm® Veo™, Medtronic

Drug: Insulin

Sensor-augmented pump therapy

Active Comparator group

Description:

Subjects will use sensor-augmented pump therapy and freely implement their usual basal rate and CHO-matching full prandial bolus to regulate glucose levels. Patient's usual fast acting insulin analog will be infused using a subcutaneous insulin infusion pump. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.

Treatment:

Device: Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Other: 6-day intervention with sensor-augmented pump therapy

Device: Insulin pump MiniMed® Paradigm® Veo™, Medtronic

Drug: Insulin