Improving Postprandial Glycaemia by a New Developed Closed-loop Control System - Closedloop4meals

NCT ID: NCT02100488

Last Updated: 2015-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2015-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Open-loop insulin infusion system

Standard Open-loop intensive insulin treatment with continuous insulin infusion (CSII). Commercially available insulin infusion systems will be used.

Group Type ACTIVE_COMPARATOR

Open-loop insulin infusion system

Intervention Type OTHER

Standard subcutaneous insulin infusion based on the individual insulin to carbohydrate ratio. Commercial insulin infusion systems and continuous glucose monitoring devices will be used.

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.

Group Type EXPERIMENTAL

Closed-loop insulin infusion system

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

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.

Intervention Type OTHER

Other Intervention Names

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CL4M Controls

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Clinic of Barcelona

OTHER

Sponsor Role collaborator

Universitat Politècnica de València

OTHER

Sponsor Role collaborator

Universitat de Girona

OTHER

Sponsor Role collaborator

Fundación para la Investigación del Hospital Clínico de Valencia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Francisco Javier Ampudia-Blasco, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Medicine, Division of Endocrinology and Nutrition, Clinic University Hospital of Valencia - Fundación INCLIVA, University of Valencia, Valencia, Spain.

Ignacio Conget, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Unidad de Diabetes. Servicio de Endocrinología y Nutrición, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain

Jorge Bondia, PhD

Role: STUDY_DIRECTOR

University Institute of Control Systems and Industrial Computing (ai2 Institute), Polytechnic University of Valencia, Valencia, Spain

Josep Vehí, PhD

Role: STUDY_DIRECTOR

Institute of Informatics and Applications, University of Girona, Girona, Spain

Locations

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Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Site Status

Hospital Clínic i Universitari de Barcelona

Barcelona, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 23428611 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28459603 (View on PubMed)

Other Identifiers

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470/13/EC

Identifier Type: REGISTRY

Identifier Source: secondary_id

CL4M Controls

Identifier Type: -

Identifier Source: org_study_id