Closed-loop Control of Glucose Levels (Artificial Pancreas) During Exercise 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. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormones: insulin and glucagon. The objective is to compare the efficacy of single-hormone closed-loop strategy and dual-hormone closed-loop strategy at regulating glucose levels during continuous exercise and interval exercise. The investigator hypothesized that dual-hormone closed-loop strategy is superior to single-hormone closed-loop strategy in regulating glucose levels during exercise periods.

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 hormones: insulin and glucagon. We aim to conduct a randomized two-way cross-over trial comparing single-hormone closed-loop strategy and dual-hormone closed-loop strategy to compare the two interventions during exercise periods in adults with type 1 diabetes. A moderate intensity exercise will be performed for 60 minutes at 60% of the maximum oxygen consumption (VO2max). A high intensity exercise will be 40 minutes of interval training. The interval training will be preceded by a 10 minutes warm-up and followed by a 10 minutes cool down.

Official Title
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An Open-label, Randomized, Cross-over Study to Compare the Efficacy of Single-hormone Closed-loop Strategy and Dual-hormone Closed-loop Strategy at Regulating Glucose Levels During Continuous Exercise and Interval Exercise in Adults With Type-1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: 60-minute exercise
* Other: 40-minute interval exercise


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. Last (less than 3 months) HbA1c ≤ 12%. Exclusion Criteria: Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator. Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery. Ongoing pregnancy. Severe hypoglycemic episode within two weeks of screening. Other serious medical illness likely to interfere with study participation or with the ability to complete the exercise periods by the judgment of the investigator (e.g. orthopedic limitation). Failure to comply with team's recommendations (e.g. not willing to eat snack, 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single-hormone closed-loop system<br>In single-hormone closed-loop system, variable subcutaneous insulin infusion rate will be used to regulate glucose levels | Other: 60-minute exercise<br>* Patients will be admitted at the research clinical facility at 14:30. Closed-loop strategy will start at 15:30. At 18:00, patients will performed a 60-minute exercise at 60% of VO2 max. Patients will be discharged at 20:00.<br>Other: 40-minute interval exercise<br>* Patients will be admitted at the research clinical facility at 14:30. Closed-loop strategy will start at 15:30. At 18:00, patients will performed a 40-minute interval exercise. Patients will be discharged at 20:00.<br>|
| Active Comparator: Dual-hormone closed-loop system<br>In dual-hormone closed-loop system, variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels | Other: 60-minute exercise<br>* Patients will be admitted at the research clinical facility at 14:30. Closed-loop strategy will start at 15:30. At 18:00, patients will performed a 60-minute exercise at 60% of VO2 max. Patients will be discharged at 20:00.<br>Other: 40-minute interval exercise<br>* Patients will be admitted at the research clinical facility at 14:30. Closed-loop strategy will start at 15:30. At 18:00, patients will performed a 40-minute interval exercise. Patients will be discharged at 20:00.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients experiencing exercise-induced hypoglycemia requiring dextrose infusion (< 3.3 mmol/L symptomatic or < 3.0 mmol/L regardless of symptoms). |  | 18:00 hours to 19:30 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in glucose levels during each exercise | Difference between glucose levels at the beginning of the exercise and the lowest glucose level from the start of the exercise until 30 minutes after exercise). | 18:00 to 19:30 hours or 18:00 to 19:10 depending on the exercise performed | 
| Area under the curve of plasma glucose levels < 4 mmol/L |  | 15:30 hours to 19:30 hours | 
| Percentage of time of plasma glucose levels < 4 mmol/L |  | 15:30 hours to 19:30 hours | 
| Number of patients with an exercise-induced hypoglycemia < 3.9 mmol/L |  | 15:30 hours to 19:30 hours | 
| Decremental area under the curve from the start of the exercise for 90 minutes. |  | 18:00 to 19:30 | 
| Percentage of time-in-target defined as between 4 and 10 mmol/L |  | 15:30 hours to 19:30 hours | 
| Mean time (minutes) to the first hypoglycemic event during the exercise period |  | 18:00 to 19:00 | 
| The amount of dextrose infused |  | 15:30 to 19:30 | 

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