Comparison of the Efficacy of Rapid-acting Aspart and Faster Acting Aspart Within the Context of Single-hormone Closed-loop Strategy at Regulating Postprandial Glucose Levels

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 pilot study is to inform both the decision whether to conduct a confirmatory study and the design of the larger confirmatory trial. In addition, we want to estimate postprandial glucose levels parameters and confidence interval in an 11-hour in-patient study with standardized conditions in adults with type 1 diabetes, estimate the size and direction of the treatment effect. Faster insulin Aspart (FiAsp) will provide preliminary evidence of efficacy to regulate postprandial glucose levels compared to rapid-acting Aspart in adults with type 1 diabetes using insulin pump therapy.

Official Title
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An Open-label, Double-blind, Randomized, Two-way, Cross-over Pilot Study to Provide Preliminary Evidence of the Efficacy of Rapid-acting Aspart Compared to Faster Acting Aspart Within the Context of Single-hormone Closed-loop Strategy at Regulating Postprandial Glucose Levels in Adults With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: Insulin pump
* Device: Continuous glucose monitoring system
* Other: 11-hour intervention with the single-hormone artificial pancreas


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 6 months. HbA1c ≤ 12%. Exclusion Criteria: Using a patch-pump (e.g. Omnipod) 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. Ongoing or planned pregnancy. Breastfeeding. Severe hypoglycemic episode within two weeks of screening. Current use of glucocorticoid medication (except low stable dose and inhaled stable treatment). Known or suspected allergy to the trial products or meal contents. 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 eat meals/snacks, not willing to change pump parameters, etc). Problems with venous access.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rapid-acting Aspart<br>Rapid-acting Aspart will be used to regulate glucose levels | Device: Insulin pump<br>* The participant's insulin pump will be used to infuse insulin<br>Device: Continuous glucose monitoring system<br>* The Dexcom G4 Platinum will be used to measure glucose levels<br>Other: 11-hour intervention with the single-hormone artificial pancreas<br>* Subjects will be admitted at IRCM at 9:30. An intravenous catheter will be inserted into an arm or a hand vein for blood sampling purposes. A cartridge containing rapid-acting Aspart or faster acting Aspart will be placed in the insulin pump. Closed-loop strategy will start at 10:00 until 21:00. A 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. Pumps' parameters will then be changed manually to implement the computer generated recommendations. At 12:00, a lunch meal will be served. An insulin bolus will be given 15 minutes before the meal. At 17:00, a dinner meal will be served. As recommended, an insulin bolus will be given at the time of the meal. Each subject will ingest the same meals during both visits. Venous blood samples will be obtained for the measurement of plasma glucose and insulin concentrations. Blood samples will be taken every 20 minutes.<br>|
| Active Comparator: Faster insulin Aspart<br>Faster insulin Aspart will be used to regulate glucose levels | Device: Insulin pump<br>* The participant's insulin pump will be used to infuse insulin<br>Device: Continuous glucose monitoring system<br>* The Dexcom G4 Platinum will be used to measure glucose levels<br>Other: 11-hour intervention with the single-hormone artificial pancreas<br>* Subjects will be admitted at IRCM at 9:30. An intravenous catheter will be inserted into an arm or a hand vein for blood sampling purposes. A cartridge containing rapid-acting Aspart or faster acting Aspart will be placed in the insulin pump. Closed-loop strategy will start at 10:00 until 21:00. A 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. Pumps' parameters will then be changed manually to implement the computer generated recommendations. At 12:00, a lunch meal will be served. An insulin bolus will be given 15 minutes before the meal. At 17:00, a dinner meal will be served. As recommended, an insulin bolus will be given at the time of the meal. Each subject will ingest the same meals during both visits. Venous blood samples will be obtained for the measurement of plasma glucose and insulin concentrations. Blood samples will be taken every 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma glucose levels 1 hour after the meal |  | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of plasma glucose levels for the 1-hour period following the meal. |  | 1 hour | 
| Area under the curve of plasma glucose levels for the 2-hour period following the meal. |  | 2 hours | 
| Plasma glucose level 1 hour after the meal. |  | 1 hour | 
| Plasma glucose level 2 hours after the meal. |  | 2 hours | 
| Glycemic peak in the 3 hours following the meal. |  | 3 hours | 
| Change in plasma glucose levels 2 hours after the meal. |  | 2 hours | 
| Peak time of glucose levels over the 4 hours following the meal. |  | 4 hours | 
| Number of hypoglycemic events less than 4.0 mmol/L over the 4 hours following the meal. |  | 4 hours | 
| Percentage of time of plasma glucose levels between 3.9 and 7.8 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels between 3.9 and 7.8 mmol/L. |  | 11 hours | 
| Percentage of time of plasma glucose levels between 3.9 and 10 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels between 3.9 and 10 mmol/L. |  | 11 hours | 
| Percentage of time of plasma glucose levels below 3.9 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels below 3.9 mmol/L. |  | 11 hours | 
| Percentage of time of plasma glucose levels below 3.3 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels below 3.3 mmol/L. |  | 11 hours | 
| Percentage of time of plasma glucose levels below 2.8 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels below 2.8 mmol/L. |  | 11 hours | 
| Percentage of time of plasma glucose levels above 10 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels above 10 mmol/L. |  | 11 hours | 
| Percentage of time of plasma glucose levels above 13.9 mmol/L |  | 11 hours | 
| Percentage of time of sensor glucose levels above 13.9 mmol/L |  | 11 hours | 
| Percentage of time of plasma glucose levels above 16.7 mmol/L. |  | 11 hours | 
| Percentage of time of sensor glucose levels above 16.7 mmol/L. |  | 11 hours | 
| Area under the curve of plasma glucose levels below 3.9 mmol/L. |  | 11 hours | 
| Area under the curve of sensor glucose levels below 3.9 mmol/L. |  | 11 hours | 
| Area under the curve of plasma glucose levels below 3.3 mmol/L. |  | 11 hours | 
| Area under the curve of sensor glucose levels below 3.3 mmol/L. |  | 11 hours | 
| Area under the curve of plasma glucose levels below 2.8 mmol/L. |  | 11 hours | 
| Area under the curve of sensor glucose levels below 2.8 mmol/L. |  | 11 hours | 
| Area under the curve of plasma glucose levels above 10.0 mmol/L. |  | 11 hours | 
| Area under the curve of sensor glucose levels above 10.0 mmol/L. |  | 11 hours | 
| Area under the curve of plasma glucose levels above 13.9 mmol/L. |  | 11 hours | 
| Area under the curve of sensor glucose levels above 13.9 mmol/L. |  | 11 hours | 
| Area under the curve of plasma glucose levels above 16.7 mmol/L. |  | 11 hours | 
| Area under the curve of sensor glucose levels above 16.7 mmol/L. |  | 11 hours | 
| Standard deviation of plasma glucose levels. |  | 11 hours | 
| Standard deviation of sensor glucose levels. |  | 11 hours | 
| Coefficient of variance of plasma glucose levels. |  | 11 hours | 
| Coefficient of variance of sensor glucose levels. |  | 11 hours | 
| Total insulin delivery. |  | 11 hours | 
| Mean plasma glucose level. |  | 11 hours | 
| Mean sensor glucose level. |  | 11 hours | 
| Mean plasma insulin concentration. |  | 11 hours | 
| Number of hypoglycemic events less than 3.3 mmol/L (>20 minutes). |  | 11 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, Closed-loop control, Artificial pancreas, Postprandial glucose control