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Closed-loop Control of Postprandial Glucose Levels in Children and Adults With Type 1 Diabetes

Primary Purpose

Type 1 Diabetes

Status

Withdrawn

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

6-day intervention with sensor-augmented pump therapy

6-day intervention with single-hormone closed-loop strategy

6-day intervention with dual-hormone closed-loop strategy

Insulin

Glucagon

Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Insulin pump MiniMed® Paradigm® Veo™, Medtronic

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 diabetes, Closed-loop system, Artificial pancreas, Insulin, Glucagon, Hypoglycemia, Postprandial glucose

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males and females ≥ 8 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 a fast actin insulin analog (Lispro, Aspart or Guilisine).
Last (less than 3 months) HbA1c ≤ 10%.
Currently using carbohydrate counting as the meal insulin dose strategy.
Live in the area of Montreal

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.
Pregnancy.
Severe hypoglycemic episode within 1 month of screening.
Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) 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®). Inhale 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).
Living or planned travel outside Montreal (> 1h of driving) area during closed-loop procedures.

Sites / Locations

Institut de recherches cliniques de Montréal

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Arm Label

Single-hormone closed-loop strategy with full boluses

Dual-hormone closed-loop strategy with full boluses

Single-hormone closed-loop strategy with partial boluses

Dual-hormone closed-loop strategy with partial boluses

Sensor-augmented pump therapy

Arm Description

Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) 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 the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.

Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) and Glucagon (Eli Lilly) will be infused using two separate subcutaneous infusion pumps (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.

Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) 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 the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). For this strategy, meal size will be defined as: snack as any meal less than 30g, regular meal as any meal between 30g and 60g CHO, large meal as any meal between 60g and 90g CHO, very large meal for anything above 90g CHO. The meal size assessment will be done by the patient.

Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Guilisine) and Glucagon (Eli Lilly) will be infused using two separate subcutaneous infusion pumps (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). For this strategy, meal size will be defined as: snack as any meal less than 30g, regular meal as any meal between 30g and 60g CHO, large meal as any meal between 60g and 90g CHO, very large meal for anything above 90g CHO. The meal size assessment will be done by the patient.

Subjects will use sensor-augmented pump therapy and freely implement their usual basal rate and CHO-matching full prandial bolus to regulate glucose levels. Patient's usual fast acting insulin analog will be infused using a subcutaneous insulin infusion pump. Each subject insulin-to-carbohydrate ratio will be used to calculate the insulin bolus to be given.

Outcomes

Primary Outcome Measures

Mean day-and-night glucose levels

Secondary Outcome Measures

Percentage of time of glucose levels between 4.0 and 8.0 mmol/L

Percentage of time of glucose levels between 4.0 and 10.0 mmol/L

Percentage of time of glucose levels above 10.0 mmol/L

Percentage of time of glucose levels above 14.0 mmol/L

Percentage of time of glucose levels spent below 4.0 mmol/L

Percentage of time of glucose levels spent below 3.1 mmol/L

Area under the curve of glucose values below 4.0 mmol/L

Area under the curve of glucose values below 3.1 mmol/L

Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms

Total number of hypoglycemic event below 3.1 mmol/L

Total insulin delivery

Total glucagon delivery

Standard deviation of glucose levels

Total carbohydrate intake

Full Information

NCT ID

NCT02490098

First Posted

July 1, 2015

Last Updated

October 25, 2017

Sponsor

Institut de Recherches Cliniques de Montreal

Collaborators

Juvenile Diabetes Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT02490098

Brief Title

Closed-loop Control of Postprandial Glucose Levels in Children and Adults With Type 1 Diabetes

Official Title

An Open-label, Randomized, Five-way, Cross-over Study to Compare the Efficacy of Single- and Dual-hormone Closed-loop Operations Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation, and Sensor-augmented Pump Therapy in Regulating Glucose Levels in Children and Adults With Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Funding terminated

Study Start Date

January 2018 (Anticipated)

Primary Completion Date

July 2018 (Anticipated)

Study Completion Date

July 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institut de Recherches Cliniques de Montreal

Collaborators

Juvenile Diabetes Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Current intensive insulin therapy in T1D involves prandial insulin boluses depending on the carbohydrate content of each ingested meal. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Therefore, accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels in type 1 diabetes in order to avoid too much or too little insulin resulting in hypoglycemia and hyperglycemia, respectively. Precision of carbohydrate counting is associated with better glycemic control. However, accurate carbohydrate counting is a challenging task for many patients with type 1 diabetes. Recent developments of continuous glucose sensors and insulin infusion pumps have motivated the research toward "closed-loop'' strategies to regulate glucose levels in patients with type 1 diabetes. In a closed-loop strategy, the pump insulin infusion rate is altered based on a computer generated recommendation that rely on continuous glucose sensor readings. A dual-hormone closed-loop strategy has also been recently proposed to regulate glucose levels. In a dual-hormone strategy, subcutaneous insulin delivery is accompanied by subcutaneous glucagon infusion. Postprandial meal glucose control with closed-loop strategy still needs some improvements. The objective of this study is to test in outpatient unrestricted settings whether, in the context of closed-loop strategy, conventional meal carbohydrate counting could be reduced to a simplified qualitative meal size estimation without a significant degradation in overall glycemic control in children and adult patients with type 1 diabetes. The investigators hypothesize that 1) dual-hormone closed-loop strategy with qualitative meal size estimation is equivalent to dual-hormone closed-loop strategy with CHO counting in terms of mean glucose; 2) single-hormone closed-loop strategy with qualitative meal size estimation is equivalent to single-hormone closed-loop strategy with CHO counting in terms of mean glucose;

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

Keywords

Type 1 diabetes, Closed-loop system, Artificial pancreas, Insulin, Glucagon, Hypoglycemia, Postprandial glucose

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single-hormone closed-loop strategy with full boluses

Arm Type

Active Comparator

Arm Description

Arm Title

Dual-hormone closed-loop strategy with full boluses

Arm Type

Active Comparator

Arm Description

Arm Title

Single-hormone closed-loop strategy with partial boluses

Arm Type

Active Comparator

Arm Description

Variable subcutaneous insulin infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Glulisine) 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 the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). For this strategy, meal size will be defined as: snack as any meal less than 30g, regular meal as any meal between 30g and 60g CHO, large meal as any meal between 60g and 90g CHO, very large meal for anything above 90g CHO. The meal size assessment will be done by the patient.

