Dual-hormone Closed-loop Glucose Control in Type 1 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Percentage of time with glucose values < 3.9 mmol/l as measured by glucose sensor
研究概览
简要总结
Despite recent pharmacological and technological advantages, hypoglycemia remains to be the key limiting factor in achieving optimal glycemic control in people with type 1 diabetes. State-of-the-art treatment for type 1 diabetes is insulin in pens or pumps that focus on reducing hyperglycemia after relative insulin deficiency e.g. after food intake. In recent years, we focused on adding low-dose glucagon to insulin therapies for the treatment and prevention of hypoglycemia - referred to as "dual-hormone treatment". We have shown that low-dose glucagon is efficient in treating mild hypoglycemia and that several factors may affect its glucose response. Our next step is to test whether the combined delivery of insulin and glucagon can improve glucose control in individuals with type 1 diabetes. In this proposal, we want to test the efficacy, safety and feasibility of a dual-hormone closed-loop system, also known as an artificial pancreas. The closed-loop system involves automatic infusion of glucagon and insulin based on continuous glucose measurements. The system will be tested in a 33-hour in-clinic study comparing the glucose control by the combined automatic delivery of insulin and glucagon with the automatic delivery of insulin-only. The study is performed at Steno Diabetes Center Copenhagen (SDCC) in collaboration with the Technical University of Denmark (DTU). We expect that the study will clarify whether low-dose glucagon added to insulin therapy can improve the glucose control in adults with type 1 diabetes. We believe that the utilization of glucagon will allow for a weight neutral optimization of glucose control, reduce risk of hypoglycemia and reduce disease burden that will reduce diabetes complications and cardiovascular diseases.
详细描述
Rationale: We hypothesize that our newly developed dual-hormone insulin-glucagon closed-loop system (DCL) is safe, efficient and superior to our single-hormone insulin-only closed-loop system (SCL). The study aims to compare the glucose control achieved by DCL with our SCL.
Design: A randomized single-blinded placebo-controlled cross-over 33-hour in-clinic study of glucose control achieved with DCL versus SCL in adults and adolescents with type 1 diabetes.
Participants: 13 insulin-pump treated T1D participants will be included, if they are 15-80 years old, have T1D for ≥ 3 years, use insulin pumps with FiAsp®, and have an HbA1c≤ 8.5% (69 mmol/mol).
Procedures: In this two-phase study 1) we test the operability of our closed-loop systems and 2) compare glucose control by DCL with SCL. The two studies are identical except for the blinding procedures. In the first phase (pilot study), four participants are included, and the glucagon/saline pump is not masked. In the second phase (main study), 13 participants are included, and are as well as the investigators blinded for the content in the glucagon/saline pump.
Two days prior to study visit, a CGM (Dexcom® G6) is place on the participant's abdomen. At study visits, participants arrive in the evening at our research unit and get their insulin pump disconnected. Two study pumps (Dana Diabecare RS®, SOOIL) are attached: one pump infuses insulin (FiAsp®, Novo Nordisk) and the other infuses either glucagon (GlucaGen®, Novo Nordisk) or saline. Once a sampling cannula is placed in an antecubital vein, the study is initiated and the closed-loop system (DCL vs SCL) takes over the glucose control for the next 33 hours. Except from the control algorithm (SCL vs DCL), the study days are identical. Participants can move around freely in the clinic for 33 hours but will perform a 45-min moderate (50% VO2max) exercise session, consume three meals with variant carbohydrate content, and sleep during two overnight periods. Participants will be monitored frequently with blood samples (drawn from the antecubital vein), blood pressure, pulse, and VAS scale for nausea.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dual-hormone
FiAsp(R) - GlucaGen(R)
干预措施: Closed-loop system (Device)
Single-hormone
FiAsp (R) - Saline
干预措施: Closed-loop system (Device)
Dual-hormone
FiAsp(R) - GlucaGen(R)
干预措施: Glucagon (Drug)
结局指标
主要结局
Percentage of time with glucose values < 3.9 mmol/l as measured by glucose sensor
时间窗: 33 hours
Number of carbohydrate interventions to treat hypoglycemia
时间窗: 33 hours
Carbohydrate interventions are predefined and provided in case of hypoglycemia
次要结局
- Percentage of participants achieving (A) time in range (3.9-10 mmol/l) > 70 %, (B) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (C) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by glucose sensor and venous plasma glucose(33 hours)
- Number of hypoglycemic episodes (<3.9 mmol/l and <3.0 mmol/l) overnight and during daytime(33 hours)
- Nadir blood glucose value for each hypoglycemic episode as measured by glucose sensor and venous plasma glucose(33 hours)
- Percentage of time with glucose values < 3.9 mmol/l as measured by venous plasma glucose(33 hours)
- Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by glucose sensor and venous plasma glucose(33 hours)
- Low Blood Glucose Index (LBGI) overnight and during daytime by glucose sensor and venous plasma glucose(33 hours)
- Percentage of participants with a mean blood glucose value (glucose sensor and venous plasma glucose) ≤ 8.6 mmol/l (corresponding to an estimated HbA1c of 7.0% / 53 mmol/mol)(33 hours)
- Mean pulse rate over the study period (beats per min)(33 hours)
- Total time of insulin suspension per study day (UI)(33 hours)
- Mean plasma glucagon(33 hours)
- Total energy expenditure during the study visit (kcal/kg) measured by ActiGraph GT9X Link(33 hours)
- Steps taken during the study visit measured by ActiGraph GT9X Link(33 hours)
- Total sleep time measured by ActiGraph GT9X Link(14 hours)
- Mean blood glucose value measured by glucose sensor and venous plasma glucose(33 hours)
- Percentages of values between glucose sensor and venous plasma glucose in zone A, B, C, D and E in the Clarke Error Grid analysis.(33 hours)
- Difference in participant estimated blood glucose level and plasma glucose level at predefined timepoints(33 hours)
- Percentage of time with glucose values in the range 3.9-8.0 mmol/l measured by glucose sensor and venous plasma glucose(33 hours)
- Percentage of time with glucose values in the range > 13.9 measured by glucose sensor and venous plasma glucose(33 hours)
- Percentage of time with glucose values < 3.0 mmol/l as measured by glucose sensor and venous plasma glucose(33 hours)
- Mean Absolute Relative Difference (MARD) between glucose sensor and venous plasma glucose(33 hours)
- Minutes between lights off and the first sleep episode (Sleep latency) measured by ActiGraph GT9X Link(14 hours)
- Glucose sensor glycemic variability measured as SD and CV during overnight and during daytime(33 hours)
- Percentage of patients with a mean blood glucose value (glucose sensor and venous plasma glucose) ≤ their standard therapy mean glucose value (calculated based on HbA1c measurement)(33 hours)
- Mean blood pressure over the study period (mmHG)(33 hours)
- Total glucagon dose per study day (microgram)(33 hours)
- Difference in participant estimated grams of carbohydrate and actual carbohydrate in study meals(33 hours)
- Minutes per study day (min/d) spent in different levels of activity (sedentary, light, moderate, vigorous, or MVPA) measured by ActiGraph GT9X Link(45 min)
- Mean nausea level measured with a visual analog scale (VAS range: 0-10)(33 hours)
- Total insulin dose per study day (UI)(33 hours)
- Mean plasma insulin aspart(33 hours)
- The percentage of time asleep from lights off to lights on (sleep efficiency) measured by ActiGraph GT9X Link(14 hours)
- Mean Borg scale level during exercise (RANGE:0-10)(45 min)