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, the investigators tested the feasibility of a bi-hormonal reactive closed loop system without mealtime announcement. This system for automated control of blood glucose in patients with type 1 diabetes was tested in the clinical research center (APPEL 1 and 2) as well as at the home of the patients (APPEL 3 and 4). After the APPEL 4 study some improvements have been made to the miniaturized prototype to allow patients to operate the system independently and additional risk control measures were included. The main objective of this study is to assess the efficacy of this improved closed loop system.

Official Title
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Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format, APPEL 5

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Device: Insulin pump therapy (with or without glucose sensor)
* Device: Artificial pancreas (Inreda Diabetic)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with diabetes mellitus type 1; Treated with SAP or CSII for a minimum of 6 months; 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; Use of acetaminophen during the open loop or closed loop period, as this may influence the sensor glucose measurements; Limited ability to see, and to hear or feel alarm signals of the closed loop system; Skin condition prohibiting needle insertion; Pregnancy and/or breastfeeding; Living alone during the night during the closed loop period (the patient may ask someone to stay over temporarily); Expected poor connectivity with internet regarding 24/7 tele monitoring; 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>14 days patient-managed Insulin pump therapy (with or without glucose sensor) with blinded continuous glucose monitoring | Device: Insulin pump therapy (with or without glucose sensor)<br>* Patients' own insulin pump with fast-acting insulin analog and optionally with own glucose sensor<br>* Other names: Sensor augmented pump therapy (SAP);|
| Experimental: Closed loop<br>4-6 training + 14 days automated blood glucose control with the Artificial pancreas (Inreda Diabetic) | Device: Artificial pancreas (Inreda Diabetic)<br>* Bi-hormonal reactive closed loop system without mealtime announcement<br>* Other names: Closed loop therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in target | Proportion of time spent in the target range (3.9-10 mmol/l) | Week 1-2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in hypoglycemia 1 | Proportion of time spent in hypoglycemia (<3.9 mmol/l) | Week 1-2 / Week 1 / Week 2 | 
| Time in hypoglycemia 2 | Proportion of time spent in hypoglycemia (<3.3 mmol/l) | Week 1-2 / Week 1 / Week 2 | 
| Time in hyperglycemia 1 | Proportion of time spent in hyperglycemia (>10 mmol/l) | Week 1-2 / Week 1 / Week 2 | 
| Time in hyperglycemia 2 | Proportion of time spent in hyperglycemia (>13.9 mmol/l) | Week 1-2 / Week 1 / Week 2 | 
| Hypoglycemic events | Number of carbohydrate-treated hypoglycemic events | Week 1-2 / Week 1 / Week 2 | 
| Mean or median glucose | Mean or median sensor glucose concentration | Week 1-2 / Week 1 / Week 2 | 
| Mean or median day glucose | Mean or median sensor glucose concentration | Day time: Week 1-2 / Week 1 / Week 2 | 
| Mean or median night glucose | Mean or median sensor glucose concentration | Night time: Week 1-2 / Week 1 / Week 2 | 
| Mean or median postprandial glucose | Mean or median sensor glucose concentration | Postprandial: Week 1-2 / Week 1 / Week 2 | 
| Glycemic variability 1 | Interquartile range (IQR) | Week 1-2 / Week 1 / Week 2 | 
| Glycemic variability 2 | Coefficient of variation (CV) | Week 1-2 / Week 1 / Week 2 | 
| Glycemic variability 3 | Low blood glucose index (LBGI) | Week 1-2 / Week 1 / Week 2 | 
| Glycemic variability 4 | High blood glucose index (HBGI) | Week 1-2 / Week 1 / Week 2 | 
| Glycemic variability 5 | Blood glucose risk index (BGRI) | Week 1-2 / Week 1 / Week 2 | 
| Time in target | Proportion of time spent in the target range (3.9-10 mmol/l) | Week 1 / Week 2 | 
| PAID: Problem Areas In Diabetes questionnaire | Total score; Scale 0 (no problems) to 80 (big problems) | Baseline / End week 2 | 
| EQ5D: EuroQol 5 Dimensions questionnaire | Quality of life measure; Scale 1 (no problem) to 5 (extreme problems) | Baseline / End week 2 | 
| DTSQ-status: Diabetes Treatment Satisfaction Questionnaire | Total score: Scale 0 (negative) to 36 (positive) | Baseline / End week 2 | 
| DTSQ-change: Diabetes Treatment Satisfaction Questionnaire | Change in DTSQ; Total score: Scale -18 (negative) to 18 (positive) | End week 2 | 
| Algorithm active time | Percentage of time that the closed loop algorithm is active | Week 1-2 (closed loop only) | 
| Usability score | Questionnaire: Mobile Phone Usability Questionnaire (MPUQ); Total score: Scale 62 (low level of usability) to 310 (higher level of usability) | End week 2 (closed loop only) | 
| Glucose measurement performance | MARD | Day 3, 4 or 5 of the training period prior to the closed loop | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial pancreas, Glucose control