Closed-loop Control of Glucose Levels (Artificial Pancreas) for 60 Hours in Adults With Type 1 Diabetes

An Open-label, Randomized, Three-way, Cross-over Study to Assess the Efficacy of Single-hormone Closed-loop Strategy, Dual-hormone Closed-loop Strategy and Conventional Insulin Pump Therapy in Regulating Glucose Levels During 60 Hours in Free-living Conditions in Patients 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 strategy would regulate glucose levels through the infusion of two hormones: insulin and glucagon.

The main objective of this project is to compare the efficacy of single-hormone closed-loop strategy, dual-hormone closed-loop strategy and conventional insulin pump therapy to regulate glucose levels in a 60-hours in non-standardized conditions in adults with type 1 diabetes.

The investigators hypothesized that 1) Controlling glucose levels using single- or dual-hormone CLS is feasible in free-living conditions for long period of time (60 hours); 2) Dual-hormone CLS is superior to single-hormone CLS as assessed by reducing time spent in hypoglycemic range; 3) Both single-hormone and dual-hormone CLS are superior to conventional pump therapy.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: 60-hours intervention

• Study Type: Interventional
• Enrollment (Actual): 23
• 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.
• HbA1c ≤ 12%.

Exclusion Criteria:

• Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
• Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• History of pheochromocytoma or insulinoma (glucagon could induce an hormonal response of these tumors)
• Beta-blockers at high dose based on investigator's evaluation of dosage interference with glucagon (glucagon can modify effect of beta-blockers, mostly evident at very high doses)
• Chronic indometacin treatment (can prevent glucagon effect on liver thus its ability to raise glucose)
• Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding)
• Anticholinergic drug (risk of interaction)
• Pregnancy.
• Severe hypoglycemic episode within two weeks of screening.
• Current use of glucocorticoid medication (except low stable dose and inhaled steroids).
• Known or suspected allergy to the trial products or meal contents (gluten free menus will be available).
• 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. need for major revision of carbohydrate counting).
• 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 meals/snacks, not willing to change pump parameters, etc).
• Treatments that could interfere with glucagon

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dual-hormone closed-loop strategy; In dual-hormone closed-loop strategy, variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels	Other: 60-hours intervention; Interventions will be conducted at the research centre (RC) or at the patient's home based on the patient's preference. If the study takes place at the RC, patients will be admitted at 7:00. If the study takes place at the patient's home, a research team member will be at the patient's home at 7:00. Closed-loop strategy will start at 8:00 on day 1 and end at 20:00 on day 3. During the interventions conducted at the RC, patients will have access to entertainment activities such as movies, video games, board games, foosball, etc. During the interventions conducted at the patient's home, patients will do their usual activities. For interventions conducted at the RC, patients will freely choose their meals from a large choice of prepared frozen meals. For interventions conducted at the patient's home, patients will freely choose their meals. Participants will be encouraged to conduct their usual physical activities whether they conduct the study at the RC or at the patient's home.
Active Comparator: Single-hormone closed-loop strategy; In single-hormone closed-loop strategy, variable subcutaneous insulin infusion rate will be used to regulate glucose levels	Other: 60-hours intervention; Interventions will be conducted at the research centre (RC) or at the patient's home based on the patient's preference. If the study takes place at the RC, patients will be admitted at 7:00. If the study takes place at the patient's home, a research team member will be at the patient's home at 7:00. Closed-loop strategy will start at 8:00 on day 1 and end at 20:00 on day 3. During the interventions conducted at the RC, patients will have access to entertainment activities such as movies, video games, board games, foosball, etc. During the interventions conducted at the patient's home, patients will do their usual activities. For interventions conducted at the RC, patients will freely choose their meals from a large choice of prepared frozen meals. For interventions conducted at the patient's home, patients will freely choose their meals. Participants will be encouraged to conduct their usual physical activities whether they conduct the study at the RC or at the patient's home.
Active Comparator: Conventional insulin pump therapy; In control visit, subjects will use conventional pump therapy to regulate glucose levels.	Other: 60-hours intervention; Interventions will be conducted at the research centre (RC) or at the patient's home based on the patient's preference. If the study takes place at the RC, patients will be admitted at 7:00. If the study takes place at the patient's home, a research team member will be at the patient's home at 7:00. Closed-loop strategy will start at 8:00 on day 1 and end at 20:00 on day 3. During the interventions conducted at the RC, patients will have access to entertainment activities such as movies, video games, board games, foosball, etc. During the interventions conducted at the patient's home, patients will do their usual activities. For interventions conducted at the RC, patients will freely choose their meals from a large choice of prepared frozen meals. For interventions conducted at the patient's home, patients will freely choose their meals. Participants will be encouraged to conduct their usual physical activities whether they conduct the study at the RC or at the patient's home.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time of glucose levels (as measured by continuous glucose sensor) spent in the hypoglycemic range.	Hypoglycemic range is defined to be between below 4 mmol/L	60 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time of glucose levels (as measured by continuous glucose sensor) spent in target range.	Target range is defined to be between 4 and 10 mmol/L from 7:00 to 22:00 and between 4 and 8 mmol/L from 22:00 to 7:00.	60 hours
Percentage of time of glucose levels spent below 3.5 mmol/L		60 hours
Percentage of time of glucose levels spent below 3.3 mmol/L		60 hours
Area under the curve of glucose values below 4.0 mmol/L		60 hours
Area under the curve of glucose values below 3.5 mmol/L		60 hours
Area under the curve of glucose values below 3.3 mmol/L		60 hours
Percentage of time of glucose levels spent above 8.0 mmol/L		60 hours
Percentage of time of glucose levels spent above 10.0 mmol/L		60 hours
Mean value of glucose levels		60 hours
Standard deviation of glucose levels		60 hours
Total insulin delivery		60 hours
Number of patients with at least one hypoglycemic event with or without symptoms below 3.0 mmol/L based on glucose sensor reading		60 hours

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal

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: October 17, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 21, 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 strategy
• 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-07