Improving Postprandial Glycaemia by a New Developed Closed-loop Control System - Closedloop4meals (CL4M-Controls)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor:
Collaborators:
Hospital Clinic of Barcelona
Universidad Politécnica de Valencia
Universidad de Girona
Information provided by (Responsible Party):
Fundación para la Investigación del Hospital Clínico de Valencia
ClinicalTrials.gov Identifier:
NCT02100488
First received: March 27, 2014
Last updated: June 12, 2014
Last verified: March 2014
  Purpose

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 Intervention
Diabetes Mellitus, Type 1
Device: Closed-loop insulin infusion system
Other: Open-loop insulin infusion system

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Fundación para la Investigación del Hospital Clínico de Valencia:

Primary Outcome Measures:
  • Intra-subject postprandial glycemic variability [ Time Frame: Eight-hour post-prandial period ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • CV_AUC-PG_3-8h [ Time Frame: the 3-8 hour post-prandial interval ] [ Designated as safety issue: No ]
    Coefficient of variation of the area under the curve (AUC) of plasma glucose (PG) during the late postprandial phase.


Other Outcome Measures:
  • AUC_PG_0-8h [ Time Frame: the 8h post-prandial period ] [ Designated as safety issue: No ]
    Area under the curve of plasma glucose (PG) during the 8h post-prandial period

  • Time into range [ Time Frame: 0-8h post-prandial period ] [ Designated as safety issue: No ]
    Time spent in an acceptable glycaemic range (70-180 mg/dl), during the postprandial period


Estimated Enrollment: 20
Study Start Date: March 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02100488

Contacts
Contact: Lola Iglesias, RPh 0034 96 3862894 diglesias@incliva.es
Contact: Paolo Rossetti, MD, PhD prossetti73@gmail.com

Locations
Spain
Hospital Clínic i Universitari de Barcelona Not yet recruiting
Barcelona, Spain, 08036
Contact: Ignacio Conget, MD, PhD    0034 93 2279846    iconget@clinic.ub.es   
Contact: Marga Gímenez, MD, PhD       GIMENEZ@clinic.ub.es   
Principal Investigator: Ignacio Conget, MD, PhD         
Sub-Investigator: Marga Gímenez, MD, PhD         
Sub-Investigator: Carmen Quirós, MD         
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Francisco Javier Ampudia-Blasco, MD, PhD       ampudia_fra@gva.es   
Contact: Paolo Rossetti, MD, PhD       prossetti73@gmail.com   
Sub-Investigator: Paolo Rossetti, MD, PhD         
Principal Investigator: Francisco Javier Ampudia-Blasco, MD, PhD         
Sponsors and Collaborators
Fundación para la Investigación del Hospital Clínico de Valencia
Hospital Clinic of Barcelona
Universidad Politécnica de Valencia
Universidad de Girona
Investigators
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
  More Information

Additional Information:
Publications:
Responsible Party: Fundación para la Investigación del Hospital Clínico de Valencia
ClinicalTrials.gov Identifier: NCT02100488     History of Changes
Other Study ID Numbers: CL4M Controls, 470/13/EC
Study First Received: March 27, 2014
Last Updated: June 12, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundación para la Investigación del Hospital Clínico de Valencia:
Closed-loop insulin infusion
Postprandial glucose control
Glucose variability

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014