Closed-loop Control of Glucose Levels (Artificial Pancreas) for 15 Weeks in Adolescents and Adults With Type 1 Diabetes

Phase 2

Withdrawn

Conditions: Type 1 Diabetes

Interventions: Other: 15-week intervention with sensor-augmented pump
Other: 15-week intervention with single-hormone closed-loop
Other: 15-week intervention with dual-hormone closed-loop
Device: Insulin pump
Device: Continuous glucose monitoring system
Drug: Insulin
Drug: Glucagon

Registration Number: NCT02846857

Lead Sponsor: Institut de Recherches Cliniques de Montreal

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 strategy regulates glucose levels through the infusion of two hormones: insulin and glucagon.

The objective of this study is to compare, in a randomized multicenter trial, the effectiveness of single-hormone closed-loop, dual-hormone closed-loop, and sensor-augmented pump therapy with low-glucose suspend in regulating day-and-night glucose levels in outpatient settings for 15 weeks in adolescents and adults.

The investigators hypothesize that dual-hormone closed-loop will reduce time spent in hypoglycemia compared to single-hormone closed-loop, which in turn will be more effective than sensor-augmented pump therapy with low-glucose suspend.

Detailed Description: Not available

Recruitment & Eligibility

Status: WITHDRAWN

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Males and females ≥ 12 years of old.
Clinical diagnosis of type 1 diabetes for at least one year.
The subject will have been on insulin pump therapy for at least 3 months.
HbA1c ≤ 11%.

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.
History of pheochromocytoma or insulinoma (glucagon could induce a hormonal response of these tumors)
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)
Chronic indometacin treatment (can prevent glucagon effect on liver thus its ability to raise glucose)
Chronic acetaminophen treatment (can interfere with glucose sensor measurements)
Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding)
Anticholinergic drug (risk of interaction)
Pregnancy.
Severe hypoglycemic episode within two weeks of screening.
Current use of glucocorticoid medication (except low stable dose and inhaled steroids).
Known or suspected allergy to the trial products
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).
Treatments that could interfere with glucagon

