Effect of Automated Insulin Delivery on Early-stage Diabetic Complications

Study Overview
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Brief Summary
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Aim of this study is to verify the effects of an advanced HCL (Medtronic Minimed™ 780G) compared to SAP with PLGS on metabolic outcomes and markers of early microvascular damage in a population of adults with T1D previously treated with CSII. Evaluation of endothelial disfunction and autonomic neuropathy will also be performed.

Detailed Description
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New algorithms for the automation of insulin delivery (AID) are showing great benefit on glucose control in people with type 1 diabetes. Indeed, Hybrid closed loop (HCL) systems can improve HbA1c levels, percentage of time in defined glucose range, time below range and time over range, according to RCT and observational studies results. However, scientific evidences demonstrating potential benefits on the reduction of diabetes complications are limited regarding CSII or SAP with demonstrated reduction of cardiovascular mortality, improvement of albuminuria and peripheral nerve damage. Data on AID effects on complications of diabetes are missing. In this study intermediate damage markers will be measured to assess potential effects of AID in comparison to sensor augmented pumps.

Official Title
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Effect of Automated Insulin Delivery With Advanced Closed-loop on Glucose Outcomes and Early-stage Diabetic Complications

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Medtronic MiniMed 780G with SmartGuard activation
* Device: Medtronic MiniMed 780G without SmartGuard activation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients T1D patients above 18 years in CSII treatment for at least 3 months HbA1c values between 6.0% and 9.5% Disease duration ≥ 2 years Written informed consent obtained from the patient Exclusion Criteria: Pregnancy Participation to other clinical trials A history of alcohol or drug abuse Advanced diabetic nephropathy defined as presence of albuminuria ≥ 300 mg/g or eGFR < 60 ml/min/1,73m2 Proliferative Diabetic retinopathy or macular edema Established Atherosclerotic Cardiovascular Disease (ASCVD) or history of heart failure Presence of serious diseases or conditions which in the opinion of the Investigator makes patient non-eligible for the study Hypoglycemia Unawareness (Clarke score > 4) Patients unable to understand spoken and written Italian language

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open label randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study Group A (Intervention)<br>Group treated with automated insulin delivery (advanced hybrid closed-loop) | Device: Medtronic MiniMed 780G with SmartGuard activation<br>* Insulin pump implemented with alghoritm for automatic modulation of insulin delivery (to increase time in glucose range 70-180 mg/dl)<br>|
| Active Comparator: Study Group B (Control)<br>Group treated with predictive low glucose suspend (sensor augmented pump - PLGS) | Device: Medtronic MiniMed 780G without SmartGuard activation<br>* Insulin pump implemented with alghoritm for low glucose insulin suspension (to reduce hypoglycemia rate)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in glycemic range 70-180 mg/dl | time spent by the patient in glucose range | From Baseline to 26 weeks | 
| Glycated Hemoglobin (HbA1c) | percentage of hemoglobin glycosylated | From Baseline to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early microangiopathic damage markers: sTNFR-1/2 | sTNFR-1/2 (pg/ml) | From Baseline to 26 weeks | 
| Early microangiopathic damage markers: B-2 microglobulin | B-2 microglobulin (pg/ml) | From Baseline to 26 weeks | 
| Early microangiopathic damage markers: cystatin C | cystatin C (ng/ml) | From Baseline to 26 weeks | 
| Early microangiopathic damage markers: neutrophil gelatinase-associated lipocalin | neutrophil gelatinase-associated lipocalin (ng/ml) | From Baseline to 26 weeks | 
| Early microangiopathic damage markers: osteopontin | osteopontin (pg/ml) | From Baseline to 26 weeks | 
| Early microangiopathic damage markers: vWF levels | vWF levels (ng/ml) | From Baseline to 26 weeks | 
| Endothelial disfunction | Endothelial-dependent dilation (EDD) is considered a marker of dysfunctional abnormalities involved in early phases of atherosclerosis development. Changes in EDD precede structural changes and occurs in the preclinical phase of vascular disease. In the present study endothelial dependent dilation is assessed by color Doppler evaluation of flow increase after hyperemia. | From Baseline to 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Automated insulin delivery, Type 1 Diabetes complications