SAFE-AP: Automatic Control of Blood Glucose Under Announced and Unannounced Exercise

Summary

Achieving near-normoglycemia has been established as the main objective for most patients with diabetes. Despite growing evidence about the health benefits of regular exercise in diabetes, exercise-associated glycemic imbalance remains a challenge in subjects with type 1 diabetes (T1D) due to a higher risk of hypoglycemia.

Automatic glucose control, the so-called artificial pancreas (AP) 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 closed-loop control of blood glucose during exercise. Indeed, the physical exercise 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 (proportional-integrative-derivative) and MPC) showed that closed-loop insulin delivery is deteriorated by exercise, increasing the risk of hypoglycemia even with pre-exercise carbohydrate ingestion when non-announcement strategies are used.

In this project, a rigorous clinical testing of a novel closed-loop controller ('artificial pancreas') will be carried out in T1D 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 to limit over-insulinization and the resulting hypoglycemia, reducing glycaemic variability.

Announced and unannounced exercise will be performed in T1D subjects treated with CSII, comparing the number of hypoglycemic episodes with a controller-driven insulin delivery (closed-loop study) based on continuous subcutaneous glucose monitoring (CGM).

If any glucose value \<70 mg/dL 15 gr of glucose will be provided. Moreover 15gr of glucose will be provided in AP studies when AP system recommends it.

The hypothesis is that closed loop control will provide better glycemic control, with less hypoglycemia episodes.

Conditions

• Diabetes Mellitus, Type 1

Interventions

DEVICE

Closed-loop controller with exercise mitigation module

Each subject will undergo three exercise tests, each one at 1-2 week intervals, thus completing the 3 experiments in about 6 weeks. The day of the experiment, the participant will do 3 sets of 15 minutes of cycloergometer at 70% of VO2max with 5 minutes of rest between them. On the first arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with a mitigation mode, based on subcutaneous continuous glucose monitoring (First arm, Closed-loop study with mitigation module). Commercial insulin infusion systems and continuous glucose monitoring devices will be used.

DEVICE

Closed-loop controller without exercise mitigation module

On the second arm, participants will receive Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration without a mitigation mode, based on subcutaneous continuous glucose monitoring (Second arm, Closed-loop study without mitigation module). Commercial insulin infusion systems and continuous glucose monitoring devices will be used.

DEVICE

Open-loop insulin infusion system

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

Sponsors & Collaborators

• Universitat Politècnica de València

  collaborator OTHER

• Universitat de Girona

  collaborator OTHER

• Hospital Clinic of Barcelona

  lead OTHER

Principal Investigators

• Jorge Bondia, PhD · Universitat Politècnica de València

• Josep Vehi, PhD · Universitat de Girona

• Ignacio Conget Donlo, MD · Hospital Clinic of Barcelona

• Marga Gimenez Alvarez, MD · Hospital Clinic of Barcelona

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-01

Primary Completion

2019-04-30

Completion

2019-07-31

Countries

• Spain

Study Locations