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
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Percentage of time of glucose levels below 3.9 mmol/L
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%.
排除标准
- •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)
- •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
研究组 & 干预措施
Sensor-augmented pump therapy
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.
干预措施: 15-week intervention with sensor-augmented pump (Other)
Sensor-augmented pump therapy
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.
干预措施: Insulin pump (Device)
Sensor-augmented pump therapy
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.
干预措施: Continuous glucose monitoring system (Device)
Sensor-augmented pump therapy
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.
干预措施: Insulin (Drug)
Single-hormone closed-loop strategy
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.
干预措施: 15-week intervention with single-hormone closed-loop (Other)
Single-hormone closed-loop strategy
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.
干预措施: Insulin pump (Device)
Single-hormone closed-loop strategy
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.
干预措施: Continuous glucose monitoring system (Device)
Single-hormone closed-loop strategy
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.
干预措施: Insulin (Drug)
Dual-hormone closed-loop strategy
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.
干预措施: 15-week intervention with dual-hormone closed-loop (Other)
Dual-hormone closed-loop strategy
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.
干预措施: Insulin pump (Device)
Dual-hormone closed-loop strategy
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.
干预措施: Continuous glucose monitoring system (Device)
Dual-hormone closed-loop strategy
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.
干预措施: Insulin (Drug)
Dual-hormone closed-loop strategy
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.
干预措施: Glucagon (Drug)
结局指标
主要结局
Percentage of time of glucose levels below 3.9 mmol/L
时间窗: 15 weeks
次要结局
- HbA1c(15 weeks)
- Percentage of time of glucose levels spent in the target range(15 weeks)
- 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)
研究者
Rémi Rabasa-Lhoret
Professor of Medicine
Institut de Recherches Cliniques de Montreal