SAFE-AP: Automatic Control of Blood Glucose Under Announced and Unannounced Exercise
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      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.
    


Intervention name(s): Closed-loop controller with exercise mitigation module; Closed-loop controller without exercise mitigation module; Open-loop insulin infusion system
Intervention type(s): Device; Device; Device
Intervention description(s): Each subject will undergo three exercise tests, each one at 1-2 week intervals, thus completing the 3 experiments in about 6 weeks. The day of the experiment, the participant will do 3 sets of 15 minutes of cycloergometer at 70% of VO2max with 5 minutes of rest between them. On the first arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with a mitigation mode, based on subcutaneous continuous glucose monitoring (First arm, Closed-loop study with mitigation module).
Commercial insulin infusion systems and continuous glucose monitoring devices will be used.; On the second arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration without a mitigation mode, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study without mitigation module).
Commercial insulin infusion systems and continuous glucose monitoring devices will be used.; Standard subcutaneous insulin infusion based on the individual insulin sensibility. Commercial insulin infusion systems and continuous subcutaneous glucose monitoring devices will be used.
Intervention MeSH terms: Insulin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Longitudinal, prospective, interventional study.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Diabetes Mellitus, Type 1; Insulin; Exercise; Closed-loop; Artificial Pancreas