Clinical trial NCT02100488: Improving Postprandial Glycaemia by a New Developed Closed-loop Control System - Closedloop4meals
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Keywords: Closed-loop insulin infusion
Postprandial glucose control
Glucose variability
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
Collaborators: name: Hospital Clinic of Barcelona
name: Universitat Politècnica de València
name: Universitat de Girona
First posted: 2014-04-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Subjects with type 1 diabetes mellitus
* Continuous subcutaneous insulin infusion (CSII) treatment for at least six months before Visit 1
* Body mass index of between 18 and 30 kg/m2
* HbA1c 6.0-8.5% at Visit 1
* Normal laboratory values, ECG, and vital signs unless the investigator considered an abnormality to be clinically irrelevant
* Women postmenopausal or using contraception judged by the investigator to be adequate (e.g., oral contraceptives, intra-uterine device or surgical treatment), or with a negative negative urine pregnancy tests at visits 1, 3 and 5

Exclusion Criteria:

* Pregnancy and lactation
* History of hypersensitivity to the study medications or to drugs with similar chemical structures
* Hypoglycaemia unawareness
* Progressive fatal diseases
* History of drug or alcohol abuse
* History of positive HIV or hepatitis B or C test
* Impaired hepatic function, as shown by, but not limited to, SGPT or SGOT of more than twice the upper limit of the normal range at visit 1
* Impaired renal function, as shown by, but not limited to, serum creatinine \> 1.5 mg/dL at visit 1
* Clinically relevant microvascular (pre-proliferative and proliferative retinopathy and macroalbuminuria), cardiovascular, hepatic, neurologic, endocrine or other major systemic diseases other than T1DM which could hinder implementation of the clinical study protocol or interpretation of the study results
* Pre-planned surgery during the study
* Blood donation of more than 500 ml during the past three months for men, or during the past six months for women
* Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
* Subject unlikely to comply with clinical study protocol, e.g., uncooperative attitude, inability to return for follow-up visits, or poor likelihood of completing the study
* Receipt of an experimental drug or use of an experimental device during the past 30 days.

Primary outcomes:
measure: Intra-subject postprandial glycemic variability
timeFrame: Eight-hour post-prandial period
Secondary outcomes:
measure: CV_AUC-PG_3-8h
timeFrame: the 3-8 hour post-prandial interval
Other outcomes:
measure: AUC_PG_0-8h
timeFrame: the 8h post-prandial period
measure: Time into range
timeFrame: 0-8h post-prandial period
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic i Universitari de Barcelona
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Department of Medicine, Division of Endocrinology and Nutrition, Clinic University Hospital of Valencia - Fundación INCLIVA, University of Valencia, Valencia, Spain.
name: Francisco Javier Ampudia-Blasco, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unidad de Diabetes. Servicio de Endocrinología y Nutrición, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
name: Ignacio Conget, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Institute of Control Systems and Industrial Computing (ai2 Institute), Polytechnic University of Valencia, Valencia, Spain
name: Jorge Bondia, PhD
role: STUDY_DIRECTOR
affiliation: Institute of Informatics and Applications, University of Girona, Girona, Spain
name: Josep Vehí, PhD
role: STUDY_DIRECTOR
References:
citation: Revert A, Garelli F, Pico J, De Battista H, Rossetti P, Vehi J, Bondia J. Safety auxiliary feedback element for the artificial pancreas in type 1 diabetes. IEEE Trans Biomed Eng. 2013 Aug;60(8):2113-22. doi: 10.1109/TBME.2013.2247602. Epub 2013 Feb 15.
citation: Rossetti P, Quiros C, Moscardo V, Comas A, Gimenez M, Ampudia-Blasco FJ, Leon F, Montaser E, Conget I, Bondia J, Vehi J. Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target. Diabetes Technol Ther. 2017 Jun;19(6):355-362. doi: 10.1089/dia.2016.0443. Epub 2017 May 1.