Closed-loop Control of Glucose Levels in the Context of Exercise in Adults With Type-1 Diabetes (CLASS-01)

An Open-label, Randomized, Two-way, Cross-over Study to Assess the Efficacy of Dual-hormone Closed-loop Strategy as Compared to Conventional CSII Therapy in Regulating Glucose Levels in Adults With Type-1 Diabetes in the Context of Exercise

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(s) infusion rate is altered based on a computer-generated recommendation that relies on continuous glucose sensor readings. In this study, we aim to compare the effectiveness of dual-hormone (insulin+glucagon) closed-loop strategy to open-loop conventional continuous subcutaneous insulin infusion pump (CSII) therapy in regulating glucose levels during an evening exercise and on a night following an exercise in adults with type 1 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Conventional continuous subcutaneous insulin infusion therapy; Device: Dual-hormone closed-loop

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Institut de recherches cliniques de Montréal (IRCM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of type 1 diabetes for at least one year.
• On insulin pump therapy for at least 3 months.
• HbA1c ≤ 10%.

Exclusion Criteria:

• Clinically significant nephropathy, neuropathy or retinopathy.
• Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• A recent injury to body or limb, muscular disorder, use of any medication or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the exercise protocol.
• Pregnancy.
• Severe hypoglycemic episode within two weeks of screening.
• Current use of glucocorticoid medication (by any route of administration except low dose stable inhaled).
• 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.
• Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
• Failure to comply with team's recommendations (e.g. not willing to eat snack, not willing to change pump parameters, etc).

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
Placebo Comparator: Open-loop; Conventional continuous subcutaneous insulin infusion (CSII) therapy	Device: Conventional continuous subcutaneous insulin infusion therapy
Experimental: Dual-hormone closed-loop; Variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels. The infusion rates are based on continuous glucose sensor reading and a control algorithm.	Device: Dual-hormone closed-loop

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of time of plasma glucose concentrations spent in target range (4.0-10.0 mmol/l from 4:00p.m.-11:00p.m. and 4.0-8.0 mmol/l from 11:00p.m.-7:00a.m.)	4 p.m. - 7 a.m.

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of time of plasma glucose concentrations spent in the low range (< 4.0 mmol/l).	4 p.m. - 7 a.m.
Percentage of time of plasma glucose concentrations spent in the high range (>10.0 mmol/l from 4:00p.m.-11:00 p.m. and >8.0 mmol/l from 11:00 p.m.-7:00 a.m.).	4 p.m. - 7 a.m
Percentage of overnight time of plasma glucose concentrations spent in target range (4.0 - 8.0 mmol/l).	11 p.m. - 7 a.m.
Percentage of overnight time of plasma glucose concentrations spent in the low range ( < 4.0 mmol/l).	11 p.m. - 7 a.m.
Percentage of overnight time of plasma glucose concentrations spent in the high range (above 8 mmol/l).	11 p.m. - 7 a.m.
Total insulin delivery.	4 p.m. - 7 a.m.
Total overnight insulin delivery (11 p.m. - 7 a.m.).	11 p.m. - 7 a.m.
Standard deviation and/or MAGE (Mean Amplitude of Glycemic Excursions) index of plasma glucose concentrations as measures of glucose variability.	4 p.m. - 7 a.m.
Number of subjects with at least one plasma glucose measurement less than 3.9 mmol/l.	4 p.m. - 7 a.m.
Number of subjects with at least one overnight plasma glucose measurement less than 3.9 mmol/l.	11 p.m. - 7 a.m
Number of subjects with at least one exercise-induced plasma glucose measurement less than 3.9 mmol/l.	5:50 p.m. - 7:20 p.m
Number of subjects with as at least one plasma glucose measurement below 3.3 mmol/l.	4 p.m. - 7 a.m.
Number of subjects with at least one overnight plasma glucose measurement below 3.3 mmol/l.	11 p.m. - 7 a.m
Number of subjects with at least one exercise-induced plasma glucose measurement below 3.3 mmol/l.	5:50 p.m. - 7:20 p.m
Number of subjects with as at least one plasma glucose measurement below 3.0 mmol/l.	4 p.m. - 7 a.m.
Number of subjects with at least one overnight plasma glucose measurement below 3.0 mmol/l.	11 p.m. - 7 a.m
Number of subjects with at least one exercise-induced plasma glucose measurement below 3.0 mmol/l.	5:50 p.m. - 7:20 p.m

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: McGill University; Montreal Children's Hospital of the MUHC; Diabetes Québec; Medtronic Minimed
• Investigators: Principal Investigator: Rémi Rabasa-Lhoret, M.D., Ph.D., Institut de recherches cliniques de Montréal (IRCM)

Publications and helpful links

General Publications

• Heyland DK, Heyland R, Bailey A, Howard M. A novel decision aid to help plan for serious illness: a multisite randomized trial. CMAJ Open. 2020 Apr 28;8(2):E289-E296. doi: 10.9778/cmajo.20190179. Print 2020 Apr-Jun.
• Haidar A, Legault L, Dallaire M, Alkhateeb A, Coriati A, Messier V, Cheng P, Millette M, Boulet B, Rabasa-Lhoret R. Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial. CMAJ. 2013 Mar 5;185(4):297-305. doi: 10.1503/cmaj.121265. Epub 2013 Jan 28.

Study record dates

Study Registration Dates

• First Submitted: February 15, 2011
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (Estimate): February 17, 2011

Study Record Updates

• Last Update Posted (Estimate): April 23, 2012
• Last Update Submitted That Met QC Criteria: April 20, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: CLASS-01