Assessment of the Efficacy of the Artificial Pancreas Combined With a Qualitative Meal Size Estimation to Control Postprandial Glucose Levels

An Open-label, Randomized, Crossover Trial to Assess the Efficacy of Single-hormone Closed-loop System With a Rapid Acting Insulin Analogue Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation in Regulating Glucose Levels in Adults With Type 1 Diabetes

Postprandial glycemic excursions are major determinants of overall glycemic control in type 1 diabetes. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels. accurate carbohydrate counting is considered by patients as a significant burden and frustrating task.

The closed-loop system (CLS) is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosages based on the sensor's readings.

The objective of this study is to compare the efficacy of two strategies to regulate glucose levels in outpatient settings in adults with type 1 diabetes: 1) single-hormone CLS with rapid acting insulin analogue combined with carbohydrate counting; 2) single-hormone CLS with rapid acting insulin analogue combined with simplified qualitative meal-size estimation.

A sub-study will also be proposed to participants. Postprandial exercise combines two situations complicating CLS operation: a high plasma insulin due to insulin on-board related to meal boluses and rapid blood glucose changes (postprandial blood glucose excursion and then drop during exercise) making input from the glucose sensor less accurate. The objective of this sub-study will be to explore the safety and efficacy of the CLS using the combined strategy of pre-meal exercise announcement and meal bolus reduction of 33% when exercise is performed 1 hour compared to 2 hours post meal time.

Inclusion criteria

1. Males and females ≥ 18 years of old.
2. Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
3. The subject will have been on insulin pump therapy for at least 3 months.
4. Currently using, or willing to switch to Lispro U100 or Aspart for the duration of the study.
5. HbA1c < 10%.

Exclusion criteria

1. Clinically significant nephropathy, neuropathy (e.g. known or suspected gastroparesis) or retinopathy (e.g. proliferative retinopathy) as judged by the investigator
2. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery
3. Anticipated need to use acetaminophen during interventions with the closed-loop system
4. Pregnancy (ongoing or current attempt to become pregnant)
5. Breastfeeding
6. No nearby third party for assistance if needed (e.g. severe hypoglycemia glucagon treatment)
7. Plans to go abroad or travel at more than 3 hours distance from Montreal during the trial period
8. Severe hypoglycemic episode within two weeks of screening or during the run-in period
9. Severe hyperglycemic episode requiring hospitalization in the last 3 months
10. Current use of glucocorticoid medication (except low stable dose and inhaled steroids)
11. Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, 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.
12. Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months and appropriate ketone testing performed.
13. Known or suspected allergy to the trial products
14. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator
15. Anticipation of a significant change in exercise regimen between admission and end of the trial (i.e. starting or stopping an organized sport)
16. In the opinion of the investigator, a participant who in unable or unwilling to observed the contraindications of the study devices