Improving Postprandial Glycaemia by a New Developed Closed-loop Control System - Closedloop4meals
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      Achieving near-normoglycemia has been established as the main objective for most patients
      with diabetes. However, postprandial glucose control is a challenging issue in everyday
      diabetes care. Indeed, excessive postprandial glucose excursions are the major contributors
      to plasma glucose (PG) variability in subjects with type 1 diabetes (T1DM). In addition, the
      poor reproducibility of postprandial glucose response is burdensome for patients and
      healthcare professionals.

      Automatic glucose control, the so-called artificial pancreas 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 postprandial closed-loop control of blood glucose. Indeed, the eating process
      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 and MPC) showed that
      closed-loop insulin delivery often tend to overcorrect hyperglycemia thus increasing the risk
      hypoglycemia.

      In this project, a rigorous clinical testing of a novel closed-loop controller ('artificial
      pancreas') will be carried out in T1DM 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 (in
      simulation studies) to limit over-insulinization and the resulting hypoglycemia, reducing
      glycaemic variability.

      Standardized meal test studies will be performed in T1DM subjects treated with CSII,
      comparing the administration of a classical bolus (open-loop study) with a controller-driven
      prandial insulin delivery (closed-loop study) based on continuous subcutaneous glucose
      monitoring (CGM).

      The hypothesis is that closed loop control will provide better postprandial control,
      especially in terms of reduction of glucose variability and incidence of hypoglycemia.
    


Intervention name(s): Closed-loop insulin infusion system; Open-loop insulin infusion system
Intervention type(s): Device; Other
Intervention description(s): Each subject will undergo two "Open-loop" and two "Closed-loop" meal tests, each one at 1-2 week intervals, thus completing the 4 experiments in about 6 weeks. The day of the experiment, a standard mixed meal test containing 60 g of carbohydrates (CHO), will be administered. On two occasions, patients will receive in a randomized order the standard insulin bolus based on the individual insulin to CHO ratio (First arm, Open-loop study). On the other two occasions they will receive a Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study). Commercial insulin infusion systems and continuous glucose monitoring devices will be used.; Standard subcutaneous insulin infusion based on the individual insulin to carbohydrate ratio. Commercial insulin infusion systems and continuous glucose monitoring devices will be used.
Other intervention name(s): CL4M Controls
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Closed-loop insulin infusion; Postprandial glucose control; Glucose variability