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

Institut de Recherches Cliniques de Montreal

Status and phase: Withdrawn; Phase 2

Conditions: Type 1 Diabetes

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02846857

CLASS-17

Details and patient eligibility

About

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.

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males and females ≥ 12 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 ≤ 11%.

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. Chronic acetaminophen treatment (can interfere with glucose sensor measurements)
7. Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding)
8. Anticholinergic drug (risk of interaction)
9. Pregnancy.
10. Severe hypoglycemic episode within two weeks of screening.
11. Current use of glucocorticoid medication (except low stable dose and inhaled steroids).
12. Known or suspected allergy to the trial products
13. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
14. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
15. Treatments that could interfere with glucagon

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

0 participants in 3 patient groups

Sensor-augmented pump therapy

Active Comparator group

Description:

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.

Treatment:

Device: Continuous glucose monitoring system

Device: Insulin pump

Drug: Insulin

Other: 15-week intervention with sensor-augmented pump

Single-hormone closed-loop strategy

Active Comparator group

Description:

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.

Treatment:

Other: 15-week intervention with single-hormone closed-loop

Device: Continuous glucose monitoring system

Device: Insulin pump

Drug: Insulin

Dual-hormone closed-loop strategy

Active Comparator group

Description:

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.

Treatment:

Drug: Glucagon

Device: Continuous glucose monitoring system

Device: Insulin pump

Other: 15-week intervention with dual-hormone closed-loop

Drug: Insulin