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sensor-augmented pump therapy	15-week intervention with sensor-augmented pump	Participants will use sensor-augmented pump therapy with low-glucose suspend to regulate glucose levels. The low-glucose suspend feature available in the MiniMed® Paradigm® Veo™, Medtronic combined with the Enlite sensor® will be used. This feature allows for suspension of insulin delivery at a pre-set sensor glucose value for up to 2 hours.
Sensor-augmented pump therapy	Insulin pump	Participants will use sensor-augmented pump therapy with low-glucose suspend to regulate glucose levels. The low-glucose suspend feature available in the MiniMed® Paradigm® Veo™, Medtronic combined with the Enlite sensor® will be used. This feature allows for suspension of insulin delivery at a pre-set sensor glucose value for up to 2 hours.
Sensor-augmented pump therapy	Continuous glucose monitoring system	Participants will use sensor-augmented pump therapy with low-glucose suspend to regulate glucose levels. The low-glucose suspend feature available in the MiniMed® Paradigm® Veo™, Medtronic combined with the Enlite sensor® will be used. This feature allows for suspension of insulin delivery at a pre-set sensor glucose value for up to 2 hours.
Sensor-augmented pump therapy	Insulin	Participants will use sensor-augmented pump therapy with low-glucose suspend to regulate glucose levels. The low-glucose suspend feature available in the MiniMed® Paradigm® Veo™, Medtronic combined with the Enlite sensor® will be used. This feature allows for suspension of insulin delivery at a pre-set sensor glucose value for up to 2 hours.
Single-hormone closed-loop strategy	15-week intervention with single-hormone closed-loop	Variable subcutaneous insulin infusion will be used to regulate glucose levels. Participant's usual fast-acting insulin analog will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump.
Single-hormone closed-loop strategy	Insulin pump	Variable subcutaneous insulin infusion will be used to regulate glucose levels. Participant's usual fast-acting insulin analog will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump.
Single-hormone closed-loop strategy	Continuous glucose monitoring system	Variable subcutaneous insulin infusion will be used to regulate glucose levels. Participant's usual fast-acting insulin analog will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump.
Dual-hormone closed-loop strategy	15-week intervention with dual-hormone closed-loop	Variable subcutaneous insulin and glucagon mini-boluses will be infused using two separate subcutaneous infusion pumps to regulate glucose levels (MiniMed® Paradigm® Veo™, Medtronic). Participant's usual fast-acting insulin analog and Glucagon (Eli Lilly) will be used. Every 10 minutes, the glucose level as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Newly reconstituted glucagon will be used every 24 hours.
Dual-hormone closed-loop strategy	Insulin pump	Variable subcutaneous insulin and glucagon mini-boluses will be infused using two separate subcutaneous infusion pumps to regulate glucose levels (MiniMed® Paradigm® Veo™, Medtronic). Participant's usual fast-acting insulin analog and Glucagon (Eli Lilly) will be used. Every 10 minutes, the glucose level as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Newly reconstituted glucagon will be used every 24 hours.
Dual-hormone closed-loop strategy	Continuous glucose monitoring system	Variable subcutaneous insulin and glucagon mini-boluses will be infused using two separate subcutaneous infusion pumps to regulate glucose levels (MiniMed® Paradigm® Veo™, Medtronic). Participant's usual fast-acting insulin analog and Glucagon (Eli Lilly) will be used. Every 10 minutes, the glucose level as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Newly reconstituted glucagon will be used every 24 hours.
Single-hormone closed-loop strategy	Insulin	Variable subcutaneous insulin infusion will be used to regulate glucose levels. Participant's usual fast-acting insulin analog will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump.
Dual-hormone closed-loop strategy	Insulin	Variable subcutaneous insulin and glucagon mini-boluses will be infused using two separate subcutaneous infusion pumps to regulate glucose levels (MiniMed® Paradigm® Veo™, Medtronic). Participant's usual fast-acting insulin analog and Glucagon (Eli Lilly) will be used. Every 10 minutes, the glucose level as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Newly reconstituted glucagon will be used every 24 hours.
Dual-hormone closed-loop strategy	Glucagon	Variable subcutaneous insulin and glucagon mini-boluses will be infused using two separate subcutaneous infusion pumps to regulate glucose levels (MiniMed® Paradigm® Veo™, Medtronic). Participant's usual fast-acting insulin analog and Glucagon (Eli Lilly) will be used. Every 10 minutes, the glucose level as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Newly reconstituted glucagon will be used every 24 hours.

Primary Outcome Measures

Name	Time	Method
Percentage of time of glucose levels below 3.9 mmol/L	15 weeks

Secondary Outcome Measures

Name	Time	Method
HbA1c	15 weeks
Percentage of time of glucose levels spent in the target range	15 weeks	Target range is defined to be between 4 and 10 mmol/L from 7:00 to 22:00 and between 4 and 7.8 mmol/L from 22:00 to 7:00
Area under the curve of glucose levels below 3.9 mmol/L	15 weeks
Percentage of time of closed-loop operation	15 weeks
Percentage of time of glucose sensor availability	15 weeks
Time between failures due to glucose sensor unavailability	15 weeks
Area under the curve of glucose levels below 3.3 mmol/L	15 weeks
Area under the curve of glucose levels below 2.8 mmol/L	15 weeks
Percentage of time of glucose levels below 3.3 mmol/L	15 weeks
Percentage of time of glucose levels below 2.8 mmol/L	15 weeks
Total number of hypoglycemic events below 3.1 mmol/L	15 weeks
Percentage of time of glucose levels above 7.8 mmol/L	15 weeks
Percentage of time of glucose levels above 10.0 mmol/L	15 weeks
Mean glucose levels	15 weeks
Standard deviation of glucose levels	15 weeks
Coefficient of variation of glucose levels	15 weeks
Total daily dose of insulin	24 hours
Total daily dose of glucagon	24 hours
Time between failures due to pump connectivity	15 weeks
Percentage of time when patients switched back to insulin pump therapy	15 weeks
Percentage of time when the closed-loop was automatically switched to insulin pump therapy	15 weeks