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

November 14, 2015 updated by: Fundación para la Investigación del Hospital Clínico de Valencia

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clínic i Universitari de Barcelona
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • CL4M Controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Eight-hour post-prandial period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
the 3-8 hour post-prandial interval

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
0-8h post-prandial period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

Collaborators

Hospital Clinic of Barcelona
Universitat de Girona
Universitat Politècnica de València

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

March 27, 2014

First Submitted That Met QC Criteria

March 31, 2014

First Posted (Estimate)

April 1, 2014

Study Record Updates

Last Update Posted (Estimate)

November 17, 2015

Last Update Submitted That Met QC Criteria

November 14, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL4M Controls
  • 470/13/EC (Registry Identifier: Spain Agency of Medicines - AEMPS)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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