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

Condition(s) targeted: Type 1 Diabetes

Intervention: 15-hour intervention (Other); Insulin (Lispro, Aspart or guilisine) (Drug); Glucagon (Eli Lilly) (Drug); Closed-loop strategy (Other)

Phase: Phase 2

Status: 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:
Véronique Gingras, Phone: 514-987-5500, Ext: 3238, Email: veronique.gingras@ircm.qc.ca

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.

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

Primary outcome: Mean glucose levels as measured by the glucose sensor.

Secondary outcome:

Mean glucose levels as measured by the glucose sensor

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Males and females ≥ 18 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. Ongoing 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.

Véronique Gingras, Phone: 514-987-5500, Ext: 3238, Email: veronique.gingras@ircm.qc.ca

Institut de recherches cliniques de Montréal, Montreal, Quebec H2W1R7, Canada; Recruiting
Véronique Gingras, Phone: 514-987-5000, Ext: 3238, Email: veronique.gingras@ircm.qc.ca

Starting date: May 2015
Last updated: May 1, 2015