Closed-loop Control of Postprandial Glucose Levels After Meals With Different Macronutrients Content in Adults With Type 1 Diabetes

Study Overview
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Brief Summary
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Carbohydrates are the main determinant of post-meal glucose excursion. However, fat and protein have been shown to also impact the postprandial glucose control, adding to the complexity of meal insulin calculation. Few studies have looked at the effect of macronutrients other than carbohydrates on postprandial glucose excursions with the closed-loop strategy. The objective of this study is to test whether the single-hormone closed-loop strategy can achieve similar post-meal glucose control with meals with a fixed carbohydrate content, but high in protein and/or fat when compared to a meal with a fixed carbohydrate content only.

Official Title
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An Open-label, Randomized, Four-way, Cross-over Study to Examine the Efficacy of Single-hormone Closed-loop System in Regulating Glucose Levels in Adults With Type 1 Diabetes Following Meals of Various Macronutrient Contents: a Pilot Study

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Patient's insulin pump
* Drug: Insulin
* Device: Dexcom G4 Platinum glucose sensor
* Other: Single-hormone closed-loop


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years 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 and currently using fast-acting insulin analog (Lispro, Aspart or Guilisine). Last (less than 3 months) HbA1c ≤ 10%. 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 1 month of screening. Agents affecting gastric emptying (Motilium®, Prandase®, all GLP-1 analogs) as well as oral anti-diabetic agents (Metformin, SGLT-2 inhibitors and DPP-4 inhibitors) if not at a stable dose for 3 months. Otherwise, these medications are acceptable and will be kept stable during the entire protocol. Oral steroids unless patients present a low stable dose (e.g. 10 mg or less of prednisone per day or physiological doses, less than 35 mg/day, of hydrocortisone Cortef®). Inhaled steroids at stable dose in the last month are acceptable. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator (e.g. unstable psychiatric condition). Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).

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: Carbohydrate meal<br> | Device: Patient's insulin pump<br>* The patient's insulin pump will be used to regulate glucose levels.<br>Drug: Insulin<br>* Patient's usual fast-acting insulin analog will be used.<br>Device: Dexcom G4 Platinum glucose sensor<br>* The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.<br>Other: Single-hormone closed-loop<br>* Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.<br>|
| Active Comparator: Carbohydrate + fat meal<br> | Device: Patient's insulin pump<br>* The patient's insulin pump will be used to regulate glucose levels.<br>Drug: Insulin<br>* Patient's usual fast-acting insulin analog will be used.<br>Device: Dexcom G4 Platinum glucose sensor<br>* The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.<br>Other: Single-hormone closed-loop<br>* Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.<br>|
| Active Comparator: Carbohydrate + protein meal<br> | Device: Patient's insulin pump<br>* The patient's insulin pump will be used to regulate glucose levels.<br>Drug: Insulin<br>* Patient's usual fast-acting insulin analog will be used.<br>Device: Dexcom G4 Platinum glucose sensor<br>* The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.<br>Other: Single-hormone closed-loop<br>* Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.<br>|
| Active Comparator: Carbohydrate + fat + protein meal<br> | Device: Patient's insulin pump<br>* The patient's insulin pump will be used to regulate glucose levels.<br>Drug: Insulin<br>* Patient's usual fast-acting insulin analog will be used.<br>Device: Dexcom G4 Platinum glucose sensor<br>* The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.<br>Other: Single-hormone closed-loop<br>* Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of sensor glucose levels |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean sensor glucose levels |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Peak glucose excursion |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Time to peak glucose |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Percentage of time of sensor glucose concentrations between 3.9 and 7.8 mmol/L |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Percentage of time of sensor glucose concentrations between 3.9 and 10 mmol/L |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Percentage of time of sensor glucose concentrations above 10 mmol/L |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Percentage of time of sensor glucose concentrations above 13.9 mmol/L |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Total insulin delivery |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Standard deviation of glucose levels |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 
| Coefficient of variation of glucose levels |  | The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Closed-loop system, Artificial pancreas, Glucose control, Meal