Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1, Insulin, Exercise, Closed-loop, Artificial Pancreas
Brief 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.
Interventions
DEVICEClosed-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.
DEVICEClosed-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.
Standard subcutaneous insulin infusion based on the individual insulin sensibility. Commercial insulin infusion systems and continuous subcutaneous glucose monitoring devices will be used.
Sponsors
Universitat Politècnica de València
Universitat de Girona
Hospital Clinic of Barcelona
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Longitudinal, prospective, interventional study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18-65 years. * Under CSII treatment for at least six months before visit 1. * Body mass index between 18 and 30 kg/m2. * HbA1c 6.0-8.5% at visit 1. * Physical examination, laboratory data and EKG without alterations. Abnormalities considered clinically irrelevant by the investigator will not be
Exclusion criteria
. * Postmenopausal women or women of childbearing age using contraceptives of proven effectiveness and with negative urine pregnancy test at screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of hypoglycaemias | 180 minutes psot-exercise period | Number of hypoglycemic episodes (defined as plasma glucose (PG) \<70mg/dL) during exercise and recovery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC (area under curve) of PG during exercise and recovery | 180 minutes post-exercise period | AUC0\_180min, AUC0\_60min and AUC60\_180min of PG and time spent in different glycemic ranges (\< 70; 70-180; \> 180 mg/dL) during exercise and recovery. |
| AUC of SG during exercise and recovery | 180 minutes post-exercise period | AUC0-180min, AUC0-60min and AUC60-180min of sensor glucose (SG) and time spent in different glycemic ranges (\< 70; 70-180; \> 180 mg/dL) during exercise and recovery. |
| Rate-of-change of glucose during exercise (ROCe) and recovery (ROCr) | 180 minutes post-exercise period | — |
Countries
Spain
Outcome results
None listed