Arm Title

Dual-hormone closed-loop strategy with partial boluses

Arm Type

Active Comparator

Arm Description

Variable subcutaneous insulin and glucagon infusion rates will be used to regulate postprandial glucose levels. Patient's usual fast acting insulin analog (Lispro, Aspart or Guilisine) and Glucagon (Eli Lilly) will be infused using two separate subcutaneous infusion pumps (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to the Smartphone platform, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. The partial bolus will be based on the estimated meal size (snack-regular-large-very large). For this strategy, meal size will be defined as: snack as any meal less than 30g, regular meal as any meal between 30g and 60g CHO, large meal as any meal between 60g and 90g CHO, very large meal for anything above 90g CHO. The meal size assessment will be done by the patient.

Arm Title

Sensor-augmented pump therapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

6-day intervention with sensor-augmented pump therapy

Intervention Description

One day prior to the intervention, participants will have to install a glucose sensor and the study insulin pump. Participants will adjust their insulin delivery as per their standard practice; including temporary basal and correction boluses. Participants will have access to their finger-stick glucose measurements and will be advised to measure their glucose level as per their standard practice. Participants will be asked to install a new infusion set every 2 days. Participants will be allowed to eat whatever they want and allowed to drink alcohol. Participants will use sensor-augmented pump therapy for 6 days.

Intervention Type

Other

Intervention Name(s)

6-day intervention with single-hormone closed-loop strategy

Intervention Description

One day prior to the intervention, participants will have to install a glucose sensor and the study insulin pump. On the first day of the intervention, participants will be admitted to the clinical research facility in the morning. A team member will review with the participant how to use study devices. 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 allowed to go home in the afternoon. They will be advised to continue with study intervention at home for the next 5 days. Participants will be asked to install a new infusion set every 2 days. Participants will be allowed to eat whatever they want and allowed to drink alcohol.

Intervention Type

Other

Intervention Name(s)

6-day intervention with dual-hormone closed-loop strategy

Intervention Description

One day prior to the intervention, participants will have to install a glucose sensor and the study insulin pump. On the first day of the intervention, participants will be admitted to the clinical research facility in the morning. Participants will have to install a second pump containing glucagon. A team member will review with the participant how to use study devices. 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 allowed to go home in the afternoon. They will be advised to continue with study intervention at home for the next 5 days. Participants will be asked to install a new infusion set every 2 days. Participants will be allowed to eat whatever they want and allowed to drink alcohol.

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Description

Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)

Intervention Type

Drug

Intervention Name(s)

Glucagon

Intervention Description

Glucagon (Eli Lilly) will be used during dual-hormone closed-loop strategy.

Intervention Type

Device

Intervention Name(s)

Continuous Glucose Monitoring System Enlite sensor®, Medtronic

Intervention Description

Enlite sensor®, Medtronic

Intervention Type

Device

Intervention Name(s)

Insulin pump MiniMed® Paradigm® Veo™, Medtronic

Intervention Description

MiniMed® Paradigm® Veo™, Medtronic

Primary Outcome Measure Information:

Title

Mean day-and-night glucose levels

Time Frame

6 days

Secondary Outcome Measure Information:

Title

Percentage of time of glucose levels between 4.0 and 8.0 mmol/L

Time Frame

6 days

Title

Percentage of time of glucose levels between 4.0 and 10.0 mmol/L

Time Frame

6 days

Title

Percentage of time of glucose levels above 10.0 mmol/L

Time Frame

6 days

Title

Percentage of time of glucose levels above 14.0 mmol/L

Time Frame

6 days

Title

Percentage of time of glucose levels spent below 4.0 mmol/L

Time Frame

6 days

Title

Percentage of time of glucose levels spent below 3.1 mmol/L

Time Frame

6 days

Title

Area under the curve of glucose values below 4.0 mmol/L

Time Frame

6 days

Title

Area under the curve of glucose values below 3.1 mmol/L

Time Frame

6 days

Title

Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms

Time Frame

6 days

Title

Total number of hypoglycemic event below 3.1 mmol/L

Time Frame

6 days

Title

Total insulin delivery

Time Frame

6 days

Title

Total glucagon delivery

Time Frame

6 days

Title

Standard deviation of glucose levels

Time Frame

6 days

Title

Total carbohydrate intake

Time Frame

6 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males and females ≥ 8 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 a fast actin insulin analog (Lispro, Aspart or Guilisine). Last (less than 3 months) HbA1c ≤ 10%. Currently using carbohydrate counting as the meal insulin dose strategy. Live in the area of Montreal 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. Pregnancy. Severe hypoglycemic episode within 1 month of screening. Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) 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®). Inhale 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). Living or planned travel outside Montreal (> 1h of driving) area during closed-loop procedures.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rémi Rabasa-Lhoret

Organizational Affiliation

Institut de recherches cliniques de Montréal

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut de recherches cliniques de Montréal

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2W 1R7

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

Closed-loop Control of Postprandial Glucose Levels in Children and Adults With Type 1 Diabetes

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