SAFE-AP: Automatic Control of Blood Glucose Under Announced and Unannounced Exercise (SAFE-AP3)

Hospital Clinic of Barcelona

Status: Completed

Conditions: Diabetes Mellitus, Type 1

Treatments: Device: Closed-loop controller without exercise mitigation module; Device: Closed-loop controller with exercise mitigation module; Device: Open-loop insulin infusion system

Study type: Interventional

Funder types: Other

Identifiers

NCT03577158

SAFE-AP3

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Exclusion criteria

• Pregnancy and breastfeeding.
• Hypoglycemia unawareness (Clarke Test >3).
• Progressive fatal disease.
• History of drug or alcohol abuse.
• History HIV positive, active hepatitis B or hepatitis C.
• Impaired liver function, as shown in, but not limited to, SGPT (serum gutamate pyruvate transaminase) or SGOT (serum glutamate oxaloacetate transaminase) more than twice the upper limit of normal at Visit 1.
• Clinically relevant microvascular complications (macroalbuminuria, pre-proliferative and proliferative retinopathy), cardiovascular, hepatic, neurological, endocrine or other systematic, apart from T1D, which may hamper the implementation of the clinical study protocol or interpretation of results study.
• Scheduled surgery during the study period.
• Mental conditions that prevent the subject to understand the nature, purpose and possible consequences of the study.
• Subjects those are unlikely to meet the clinical study protocol, eg uncooperative attitude, inability to return for follow-up visits, or poor probability of completing the study.
• Using an experimental drug or device during the past 30 days.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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10 participants in 3 patient groups

Closed-loop controller with exercise mitigation module

Experimental group

Description:

Sliding Mode Reference Conditioning (SMRC) Closed-loop insulin administration with mitigation module. 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 software under investigation (SAFEAP with mitigation module) based on blood glucose estimations from CGM.

Treatment:

Device: Closed-loop controller with exercise mitigation module

Device: Open-loop insulin infusion system

Device: Closed-loop controller without exercise mitigation module

Closed-loop controller without exercise mitigation module

Experimental group

Description:

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 software under investigation (SAFEAP without mitigation module) based on blood glucose estimations from CGM.

Treatment:

Device: Closed-loop controller with exercise mitigation module

Device: Open-loop insulin infusion system

Device: Closed-loop controller without exercise mitigation module

Open-loop insulin infusion system

Active Comparator group

Description:

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

Treatment:

Device: Closed-loop controller with exercise mitigation module

Device: Open-loop insulin infusion system

Device: Closed-loop controller without exercise mitigation module