SAFE-AP: Automatic Control of Blood Glucose Under Announced and Unannounced Exercise
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of hypoglycaemias
研究概览
简要总结
Achieving near-normoglycemia has been established as the main objective for most patients with diabetes. Despite growing evidence about the health benefits of regular exercise in diabetes, exercise-associated glycemic imbalance remains a challenge in subjects with type 1 diabetes (T1D) due to a higher risk of hypoglycemia.
Automatic glucose control, the so-called artificial pancreas (AP) or closed-loop system, may represent the ideal solution for reaching the therapeutic goals in diabetic patients. Intuitively, closed-loop insulin delivery may be superior to open-loop insulin delivery due to a better compensation of the variability of subcutaneous insulin absorption and the intra-subject insulin sensitivity. However, several challenges exist to effectively realize an optimal closed-loop control of blood glucose during exercise. Indeed, the physical exercise induces one of the major glucose perturbations that need to be controlled by an artificial pancreas and is currently one of the main challenges found in clinical validations of the few existing prototypes of an artificial pancreas. In particular, experiments carried out with the currently used algorithms for glucose control (the so called PID (proportional-integrative-derivative) and MPC) showed that closed-loop insulin delivery is deteriorated by exercise, increasing the risk of hypoglycemia even with pre-exercise carbohydrate ingestion when non-announcement strategies are used.
In this project, a rigorous clinical testing of a novel closed-loop controller ('artificial pancreas') will be carried out in T1D patients treated with continuous subcutaneous insulin infusion (CSII). The innovative element of the controller is a safety auxiliary feedback based on sliding mode reference conditioning (SMRC), which has been demonstrated to limit over-insulinization and the resulting hypoglycemia, reducing glycaemic variability.
Announced and unannounced exercise will be performed in T1D subjects treated with CSII, comparing the number of hypoglycemic episodes with a controller-driven insulin delivery (closed-loop study) based on continuous subcutaneous glucose monitoring (CGM).
If any glucose value <70 mg/dL 15 gr of glucose will be provided. Moreover 15gr of glucose will be provided in AP studies when AP system recommends it.
The hypothesis is that closed loop control will provide better glycemic control, with less hypoglycemia episodes.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18-65 years.
- •Under CSII treatment for at least six months before visit
- •Body mass index between 18 and 30 kg/m
- •HbA1c 6.0-8.5% at visit
- •Physical examination, laboratory data and EKG without alterations. Abnormalities considered clinically irrelevant by the investigator will not be
排除标准
- •Postmenopausal women or women of childbearing age using contraceptives of proven effectiveness and with negative urine pregnancy test at screening visit.
- •Exclusion Criteria:
- •Pregnancy and breastfeeding.
- •Hypoglycemia unawareness (Clarke Test >3).
- •Progressive fatal disease.
- •History of drug or alcohol abuse.
- •History HIV positive, active hepatitis B or hepatitis C.
- •Impaired liver function, as shown in, but not limited to, SGPT (serum gutamate pyruvate transaminase) or SGOT (serum glutamate oxaloacetate transaminase) more than twice the upper limit of normal at Visit
- •Clinically relevant microvascular complications (macroalbuminuria, pre-proliferative and proliferative retinopathy), cardiovascular, hepatic, neurological, endocrine or other systematic, apart from T1D, which may hamper the implementation of the clinical study protocol or interpretation of results study.
- •Scheduled surgery during the study period.
- •Mental conditions that prevent the subject to understand the nature, purpose and possible consequences of the study.
- •Subjects those are unlikely to meet the clinical study protocol, eg uncooperative attitude, inability to return for follow-up visits, or poor probability of completing the study.
- •Using an experimental drug or device during the past 30 days.
研究组 & 干预措施
Open-loop insulin infusion system
Standard Open-loop intensive insulin treatment with continuous subcutaneous insulin infusion (CSII). Commercially available insulin infusion systems will be used.
干预措施: Closed-loop controller with exercise mitigation module (Device)
Closed-loop controller with exercise mitigation module
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with mitigation module.
Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFEAP with mitigation module) based on blood glucose estimations from CGM.
干预措施: Closed-loop controller with exercise mitigation module (Device)
Closed-loop controller with exercise mitigation module
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with mitigation module.
Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFEAP with mitigation module) based on blood glucose estimations from CGM.
干预措施: Closed-loop controller without exercise mitigation module (Device)
Closed-loop controller with exercise mitigation module
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with mitigation module.
Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFEAP with mitigation module) based on blood glucose estimations from CGM.
干预措施: Open-loop insulin infusion system (Device)
Closed-loop controller without exercise mitigation module
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration. Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFEAP without mitigation module) based on blood glucose estimations from CGM.
干预措施: Closed-loop controller with exercise mitigation module (Device)
Closed-loop controller without exercise mitigation module
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration. Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFEAP without mitigation module) based on blood glucose estimations from CGM.
干预措施: Closed-loop controller without exercise mitigation module (Device)
Closed-loop controller without exercise mitigation module
Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration. Automated insulin infusion based on subcutaneous continuous glucose monitoring (CGM). Commercially available insulin infusion systems and CGM devices will be used. However, insulin infusion will be driven by the software under investigation (SAFEAP without mitigation module) based on blood glucose estimations from CGM.
干预措施: Open-loop insulin infusion system (Device)
Open-loop insulin infusion system
Standard Open-loop intensive insulin treatment with continuous subcutaneous insulin infusion (CSII). Commercially available insulin infusion systems will be used.
干预措施: Closed-loop controller without exercise mitigation module (Device)
Open-loop insulin infusion system
Standard Open-loop intensive insulin treatment with continuous subcutaneous insulin infusion (CSII). Commercially available insulin infusion systems will be used.
干预措施: Open-loop insulin infusion system (Device)
结局指标
主要结局
Number of hypoglycaemias
时间窗: 180 minutes psot-exercise period
Number of hypoglycemic episodes (defined as plasma glucose (PG) \<70mg/dL) during exercise and recovery.
次要结局
- AUC (area under curve) of PG during exercise and recovery(180 minutes post-exercise period)
- AUC of SG during exercise and recovery(180 minutes post-exercise period)
- Rate-of-change of glucose during exercise (ROCe) and recovery (ROCr)(180 minutes post-exercise period)
研究者
Ignacio Conget
Head of Endocrinology and Nutrition Department, Principal Investigator
Hospital Clinic of Barcelona