Closed-loop Control of Overnight Glucose Levels (Artificial Pancreas) in Children With Type 1 Diabetes in a Diabetes Camp

Study Overview
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Brief Summary
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Closed-loop strategy is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosages based on the sensor's readings. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormone: insulin and glucagon. The main objective of this project is to compare the efficacy of single-hormone closed-loop strategy, dual-hormone closed-loop strategy and pump therapy to regulate overnight glucose levels in children with type 1 diabetes in a diabetes camp. The investigators hypothesized that dual-hormone closed-loop strategy reduces the time spent in hypoglycemia in children with type 1 diabetes (T1D) compared to single-hormone closed-loop strategy, which in turn is more effective than the conventional pump therapy to reduce time spent in hypoglycemia

Detailed Description
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Closed-loop strategy is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosages based on the sensor's readings. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormone: insulin and glucagon. The investigators aim to conduct a randomized three-way cross-over trial comparing single hormone closed-loop strategy, dual-hormone closed-loop strategy and the conventional pump therapy. The investigators aim to compare the three interventions for 3 consecutive nights in children with type 1 diabetes in a diabetes camp.

Official Title
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An Open-label, Randomized, Three-way, Cross-over Study to Assess the Efficacy of Single-hormone Closed-loop Strategy, Dual-hormone Closed-loop Strategy and Conventional Pump Therapy in Regulating Overnight Glucose Levels in Children With Type 1 Diabetes in a Diabetes Camp

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Single-hormone closed-loop strategy
* Device: Dual-hormone closed-loop strategy
* Device: Insulin pump therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the 8 and 17 years of old. Clinical diagnosis of type 1 diabetes for at least one year. The subject will have been on insulin pump therapy for at least 3 months. HbA1c ≤ 11.0%. Exclusion Criteria: Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator. Severe hypoglycemic episode within two weeks of inclusion in the study. A severe hypoglycemic episode is defined as loss of conscience, seizure or a hospital emergency visit. Current use of oral glucocorticoid medication (except low stable dose according to investigator judgement). Stable doses of inhaled steroids are acceptable. Known or suspected allergy to the trial products. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator. Failure to comply with team's recommendations (e.g. not willing to use trial pump, etc).

Ages Eligible for Study
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Minimum Age: 8 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin pump therapy<br>Glucose levels will be controlled for 3 consecutive nights using insulin pump therapy. Subjects will carry on with their normal conventional insulin pump therapy and will be allowed to freely implement therapeutic adjustments.. | Device: Insulin pump therapy<br>* Subjects will use conventional pump therapy to regulate glucose levels. Insulin Aspart (Novorapid, Novo Nordisk) will be used.<br>|
| Active Comparator: Single-hormone closed-loop strategy<br>Glucose levels will be controlled by single-hormone closed-loop strategy for 3 consecutive nights. A member of the research team will be present at the diabetic camp to ensure protocol implementation and patient's safety. Glucose levels will be controlled by single-hormone closed-loop strategy between 22:00 until 7:00 next morning. Glucose sensor reading will be entered manually into the computer every 10 minutes. The computer will generate a recommendation for the basal rates of insulin delivery. Pump's parameters will then be changed manually to implement the computer generated recommendations. | Device: Single-hormone closed-loop strategy<br>* Variable subcutaneous insulin infusion rates will be used to regulate glucose levels. Insulin Aspart (Novorapid, Novo Nordisk) will be used.<br>|
| Active Comparator: Dual-hormone closed-loop strategy<br>Glucose levels will be controlled by dual-hormone closed-loop strategy for 3 consecutive nights. A member of the research team will be present at the diabetic camp to ensure protocol implementation and patient's safety. Glucose levels will be controlled by dual-hormone closed-loop strategy between 22:00 until 7:00 next morning. Glucose sensor readings will be entered manually into the computer every 10 minutes. The computer will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses. Pumps' parameters will then be changed manually to implement the computer generated recommendations. | Device: Dual-hormone closed-loop strategy<br>* Variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels. Insulin Aspart (Novorapid, Novo Nordisk) and Glucagon (Eli Lilly and Company) will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time of glucose levels spent below 4.0 mmol/L. |  | Up to 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time of glucose levels spent between 4.0 and 8.0 mmol/L |  | Up to 8 hours | 
| Percentage of time of glucose levels spent below 3.5 mmol/L |  | Up to 8 hours | 
| Percentage of time of glucose levels spent below 3.3 mmol/L |  | Up to 8 hours | 
| Percentage of time of glucose levels spent above 8 mmol/L |  | Up to 8 hours | 
| Percentage of time of glucose levels spent above 10 mmol/L. |  | Up to 8 hours | 
| Area under the curve of glucose levels below 4.0 mmol/L |  | Up to 8 hours | 
| Area under the curve of glucose levels below 3.5 mmol/L |  | Up to 8 hours | 
| Area under the curve of glucose levels below 3.3 mmol/L |  | Up to 8 hours | 
| Area under the curve of glucose levels above 8.0 mmol/L |  | Up to 8 hours | 
| Area under the curve of glucose levels above 10.0 mmol/L. |  | Up to 8 hours | 
| Mean glucose levels. |  | Up to 8 hours | 
| Standard deviation of glucose levels | Measure of glucose variability. | Up to 8 hours | 
| Total insulin delivery |  | Up to 8 hours | 
| Hypoglycemic risk assessed by the total number of hypoglycemic event (> 15 minutes) below 3.1 mmol/L |  | Up to 8 hours | 
| Hypoglycemic risk assessed by the number of patients experiencing at least one hypoglycemic event (> 15 minutes) below 3.1 mmol/L |  | Up to 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes, Hypoglycemia, Insulin, Glucagon, Closed-loop system, Artificial pancreas