Glycemic Outcomes and Safety With Minimed 780G System in Children With Type 1 Diabetes Aged 2-6 Years

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of advanced hybrid-closed loop system, Minimed 780G to glycemic control and safety in children aged 2-6 years with type 1 diabetes. Additionally, the study evaluates the perceived burden of the diabetes treatment to families during the advanced hybrid-closed loop system treatment (diabetes distress). This is a prospective, non-randomized, single-arm study, where primary endpoint is the change in TIR after hybrid-closed loop system initiation. Secondary endpoints are safety (number of severe hypoglycaemias and diabetic ketoacidosis, DKA), HbA1c, time below range (TBR), mean sensor glucose (SG), standard deviation of SG, and coefficient of variation (CV). The inclusion criteria are 1) TDD (total insulin daily dose) ≥ 8 units, 2) HbA1c < 10%, 3) capability to use pump and the CGM, and 4) time from diabetes diagnosis more than 6 months. The exclusion criteria are hemophilia or any other bleeding disorder, a condition, which in the opinion of the investigator would put the participant at risk during the trial.

Detailed Description
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BACKGROUND The treatment of small children's type 1 diabetes (T1D) is challenging. There is often great day-to-day and within-day variability in glucose levels and HbA1c targets are hard to achieve. The results on hybrid closed loop systems (HCL) in children have been encouraging, suggesting that an algorithm, which automatically doses basal insulin based on sensor glucose (SG) levels, improves time in range (TIR) (3.9-10 mmol/l / 71-180 mg/dl) and reduces the time spent below range (TBR). Despite of these improvements, the target level of TIR (70%) has not been reached in these studies. In pivotal studies, Minimed 780G advanced HCL system has helped children over 7 years old to reach higher TIR and improve mealtime glycaemia without increasing TBR, severe hypoglycaemias or ketoacidosis. This study evaluates the effectiveness to glycemic control and safety of advanced hybrid-closed loop system, Minimed 780G, in children aged between 2.0-6.99 years, with type 1 diabetes. The study protocol is explained to the participants (2.0-6.99 year-old children) orally. Informed consent from participants' caregivers and those participants who can write will be taken by investigators, clinicians or diabetes nurses. The investigator will explain the nature of the study to the subject, and answer all questions regarding this study. Prior to any study-related screening procedures being performed on the participant, the informed consent statement will be reviewed and signed and dated by participant's caregiver. STUDY PROTOCOL The study includes a two week run-in-phase in open loop Manual mode, which equals for standard sensor augmented pump (SAP) treatment (this feature is also in the same device), which is followed by a three month study phase with advanced hybrid closed loop Auto mode. The participants will be given an advanced HCL pump (MiniMed 780G™ system with SmartGuard Medtronic, Northridge, CA). Minimed 780g™ is an insulin pump, which doses insulin automatically to patients subcutaneous tissue every 5 minutes based on SG values. The maximal dosing is based on participants TDD. The SmartGuard feature uses meal information, up to date SG reading, and SG target values to control basal insulin delivery. Additionally, it can automatically deliver a correction bolus to correct a high SG reading. The MiniMed 780G insulin pump requires a minimum of eight units and a maximum of 250 units per day to operate using the SmartGuard feature (Medtronic Minimed 780g™ system user guide). This device has CE mark and is indicated to children aged over 7 years who require insulin over 8 units/day. In manufacturers safety studies, no adverse effects (diabetic ketoacidosis (DKA) or severe hypoglycaemias) has been reported in children over 7 years old who had TDD over 8 units/day (MDT personal communication). The infusion set of insulin pump is changed every 2-3 days by patients' caregivers. The material connected to subcutaneous tissue is Teflon. The SG values are measured by continuous glucose monitor (CGM). The used CGM is Guardian3 sensor, which is integrated to Minimed 780g™ system. It measures the glucose level in the subcutaneous tissue. The CGM sensor connects to a transmitter that sends the glucose data to insulin pump. The sensor is worn for 7 days and then replaced with a new one by the participants' caregivers. The traceability is achieved by each device's serial number (insulin pump, CGM transmitter). The glucose sensors, infusion sets, reservoirs and glucose sensors have lot numbers. The families are trained to use the device by Medtronic's local representatives (technical issues), diabetes nurses, and clinicians (dosing and other medical issues). If the family has been on a sensor augmented pump (SAP) treatment previously, training includes one 3 hour session, a normal procedure in our clinic, at the outpatient clinic. If family has no previous experience on pump treatment or CGM, they will first try CGM out for 2 weeks and then 3-days visit on day hospital is arranged to first learn the basics on insulin pump treatment. POWER ANALYSES Based on previous studies, it was estimated that a significant difference in increased TIR between the advanced HCL treatment and the Manual mode would be 10% and the standard deviation is expected to be 13%. Taken these into account, the power of 90% to detect a difference between the modes with type 1 error rate of 0.05, 35 participants should complete the protocol. The dropout rate is estimated to be less than 3%, thus 38 HCL systems have been reserved for 38 participants. ETHICAL ISSUES This study is conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki. This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the International Conference on Harmonization (ICH) and in accordance with the ethical principles underlying European Union Directive 2001/20/EC and 2005/28/EC (or Regulation (EU) No 536/2014). The ethics committee of Helsinki University Hospital and The Finnish Medicines Agency has approved the study protocol.

