Closed-loop Control of Glucose Levels (Artificial Pancreas) for 12 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 objective of this study is to compare the effectiveness of single-hormone closed-loop and sensor-augmented pump therapy in regulating day-and-night glucose levels in adults with T1D for 12 days in outpatient settings. The investigators hypothesize that dual-hormone closed-loop will increase the percentage of time of glucose levels spent in the target range in adults compared to single-hormone closed-loop, which in turn will be more effective than 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 12 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: 12-day intervention with sensor-augmented pump therapy
* Other: 12-day intervention with single-hormone closed-loop strategy
* 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 ≤ 12%. 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) Chronic use of acetaminophen. Acetaminophen may interfere with glucose sensor readings Pregnancy (ongoing or current attempt to become pregnant) Breastfeeding No nearby party for assistance if needed Plans to go abroad or travel at more than 2 hours distance from Montreal during the trial period Severe hypoglycemic episode within two weeks of screening or during the run-in period Severe hyperglycemic episode requiring hospitalization in the last 3 months 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 Anticipation of a significant change in exercise regimen between admission and end of the trial (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: 12-day intervention with sensor-augmented pump therapy<br>* A sensor will be inserted on the day before the start 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 12 days. Participants will have been previously shown how to use the study insulin pump.<br>Device: Insulin pump<br>* Tandem Diabetes Care<br>Device: Continuous glucose monitoring system<br>* Dexcom G5 Platinum<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: 12-day intervention with single-hormone closed-loop strategy<br>* A sensor will be inserted on the day before the start 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. 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 12 days.<br>Device: Insulin pump<br>* Tandem Diabetes Care<br>Device: Continuous glucose monitoring system<br>* Dexcom G5 Platinum<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 mmol/L. |  | 288 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 |  | 288 hours | 
| Percentage of time of glucose levels spent below 3.9 mmol/L |  | 288 hours | 
| Percentage of time of glucose levels spent below 3.3 mmol/L |  | 288 hours | 
| Percentage of time of glucose levels spent below 2.8 mmol/L |  | 288 hours | 
| Percentage of time of glucose levels spent above 10.0 mmol/L |  | 288 hours | 
| Percentage of time of glucose levels spent above 13.9 mmol/L |  | 288 hours | 
| Percentage of time of glucose levels spent above 16.7 mmol/L |  | 288 hours | 
| Percentage of time of overnight glucose levels spent between 3.9 and 7.8 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent between 3.9 and 10.0 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent below 3.9 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent below 3.3 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent below 2.8 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent above 10.0 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent above 13.9 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Percentage of time of overnight glucose levels spent above 16.7 mmol/L | The overnight period is between 00:00 and 06:00 | 72 hours | 
| Total number of hypoglycemic events below 3.1 mmol/L |  | 288 hours | 
| Number of nights with hypoglycemic events below 3.1 mmol/L |  | 72 hours | 
| Number of days with hypoglycemic events below 3.1 mmol/L |  | 126 hours | 
| Mean glucose levels |  | 288 hours | 
| Standard deviation of glucose levels |  | 288 hours | 
| Time between failures due to glucose sensor unavailability |  | 288 hours | 
| Coefficient of variation of glucose levels |  | 288 hours | 
| Between-day variability in glucose levels |  | 288 hours | 
| Total daily insulin dose |  | 24 hours | 
| Standard deviation of insulin delivery |  | 288 hours | 
| Coefficient of variation of insulin delivery |  | 288 hours | 
| Between-day variability in insulin delivery |  | 288 hours | 
| Total number of hours of glucose sensor availability |  | 288 hours | 
| Percentage of time of glucose sensor availability |  | 288 hours | 
| Time between failures due to pump connectivity |  | 288 hours | 
| Percentage of time when patients switched back to insulin pump therapy |  | 288 hours | 
| Number of hours when patients switched back to insulin pump therapy |  | 288 hours | 
| Percentage of time when the closed-loop was automatically switched to insulin pump therapy |  | 288 hours | 
| Number of hours when the closed-loop was automatically switched to insulin pump therapy |  | 288 hours | 
| Number of days with at least one technical problem |  | 288 hours | 
| Number of calls for technical issues related to the closed-loop system |  | 288 hours | 
| Number of patients calling for technical issues related to the closed-loop system |  | 288 hours | 

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