Closed-loop Control of Glucose Levels (Artificial Pancreas) for 5 Days in Adults With Type 1 Diabetes

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. The main objective of this project is to compare the efficacy of single-hormone closed-loop strategy and sensor-augmented pump therapy to regulate glucose levels in outpatient settings for 5 consecutive days in adults with type 1 diabetes. The investigators hypothesized that single-hormone closed-loop strategy will increase the time spent in the target range compared to sensor-augmented pump therapy.

Official Title
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An Open-label, Randomized, Two-way, Cross-over Study to Assess the Efficacy of Single-hormone Closed-loop Strategy and Sensor-augmented Pump Therapy in Regulating Glucose Levels for 5 Days in Free-living Outpatient Conditions in Patients With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: 5-day intervention with single-hormone closed-loop strategy
* Other: 5-day intervention with sensor-augmented pump therapy
* Device: Insulin pump
* Device: Continuous glucose monitoring system
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 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 ≤ 10%. Live in the area of Montreal. Exclusion Criteria: Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery. Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding) Pregnancy (ongoing or current attempt to become pregnant). Severe hypoglycemic episode within two weeks of screening. Current use of glucocorticoid medication (except low stable dose and inhaled steroids). 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. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sensor-augmented pump therapy<br>Participants will use sensor-augmented pump therapy with low-glucose suspend to regulate glucose levels. The low-glucose suspend feature available in the MiniMed® Paradigm® Veo™, Medtronic combined with the Enlite sensor® will be used. This feature allows for suspension of insulin delivery at a pre-set sensor glucose value for up to 2 hours. | Other: 5-day intervention with sensor-augmented pump therapy<br>* A sensor will be inserted on the day prior to the first day of the intervention by the participants. The participant will also have to install the study insulin pump. Participants will be advised to continue with study intervention at home for the next 5 days. Participants will have been previously shown how to use the study insulin pump.<br>Device: Insulin pump<br>* MiniMed® Paradigm® Veo™, Medtronic<br>Device: Continuous glucose monitoring system<br>* Enlite sensor®, Medtronic<br>Drug: Insulin<br>* Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)<br>|
| Active Comparator: Single-hormone closed-loop strategy<br>Variable subcutaneous insulin infusion will be used to regulate glucose levels. Participant's usual fast-acting insulin analog will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump. | Other: 5-day intervention with single-hormone closed-loop strategy<br>* A sensor will be inserted on the day prior to the first day of the intervention by the participants. On the first day of the intervention, participants will be admitted to the clinical research facility anytime between 8:00 am and 11:30 am. Training on connection and disconnection of the system, meal boluses, etc. will be given. Competency on the use of study devices will be assessed by a team member. Only participants demonstrating competency on use of study devices will be allowed to continue to the home study phase. Participants will be advised to continue with study intervention at home for the next 5 days.<br>Device: Insulin pump<br>* MiniMed® Paradigm® Veo™, Medtronic<br>Device: Continuous glucose monitoring system<br>* Enlite sensor®, Medtronic<br>Drug: Insulin<br>* Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)<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 between 3.9 and 10.0 mmol/L |  | 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L |  | 120 hours | 
| Percentage of time of glucose levels spent below 3.9 mmol/L |  | 120 hours | 
| Percentage of time of glucose levels spent below 3.3 mmol/L |  | 120 hours | 
| Percentage of time of glucose levels spent below 2.8 mmol/L |  | 120 hours | 
| Percentage of time of glucose levels spent above 10 mmol/L |  | 120 hours | 
| Percentage of time of glucose levels spent above 13.9 mmol/L |  | 120 hours | 
| Percentage of time of glucose levels spent above 16.7 mmol/L |  | 120 hours | 
| Percentage of time of overnight glucose levels spent below 3.9 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent between 3.9 and 7.8 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent between 3.9 and 10.0 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent below 3.3 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent below 2.8 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent above 10 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent above 13.9 mmol/L |  | 35 hours | 
| Percentage of time of overnight glucose levels spent above 16.7 mmol/L |  | 35 hours | 
| Area under the curve of glucose levels below 3.9 mmol/L |  | 120 hours | 
| Area under the curve of glucose levels below 3.3 mmol/L |  | 120 hours | 
| Area under the curve of glucose levels below 2.8 mmol/L |  | 120 hours | 
| Area under the curve of glucose levels above 10 mmol/L |  | 120 hours | 
| Area under the curve of glucose levels above 13.9 mmol/L |  | 120 hours | 
| Area under the curve of glucose levels above 16.7 mmol/L |  | 120 hours | 
| Area under the curve of overnight glucose levels below 3.9 mmol/L |  | 35 hours | 
| Area under the curve of overnight glucose levels below 3.3 mmol/L |  | 35 hours | 
| Area under the curve of overnight glucose levels below 2.8 mmol/L |  | 35 hours | 
| Area under the curve of overnight glucose levels above 10 mmol/L |  | 35 hours | 
| Area under the curve of overnight glucose levels above 13.9 mmol/L |  | 35 hours | 
| Area under the curve of overnight glucose levels above 16.7 mmol/L |  | 35 hours | 
| Mean glucose levels |  | 120 hours | 
| Standard deviation of glucose levels |  | 120 hours | 
| Standard deviation of insulin delivery |  | 120 hours | 
| Coefficient of variance of glucose levels |  | 120 hours | 
| Coefficient of variance of insulin delivery |  | 120 hours | 
| Between-day variability in glucose levels |  | 120 hours | 
| Between-day variability in insulin delivery |  | 120 hours | 
| Total insulin delivery |  | 120 hours | 
| Percentage of time of closed-loop operation |  | 120 hours | 
| Percentage of time of glucose sensor availability |  | 120 hours | 
| Time between failures | Total hours of closed-loop operation over number of failures | 120 hours | 
| Number of hypoglycemic events less than 3.1 mmol/L |  | 120 hours | 
| Number of nights with hypoglycemic events less than 3.1 mmol/L |  | 35 hours | 
| Number of days with hypoglycemic events less than 3.1 mmol/L |  | 120 hours | 

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