Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format

Study Overview
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Brief Summary
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In previous studies, we tested the feasibility of a bi-hormonal closed loop system. This system for automated control of blood glucose in patients with type 1 diabetes was tested in the clinical research center as well as at the home of the patients. Glucose control with automated closed loop control was comparable to patient-managed open loop control. The closed loop system has been further developed and miniaturized (from backpack to smartphone size) in order to interfere as little as possible with daily patient life. The aim of this trial is to assess the efficacy of the new prototype at the home of the patient. It is hypothesized that the closed loop system provides better glucose control than standard open loop therapy.

Official Title
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Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format, APPEL 4

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Device: Artificial Pancreas (Inreda Diabetic BV)
* Device: Insulin pump therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with diabetes mellitus type 1 Treated with insulin pump therapy for a minimum of 6 months Age between 18 and 75 years Willing and able to sign informed consent Exclusion Criteria: Impaired awareness of hypoglycemia (score ≥ 4) according to Gold and/or Clarke questionnaire BMI > 35 kg/m2 HbA1c > 97 mmol/mol (=11.0 %) Use of heparin, coumarin derivatives or oral corticosteroids Skin condition prohibiting needle insertion Pregnancy and/or breastfeeding Living alone during the closed loop period (the patient may ask someone to stay over temporarily) Any condition that the local investigator feels would have interfere with trial participation or the evaluation of the results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Open Loop<br>4 days patient-managed insulin pump therapy with blinded continuous glucose monitoring | Device: Insulin pump therapy<br>* Patients' own insulin pump with fast-acting insulin analog<br>* Other names: Continuous subcutaneous insulin infusion;|
| Experimental: Closed Loop<br>4 days of automated blood glucose control with the Artificial Pancreas (Inreda Diabetic BV) | Device: Artificial Pancreas (Inreda Diabetic BV)<br>* Bi-hormonal reactive closed loop system without mealtime announcement, miniaturized prototype<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean sensor glucose concentration |  | Day 2-4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of time spent in each glycemic category | Glycemic categories: Low glucose (<3.9 mmol/l and ≥ 3.3 mmol/l) Very low glucose (<3.3 mmol/l and ≥ 2.8 mmol/l) Dangerously low glucose (<2.8 mmol/l) High glucose (> 10 mmol/l and ≤ 13.9 mmol/l) Very high glucose (> 13.9 mmol/l and ≤ 22.2 mmol/) Dangerously high glucose (> 22.2 mmol/l) | Day 2-4 | 
| Number of events in each glycemic category | Glycemic categories: Low glucose (<3.9 mmol/l and ≥ 3.3 mmol/l) Very low glucose (<3.3 mmol/l and ≥ 2.8 mmol/l) Dangerously low glucose (<2.8 mmol/l) High glucose (> 10 mmol/l and ≤ 13.9 mmol/l) Very high glucose (> 13.9 mmol/l and ≤ 22.2 mmol/) Dangerously high glucose (> 22.2 mmol/l) | Day 2-4 | 
| Number of carbohydrate-treated hypoglycemic events |  | Day 2-4 | 
| Proportion of time spent in euglycemia (≥ 3.9 mmol/l and ≤ 10 mmol/l) |  | Day 2-4 | 
| Glycemic variability | Calculated as Interquartile Range (IQR) | Day 2-4 | 
| Mean sensor glucose concentration during specific periods | Periods: Day Night Postprandial | Day 2-4 | 
| Mean absolute relative difference between sensor values and self-monitored blood glucose values |  | Day 2-4 | 
| Heart rate |  | Day 2-4 | 
| Physical activity | Acceleration measured with a tri-axial accelerometer. The physical activity parameter is calculated as the magnitude of the total acceleration vector (square root of the sum of the squared axes). | Day 2-4 | 
| Mean glucose concentration per day | Intervention arm (closed loop) only | Day 1-4 | 
| Time that the control algorithm is inactive | Intervention arm (closed loop) only | Day 1-4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial pancreas, Bi-hormonal closed loop, Diabetes Type 1