Improving Postprandial Glycaemia by a New Developed Closed-loop Control System - Closedloop4meals (CL4M-Controls)
|ClinicalTrials.gov Identifier: NCT02100488|
Recruitment Status : Completed
First Posted : April 1, 2014
Last Update Posted : November 17, 2015
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.
|Condition or disease||Intervention/treatment|
|Diabetes Mellitus, Type 1||Device: Closed-loop insulin infusion system Other: Open-loop insulin infusion system|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||Improving Postprandial Glycaemia by a New Developed Closed-loop Control System (Closedloop4meals). An Interdisciplinary, Investigator's Initiated Project for Optimization of Glucose Control in Type1 Diabetic Subjects|
|Study Start Date :||March 2014|
|Primary Completion Date :||July 2015|
|Study Completion Date :||October 2015|
Active Comparator: Open-loop insulin infusion system
Standard Open-loop intensive insulin treatment with continuous insulin infusion (CSII). Commercially available insulin infusion systems will be used.
Other: Open-loop insulin infusion system
Standard subcutaneous insulin infusion based on the individual insulin to carbohydrate ratio. Commercial insulin infusion systems and continuous glucose monitoring devices will be used.
Experimental: Closed-loop insulin infusion system
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 by the software under investigation (CL4M Controls) based on blood glucose estimations from CGM.
Device: Closed-loop insulin infusion system
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.
Other Name: CL4M Controls
- Intra-subject postprandial glycemic variability [ Time Frame: Eight-hour post-prandial period ]
Clinical validation of a new algorithm (glucose controller) for closed-loop control of postprandial glucose in comparison with a standard bolus (open-loop control), in type 1 diabetic subjects using insulin pump therapy. The robustness and effectiveness of the new algorithm for closed-loop glycaemic control (PID controller modified by SMRC-based external loop adjustments) will be evaluated through measurement of intra-subject postprandial glycemic variability expressed as the coefficient of variation (CV) of the area under the curve (AUC) of plasma glucose (PG) during the 8h post-prandial period (CV_AUC-PG_0-8h).
The hypothesis is that closed-loop insulin infusion reduces postprandial glucose variability as compared with standard treatment.
- CV_AUC-PG_3-8h [ Time Frame: the 3-8 hour post-prandial interval ]Coefficient of variation of the area under the curve (AUC) of plasma glucose (PG) during the late postprandial phase.
- AUC_PG_0-8h [ Time Frame: the 8h post-prandial period ]Area under the curve of plasma glucose (PG) during the 8h post-prandial period
- Time into range [ Time Frame: 0-8h post-prandial period ]Time spent in an acceptable glycaemic range (70-180 mg/dl), during the postprandial period
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02100488
|Hospital Clínic i Universitari de Barcelona|
|Barcelona, Spain, 08036|
|Hospital Clínico Universitario de Valencia|
|Valencia, Spain, 46010|
|Principal Investigator:||Francisco Javier Ampudia-Blasco, MD, PhD||Department of Medicine, Division of Endocrinology and Nutrition, Clinic University Hospital of Valencia - Fundación INCLIVA, University of Valencia, Valencia, Spain.|
|Principal Investigator:||Ignacio Conget, MD, PhD||Unidad de Diabetes. Servicio de Endocrinología y Nutrición, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain|
|Study Director:||Jorge Bondia, PhD||University Institute of Control Systems and Industrial Computing (ai2 Institute), Polytechnic University of Valencia, Valencia, Spain|
|Study Director:||Josep Vehí, PhD||Institute of Informatics and Applications, University of Girona, Girona, Spain|