Clinical trial NCT02846857: Closed-loop Control of Glucose Levels (Artificial Pancreas) for 15 Weeks in Adolescents and Adults With Type 1 Diabetes
Official title: An Open-label, Randomized, Multicenter 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 15 Weeks in Free-living Outpatient Conditions in Adolescents and Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Closed-loop system
Artificial pancreas
Type 1 diabetes
Hypoglycemia
Insulin
Glucagon
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
First posted: 2016-07-27
Enrollment: 0
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: 15 weeks
Secondary outcomes:
measure: HbA1c
timeFrame: 15 weeks
measure: Percentage of time of glucose levels spent in the target range
timeFrame: 15 weeks
measure: Area under the curve of glucose levels below 3.9 mmol/L
timeFrame: 15 weeks
measure: Area under the curve of glucose levels below 3.3 mmol/L
timeFrame: 15 weeks
measure: Area under the curve of glucose levels below 2.8 mmol/L
timeFrame: 15 weeks
measure: Percentage of time of glucose levels below 3.3 mmol/L
timeFrame: 15 weeks
measure: Percentage of time of glucose levels below 2.8 mmol/L
timeFrame: 15 weeks
measure: Total number of hypoglycemic events below 3.1 mmol/L
timeFrame: 15 weeks
measure: Percentage of time of glucose levels above 7.8 mmol/L
timeFrame: 15 weeks
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: 15 weeks
measure: Mean glucose levels
timeFrame: 15 weeks
measure: Standard deviation of glucose levels
timeFrame: 15 weeks
measure: Coefficient of variation of glucose levels
timeFrame: 15 weeks
measure: Total daily dose of insulin
timeFrame: 24 hours
measure: Total daily dose of glucagon
timeFrame: 24 hours
measure: Percentage of time of closed-loop operation
timeFrame: 15 weeks
measure: Percentage of time of glucose sensor availability
timeFrame: 15 weeks
measure: Time between failures due to glucose sensor unavailability
timeFrame: 15 weeks
measure: Time between failures due to pump connectivity
timeFrame: 15 weeks
measure: Percentage of time when patients switched back to insulin pump therapy
timeFrame: 15 weeks
measure: Percentage of time when the closed-loop was automatically switched to insulin pump therapy
timeFrame: 15 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References: