Type 1 Diabetes
Conditions
Keywords
Closed-loop system, Artificial pancreas, Type 1 diabetes, Hypoglycemia, Insulin, Glucagon
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.
Interventions
OTHER15-week intervention with sensor-augmented pump
A sensor will be inserted on the day before the start of the intervention by the participant. The participant will also have to install the study insulin pump. Participants will be advised to continue with study intervention at home for the next 15 weeks. Participants will have been previously shown how to use the study insulin pump.
OTHER15-week intervention with single-hormone closed-loop
A sensor will be inserted on the day before the start of the intervention by the participant. On the first day of the intervention, participants will be admitted to the clinical research facility anytime between 8:00 am and 11:30 am. Training on connection and disconnection of the system, meal boluses, etc. will be given. Only participants demonstrating competency on use of study devices will be allowed to continue to the home study phase. Participants will be advised to continue with study intervention at home for the next 15 weeks.
OTHER15-week intervention with dual-hormone closed-loop
A sensor will be inserted on the day before the start of the intervention by the participant. On the first day of the intervention, participants will be admitted to the clinical research facility anytime between 8:00 am and 11:30 am. Training on connection and disconnection of the system, meal boluses, etc. will be given. Only participants demonstrating competency on use of study devices will be allowed to continue to the home study phase. Participants will be advised to continue with study intervention at home for the next 15 weeks. Participants will have to reconstitute glucagon everyday.
DEVICEInsulin pump
MiniMed® Paradigm® Veo™, Medtronic
DEVICEContinuous glucose monitoring system
Enlite sensor®, Medtronic
DRUGInsulin
Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)
DRUGGlucagon
Glucagon (Eli Lilly) will be used during dual-hormone closed-loop strategy.
Sponsors
Institut de Recherches Cliniques de Montreal
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of time of glucose levels below 3.9 mmol/L | 15 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coefficient of variation of glucose levels | 15 weeks | — |
| Total daily dose of insulin | 24 hours | — |
| Total daily dose of glucagon | 24 hours | — |
| 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 | — |
| 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 | — |
| Percentage of time of closed-loop operation | 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 | — |
| Percentage of time of glucose sensor availability | 15 weeks | — |
| Time between failures due to glucose sensor unavailability | 15 weeks | — |
| 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 | — |
| Total number of hypoglycemic events below 3.1 mmol/L | 15 weeks | — |
Outcome results
None listed