Official Title
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Glycemic Outcomes and Safety With Minimed 780G System in Children With Type 1 Diabetes Aged 2-6 Years

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Medronic 780G insulin pump


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: total insulin daily dose ≥ 8 units HbA1c < 10% capability to use pump and the CGM time from diabetes diagnosis more than 6 months Exclusion Criteria: hemophilia or any other bleeding disorder, a condition, which in the opinion of the investigator would put the participant at risk during the trial

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 6 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hybrid closed loop system<br>Initiation of 780G insulin pump. First two weeks run-in-phase in open loop Manual mode, followed by a12 month study phase with advanced hybrid closed loop Auto mode. | Device: Medronic 780G insulin pump<br>* Commercial hybrid closed loop system Medronic 780G<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in range (glucose between 3.9-10 mmol/l) before and during hybrid close loop insulin pump treatment | Time in range (%) derived from continuous glucose monitoring | Up to 3 months | 
| Time in range (glucose between 3.9-10 mmol/l) before and during hybrid close loop insulin pump treatment | Time in range (%) derived from continuous glucose monitoring | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of severe hypoglycemia before and during hybrid close loop insulin pump treatment | Number of hypoglycemia (glucose <3.0 and altered mental status) derived from blood glucose monitoring | Up to 3 months | 
| The number of severe hypoglycemia before and during hybrid close loop insulin pump treatment | Number of hypoglycemia (glucose <3.0 and altered mental status) derived from blood glucose monitoring | Up to 12 months | 
| Number of diabetic ketoacidosis in participant before and during hybrid close loop insulin pump treatment | Number of diabetes ketoacidosis derived from patient information system | Up to 3 months | 
| Number of diabetic ketoacidosis in participant before and during hybrid close loop insulin pump treatment | Number of diabetes ketoacidosis derived from patient information system | Up to 12 months | 
| Diabetes distress before and during hybrid close loop insulin pump treatment | Parents diabetes distress measured with validated questionnaire: Problem Areas In Diabetes-Parent Revised (PAID-Pr) (scored 0-72) | Up to 3 months | 
| Diabetes distress before and during hybrid close loop insulin pump treatment | Parents diabetes distress measured with validated questionnaire: Problem Areas In Diabetes-Parent Revised (PAID-Pr) (scored 0-72) | Up to 12 months | 
| HbA1c before and during hybrid close loop insulin pump treatment | HbA1c (mmol/mol, %) measured from blood during treatment | Up to 3 months | 
| HbA1c before and during hybrid close loop insulin pump treatment | HbA1c (mmol/mol, %) measured from blood during treatment | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hybrid closed loop system