Closed-loop Control of Glucose Levels (Artificial Pancreas) for 24 Hours in Adults and Adolescents With Type 1 Diabetes

Phase 2

Completed

Brief Summary: Closed-loop strategy 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. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormone: insulin and glucagon.

The main objective of this project is to compare the efficacy of single-hormone closed-loop strategy, dual-hormone closed-loop strategy and pump therapy to regulate glucose levels in a 24-hours in-patient study with standardized conditions in adults and adolescents with type 1 diabetes.

The investigators hypothesized that dual-hormone closed-loop strategy is more effective in regulating glucose levels in adults and adolescents with type 1 diabetes compared to single-hormone closed-loop strategy, which in turn is more effective than the conventional pump therapy.

Detailed Description: Closed-loop strategy 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. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormone: insulin and glucagon.

We aim to conduct the 1st randomized three-way cross-over trial comparing single hormone closed-loop strategy, dual-hormone closed-loop strategy and the conventional pump therapy. We aim to compare the three interventions for 24 hours in adults and adolescents with type 1 diabetes. Each 24 hours will include a 60-min exercise session, three meals characterizing a full day, activities that mimick real-life conditions and an overnight stay. This study will also allow for multiple comparisons and evaluating the benefits of each component separately (i.e. the benefits of merely closing the loop with insulin alone vs. adding glucagon to the closed-loop strategy).

Recruitment & Eligibility

Inclusion Criteria

Males and females ≥ 12 years of old.
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.
The subject will have been on insulin pump therapy for at least 3 months.
HbA1c ≤ 12%.

Exclusion Criteria

Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
A recent injury to body or limb, muscular disorder, use of any medication or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the exercise protocol.
Pregnancy.
Severe hypoglycemic episode within two weeks of screening.
Current use of glucocorticoid medication (except low stable dose).
Known or suspected allergy to the trial products or meal contents.
Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc).

Arm && Interventions

Group	Intervention	Description
Dual-hormone closed-loop system	Closed-loop system	In dual-hormone closed-loop system, variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels.
Insulin pump therapy	Closed-loop system	Patient's conventional treatment will be implemented.
Single-hormone closed-loop system	Closed-loop system	In single-hormone closed-loop system, variable subcutaneous insulin infusion rate will be used to regulate glucose levels.

Primary Outcome Measures

Name	Time	Method
Percentage of time of plasma glucose levels spent in target range.	24 hours	Two-hour postprandial target range is between 4.0 and 10.0 mmol/l. Otherwise, target range is defined to be between 4.0 and 8.0 mmol/l.

Secondary Outcome Measures

Name	Time	Method
Percentage of time of plasma glucose levels spent in the low range	24 hours	Low range is defined to be a. below 4 mmol/L; b. below 3.5 mmol/L; c. below 3.3 mmol/L.
Total insulin delivery	24 hours
Percentage of overnight time of plasma glucose levels spent between 4.0 and 8.0 mmol/L	9 hours
Percentage of time of plasma glucose levels spent in the high range	24 hours	High range is defined to be above a. 8.0 mmol/L; b. 10.0 mmol/L
Mean plasma insulin concentration	24 hours
Number of subjects experiencing hypoglycemia requiring oral treatment	24 hours	Number of subjects experiencing hypoglycemia requiring oral treatment during a. the overall study period; b. the exercise; c. the night.
Percentage of overnight time of plasma glucose levels spent in the low range	9 hours	Low range is defined to be a. \< 4 mmol/L; b. \< 3.5 mmol/L; c. \< 3.3 mmol/L.
Mean plasma glucagon concentration	24 hours
Percentage of overnight time of plasma glucose levels spent between 4.0 and 10.0 mmol/L	9 hours
Standard deviation of glucose levels	24 hours	Measure of glucose variability
Mean plasma glucose level	9 hours
Percentage of time of plasma glucose levels spent between 4.0 and 10.0 mmol/L	24 hours
Percentage of overnight time of plasma glucose levels spent in the high range	9 hours	High range is defined to be above a. 8.0 mmol/L; b. 10.0 mmol/L.

Locations (1): Institut de recherches cliniques de Montréal
🇨🇦
Montreal, Quebec, Canada