Type 1 Diabetes Mellitus Prone to Hypoglycemia
Conditions
Keywords
Type 1 Diabetes, Hypoglycemia, Artificial Pancreas, Closed-loop, Automated insulin delivery
Brief summary
Achieving near-normoglycemia has been established as the main objective for most patients with Type 1 Diabetes (T1D). Automated insulin delivery (AID) systems, the so-called artificial pancreas (AP) or closed-loop systems, may represent the ideal solution, especially for patients not reaching the therapeutic goals with multiples doses of insulin or open-loop delivery systems. Despite the advances in recent years that have proven the efficacy and safety of these devices in clinical trials and clinical practice settings, such evidence cannot be extrapolated to highly unstable patients, as problematic hypoglycemia remains an exclusion criterion in most of the trials. The SAFE-AP system is a single-hormone hybrid closed-loop controller based on a proportional derivative with an insulin feedback controller that integrates a safety layer with insulin-on-board constraints and sliding mode reference conditioning. The hybrid closed-loop system includes a second safety feedback loop with a controller that triggers carbohydrate recommendations to the patient. Both control loops are coordinated to ensure that the counter-regulatory effect of rescue carbohydrates is not counteracted with insulin. Such system has been previously proven effective in unannounced exercise, one of the main challenges in AID systems development. Additionally, the algorithm has been recently tailored to achieve a better control in the subgroup of T1D patients prone to hypoglycemia. In this project, a rigorous clinical testing of the SAFE-AP system will be carried out in 12 patients with T1D and problematic hypoglycemia, despite treatment with continuous subcutaneous insulin infusion. The safety and performance of the system will be evaluated in a 32-hour pilot study, including 4 meals, one overnight period and 2 unannounced aerobic exercise sessions. The study will be performed in a hospital setting with the on-site supervision of a specialized nurse and a diabetologist, as well as an engineer in remote control.
Interventions
DEVICEAutomated Insulin Delivery System (SAFE-AP)
Each subject will undergo a 32-hour in-hospital study, including 4 meals (60 grams of carbohydrates each, except 50 grams for breakfast), one overnight period and 2 unannounced aerobic exercise sessions. Each exercise session consists of three 15-minute sets on a cycle ergometer at 70% of maximum heart rate with 5 minutes of rest between sets.
Sponsors
Universitat Politècnica de València
Universitat de Girona
Hospital Clinic of Barcelona
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects aged 18 or more with Type 1 Diabetes for at least 5 years. * Treated with continuous subcutaneous insulin infusion (CSII) for at least six months. * Trained to carbohydrate counting. * Subjects prone to hypoglycemia, despite optimal diabetes management and hypoglycemia-specific education programs, as defined by \>4 hypoglycemic episodes per week and at least one of the following: 1. Occurrence of at least 2 severe hypoglycemic episodes during the last 2 years (need for third party). 2. Occurrence of at least 1 severe hypoglycemic episode during the last 2 years and high glycemic variability (coefficient of variation \>36%). 3. Impaired awareness of hypoglycemia (Clarke test ≥4). * Physical examination, laboratory data and EKG without alterations. Abnormalities considered clinically irrelevant by the investigator will not be
Exclusion criteria
. * Negative SARS-CoV-2 PCR test performed at arrival. * Subject willing to wear the SAFE-AP system continuously throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of CGM time in glucose range 70-180 mg/dl during the study. | From 12 AM of the first day of study until 4 PM of the second day of study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of CGM time in glucose range 70-180 mg/dl during exercise and recovery | Defined as 3 hours after exercise initiation | — |
| Percentage of CGM time in glucose range 70-180 mg/dl during postprandial period | Defined as 4 hours since mealtime | — |
| Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during the study | From 22 PM of the first day of study until 7 AM of the second day of study | — |
| Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during nighttime | From 22 PM of the first day of study until 7 AM of the second day of study | — |
| Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during exercise and recovery | Defined as 3 hours after exercise initiation | — |
| Percentage of CGM time in hypoglycemia (<70 mg/dL and <54 mg/dL) during postprandial period | Defined as 4 hours since mealtime | — |
| Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during the study | From 22 PM of the first day of study until 7 AM of the second day of study | — |
| Percentage of CGM time in glucose range 70-180 mg/dl during nighttime | From 22 PM of the first day of study until 7 AM of the second day of study | — |
| Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during exercise and recovery | Defined as 3 hours after exercise initiation | — |
| Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during postprandial period | Defined as 4 hours since mealtime | — |
| Glucose coefficient of variation during the study | From 22 PM of the first day of study until 7 AM of the second day of study | — |
| Number of hypoglycemic events | From 22 PM of the first day of study until 7 AM of the second day of study | Defined as sensor glucose \<70 mg/dL during 15 minutes or symptomatic hypoglycemia confirmed with plasma glucose |
| Number of carbohydrate rescue events during the study | From 22 PM of the first day of study until 7 AM of the second day of study | — |
| Number of acute metabolic events during the study | From 22 PM of the first day of study until 7 AM of the second day of study | Defined as severe hypoglycemia and diabetic ketoacidosis |
| Percentage of CGM time in hyperglycemia (>180 mg/dL and >250 mg/dL) during nighttime | From 22 PM of the first day of study until 7 AM of the second day of study | — |
Countries
Spain
Outcome results
None listed