Closed-loop Control of Glucose Levels (Artificial Pancreas) During Exercise in Adults With Type 1 Diabetes

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: 60-minute exercise; Other: 40-minute interval exercise

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Institut de recherches cliniques de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single-hormone closed-loop system; In single-hormone closed-loop system, variable subcutaneous insulin infusion rate will be used to regulate glucose levels	Other: 60-minute exercise; 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.; Other: 40-minute interval exercise; 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.
Active Comparator: Dual-hormone closed-loop system; In dual-hormone closed-loop system, variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels	Other: 60-minute exercise; 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.; Other: 40-minute interval exercise; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: Société Francophone du Diabète

Publications and helpful links

General Publications

• Taleb N, Emami A, Suppere C, Messier V, Legault L, Ladouceur M, Chiasson JL, Haidar A, Rabasa-Lhoret R. Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial. Diabetologia. 2016 Dec;59(12):2561-2571. doi: 10.1007/s00125-016-4107-0. Epub 2016 Oct 4.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 23, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 28, 2013

Study Record Updates

• Last Update Posted (Estimate): May 4, 2015
• Last Update Submitted That Met QC Criteria: May 1, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Insulin; Hypoglycemia; Type 1 diabetes; Glucagon; Artificial pancreas; Closed-loop system
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CLASS-06