Closed-loop Control of Glucose Levels (Artificial Pancreas) for 5 Days in Adults With Type 1 Diabetes

Condition(s) targeted: Type 1 Diabetes

Intervention: 5-day intervention with single-hormone closed-loop strategy (Other); 5-day intervention with sensor-augmented pump therapy (Other); 5-day intervention with dual-hormone closed-loop strategy (Other); Insulin pump (Device); Continuous glucose monitoring system (Device); Insulin (Drug); Glucagon (Drug)

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, MD, PhD, Principal Investigator, Affiliation: Institut de recherches cliniques de Montréal

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

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 strategy would regulate glucose levels through the infusion of two hormones: 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 sensor-augmented pump therapy to regulate glucose levels in outpatient settings for 5 consecutive days in adults with type 1 diabetes. The investigators hypothesized that dual-hormone closed-loop strategy will reduce the time spent in hypoglycemia compared to single-hormone closed-loop strategy, which in turn will be more effective than sensor-augmented pump therapy to reduce time spent in hypoglycemia.

Official title: An Open-label, Randomized, Three-way, Cross-over Study to Assess the Efficacy of Single-hormone Closed-loop Strategy, Dual-hormone Closed-loop Strategy and Sensor-augmented Pump Therapy in Regulating Glucose Levels for 5 Days in Free-living Outpatient Conditions in Patients With Type 1 Diabetes

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

Primary outcome: Percentage of time of glucose levels spent below 4.0 mmol/L

Secondary outcome:

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

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

Percentage of time of glucose levels spent below 3.5 mmol/L

Percentage of time of glucose levels spent below 3.3 mmol/L

Percentage of time of glucose levels spent above 8.0 mmol/L

Percentage of time of glucose levels spent above 10.0 mmol/L

Percentage of time of glucose levels spent above 15.0 mmol/L

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

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

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

Percentage of time of overnight glucose levels spent below 3.5 mmol/L

Percentage of time of overnight glucose levels spent below 3.3 mmol/L

Percentage of time of overnight glucose levels spent above 8.0 mmol/L

Percentage of time of overnight glucose levels spent above 10.0 mmol/L

Percentage of time of overnight glucose levels spent above 15.0 mmol/L

Area under the curve of glucose levels below 4.0 mmol/L

Area under the curve of glucose levels below 3.5 mmol/L

Area under the curve of glucose levels below 3.3 mmol/L

Area under the curve of glucose levels above 8.0 mmol/L

Area under the curve of glucose levels above 10.0 mmol/L

Area under the curve of glucose levels above 15.0 mmol/L

Area under the curve of overnight glucose levels below 4.0 mmol/L

Area under the curve of overnight glucose levels below 3.5 mmol/L

Area under the curve of overnight glucose levels below 3.3 mmol/L

Area under the curve of overnight glucose levels above 8.0 mmol/L

Area under the curve of overnight glucose levels above 10.0 mmol/L

Area under the curve of overnight glucose levels above 15.0 mmol/L

Mean glucose levels

Standard deviation of glucose levels

Standard deviation of insulin delivery

Coefficient of variance of glucose levels

Coefficient of variance of insulin delivery

Between-day variability in glucose levels

Between-day variability in insulin delivery

Between-day variability in glucagon delivery

Total insulin delivery

Total glucagon delivery

Percentage of time of closed-loop operation

Percentage of time of glucose sensor availability

Time between failures

Number of hypoglycemic events less than 3.1 mmol/L

Number of nights with hypoglycemic events less than 3.1 mmol/L

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

Criteria:

Inclusion Criteria: 1. Males and females ≥ 18 years of 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. 4. HbA1c ≤ 10%. Exclusion Criteria: 1. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator. 2. Recent (< 6 months) acute macrovascular event e. g. acute coronary syndrome or cardiac surgery. 3. History of pheochromocytoma or insulinoma (glucagon could induce a hormonal response of these tumors) 4. Beta‐blockers at high dose based on investigator's evaluation of dosage interference with glucagon (glucagon can modify effect of beta-blockers, mostly evident at very high doses) 5. Chronic indometacin treatment (can prevent glucagon effect on liver thus its ability to raise glucose) 6. Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding) 7. Anticholenergic drug (risk of interaction) 8. Pregnancy. 9. Severe hypoglycemic episode within two weeks of screening. 10. Current use of glucocorticoid medication (except low stable dose and inhaled steroids). 11. Known or suspected allergy to the trial products 12. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator. 13. Anticipating a significant change in exercise regimen between admissions (i. e. starting or stopping an organized sport). 14. Treatments that could interfere with glucagon

Virginie Messier, MSc, 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, MSc, Phone: 514-987-5500, Ext: 3227, Email: virginie.messier@ircm.qc.ca
Rémi Rabasa-Lhoret, MD, PhD, Principal Investigator

Starting date: September 2015
Last updated: June 30, 2015