Effect of CGM With Predictive Alarm on Hypoglycemia in Young Patients With T1D.

Study Overview
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Brief Summary
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The use of continuous glucose monitoring (CGM) is becoming the new standard in glycometabolic control in patients with Type 1 Diabetes Mellitus (T1DM) even in subjects in multiple daily insulin injections (MDI). Compared to self-monitoring of blood glucose (SMBG), the CGM systems allow continuous monitoring of the glycemic trends contributing to modify the therapeutic habits of adult and pediatric patients with T1DM and allowing to better managing of critical situations such as hypoglycemia. Recently, the accuracy and reliability performance of the latest generation of CGMs using predictive alarm for hypoglycaemia and hyperglycemia has been compared to other commercially available CGM systems, showing good levels of concordance. The use of this new technology, through the continuous monitoring of the pre-and post-prandial glucose levels and the evaluation of the glycemic trends, could influence the therapeutic habits of patients and could substantially contribute to modifying insulin therapy. Furthermore, the presence of the predictive alarm technology for hypoglycemia could lead to reduce the number of hypoglycemic episodes and to modify the way these hypoglycemic episodes are managed; moreover, the use of this technology could improve the time spent in the target glycemic range [Time in Range (TIR), 70-180 mg/dl] with possible improvement also in glycemic variability control.

Official Title
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Impact of Continuous Glucose Monitoring (CGM) With Predictive Alarm for Hypoglycemia (Guardian Connect System) on Glycemic Control and Hypoglycemia Management in a Group of Adolescents With Type 1 Diabetes Mellitus Treated With Multiple Daily Insulin Injections (MDI).

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Use of Predictive Alarm for hypoglycaemia or hyperglycaemia
* Device: Use of Alarm on Threshold for hypoglycaemia or hyperglycaemia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1DM for at least 12 months [assessed by positivity of at least one of the antibodies against islet cells (ICA), insulin (IAA), glutamate dehydroxylase (GADA), islet antigen 2 (IA2A), or Zinc Transporter 8 Antibodies (ZnT8)]; MDI therapy from at least 6 months with basal-bolus treatment (long acting insulin analog plus rapid acting insulin analogue); HbA1c < 9.0% normal weight (BMI <85th percentile for age and gender); no other chronic diseases (thyroiditis, celiac disease, etc) or eating behavior disorders (DCA); signed informed consent from parents or legal guardians and patients (<18 y). Exclusion Criteria: T1DM for less than 12 months; CSII therapy Previous usage of CGM with predictive alarm for hypoglycemia or hyperglycemia MDI therapy from less than 6 months use of regular insulin instead of rapid acting insulin analogue; other chronic diseases (thyroiditis, celiac disease, etc.) or eating behavior disorders (DCA).

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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
Interventional Model Description: This is a crossover, monocentric and randomized study with a post-market medical device.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Predictive Alarm (PA)<br>Patients use the CGM sensor with Predictive Alarm on set at 70 mg/dl in 20 minutes for hypoglycemia and at 250 mg/dl in 20 minutes for hyperglycemia. | Device: Use of Predictive Alarm for hypoglycaemia or hyperglycaemia<br>* Patients use CGM sensor with Predictive Alarm set at 70 mg/dl in 20 minutes for hypoglycemia and at 250 mg/dl in 20 minutes for hyperglycemia. in case of alarm from the hypoglycemia predictive algorithm, the indicated treatment was 0.1g of sugar/kg of body weight; in case of alarm from the hyperglycemia predictive algorithm, the indication was to give an extra shot of rapid-acting insulin. The dose will be calculated on the basis of personal insulin sensitivity factor (ISF), considering as target a blood glucose of 120 mg/dl and 250 mg/dl as the projected blood glucose level that will be reached in 20 minutes. This could be done only if there is no active insulin on-board, after at least 3 hours from the last rapid-acting insulin injection.<br>|
| Active Comparator: Alarm on Threshold (AoT)<br>Patients use the CGM sensor with alarms on a threshold of 70 mg/dl for hypoglycemia and 250 mg/dl for hyperglycemia. | Device: Use of Alarm on Threshold for hypoglycaemia or hyperglycaemia<br>* in case of alarm of hypoglycemia, the indicated treatment was 0.3g of sugar/kg of body weight, max 15g. in case of alarm of hyperglycemia, the indication will be to give an extra shot of rapid-acting insulin. The dose will be calculated on the basis of personal insulin sensitivity factor (ISF), considering as target a blood glucose of 120 mg/dl and 250 mg/dl as blood glucose level to correct. This could be done only if there is no active insulin on-board, after at least 3 hours from the last rapid-acting insulin injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Less time spent in hypoglycaemia using Predictive Alarm vs Alarm on Threshold | the difference in the percentage of time spent below 70 mg/dl (TBR < 70 mg/dl) between the Alarm on Threshold (AoT) and the Predictive Alarm (PA) arms after 2 weeks of treatment | 2 weeks CGM data with PA vs 2 weeks CGM data with AoT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Better glycemic metrics using Predictive Alarm vs Alarm on Threshold | the difference in the percentage of time spent in 70-180 mg/dl range (TIR) between the Alarm on Threshold (AoT) and Predictive Alarm (PA) arms after 2 weeks of treatment (V2 vs V1 and V4 vs V3); the difference in the percentage of time spent above 250 mg/dl (TAR > 250 mg/dl) between the Alarm on Threshold and Predictive Alarm arms after 2 weeks of treatment (V2 vs V1 and V4 vs V3). the difference in main glucose metrics (%TIR, %TBR, %TAR) and glucose variability measures (SD, %CV, MAG, MAGE, HBGI, LBGI, ADRR, CONGA, MODD) between Group A (PA/AoT) and Group B (AoT/PA) at the end of the treatment period (V4) vs baseline (V1) | 2 weeks CGM data with PA vs 2 weeks CGM data with AoT |