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

Condition(s) targeted: Type 1 Diabetes

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

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Institut de Recherches Cliniques de Montreal

Official(s) and/or principal investigator(s):
Rémi Rabasa-Lhoret, Principal Investigator, Affiliation: Institut de recherches cliniques de Montréal

Overall contact:
Virginie Messier, Phone: 514-987-5500, Ext: 3227, Email: virginie.messier@ircm.qc.ca

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;

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 Children and Adults With Type 1 Diabetes

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mean day-and-night glucose levels

Secondary outcome:

Percentage of time of glucose levels between 4.0 and 8.0 mmol/L

Percentage of time of glucose levels between 4.0 and 10.0 mmol/L

Percentage of time of glucose levels above 10.0 mmol/L

Percentage of time of glucose levels above 14.0 mmol/L

Percentage of time of glucose levels spent below 4.0 mmol/L

Percentage of time of glucose levels spent below 3.1 mmol/L

Area under the curve of glucose values below 4.0 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

Minimum age: 8 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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. 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.

Virginie Messier, Phone: 514-987-5500, Ext: 3227, Email: virginie.messier@ircm.qc.ca

Institut de recherches cliniques de Montréal, Montreal, Quebec H2W 1R7, Canada; Not yet recruiting
Virginie Messier, Phone: 514-987-5500, Ext: 3227, Email: virginie.messier@ircm.qc.ca
Rémi Rabasa-Lhoret, Principal Investigator

Starting date: October 2015
Last updated: July 2, 2015