Closed-loop Control of Overnight Glucose Levels (Artificial Pancreas) in Type 1 Diabètes Adults With Hypoglycemia Unawareness and Documented Nocturnal Hypoglycemia

An Open-label, Randomized, Cross-over Study to Assess the Efficacy of Single-hormone and Dual-hormone Closed-loop Strategy in Regulating Overnight Glucose Levels in Type 1 diabètes Adults With Hypoglycemia Unawareness and Documented Nocturnal Hypoglycemia

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 and dual-hormone closed-loop strategy to regulate overnight glucose levels in a in-patient study in type 1 diabetes adults with hypoglycemia unawareness and documented nocturnal hypoglycemia.

The investigators hypothesized that dual-hormone closed-loop strategy is more effective in regulating overnight glucose levels compared to single-hormone closed-loop strategy.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Overnight intervention

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 strategy would regulate glucose levels through the infusion of two hormones: insulin and glucagon.

The investigators aim to conduct the 1st randomized cross-over trial comparing single- hormone and dual-hormone closed-loop strategy to regulate overnight glucose levels. The investigators aim to compare the two interventions for 10 hours in two subgroups of adults with type 1 diabètes. Patients from both subgroups will present documented nocturnal hypoglycemia. One subgroup will consist of patients with hypoglycemia unawareness while the other subgroup will consist of patients with hypoglycemia unawareness. This study will allow to determine if there is a greater benefit of a closed-loop strategy in a higher-risk hypoglycemia unaware group.

• Study Type: Interventional
• Enrollment (Actual): 35
• 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:

1. Males and females ≥ 18 years of old.
2. Clinical diagnosis of type 1 diabetes for at least one year.
3. The subject will have been on insulin pump therapy for at least 3 months.
4. HbA1c ≤ 12%.
5. Hypoglycemia awareness or unawareness assessed by a questionnaire.
6. Documented NH during the run-in period.

Exclusion Criteria:

1. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
2. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
3. Pregnancy.
4. Severe hypoglycemic episode within two weeks of screening.
5. Current use of glucocorticoid medication (except low stable dose).
6. Known or suspected allergy to the trial products or snack contents.
7. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
8. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
9. Failure to comply with team's recommendations (e.g. not willing to eat snacks, 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
Active Comparator: Single-hormone closed-loop strategy	Other: Overnight intervention; Subjects will be admitted at the research facility at 19:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. On dual-hormone closed-loop visits, glucagon will be reconstituted according to the manufacturer's instructions and a MiniMed® Paradigm® Veo™ pump containing the glucagon solution will be installed. At 20:30, a snack containing 20g of carbohydrate will be given. Closed-loop strategy will start at 20:00 until 7:00 next morning. A glucose sensor reading will be entered manually in a tablet every 10 minutes. The tablet will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses (glucagon recommendations will only be generated during the dual hormone closed-loop visits). Pumps' parameters will then be changed manually to implement the tablet generated recommendations.
Active Comparator: Dual-hormone closed-loop strategy	Other: Overnight intervention; Subjects will be admitted at the research facility at 19:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. On dual-hormone closed-loop visits, glucagon will be reconstituted according to the manufacturer's instructions and a MiniMed® Paradigm® Veo™ pump containing the glucagon solution will be installed. At 20:30, a snack containing 20g of carbohydrate will be given. Closed-loop strategy will start at 20:00 until 7:00 next morning. A glucose sensor reading will be entered manually in a tablet every 10 minutes. The tablet will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses (glucagon recommendations will only be generated during the dual hormone closed-loop visits). Pumps' parameters will then be changed manually to implement the tablet generated recommendations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of time of plasma glucose levels spent below 4 mmol/L	Up to 8 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Total insulin delivery	Up to 8 hours
Percentage of time of plasma glucose levels spent between 4 and 8 mmol/L	Up to 8 hours
Percentage of time of plasma glucose levels spent between 4 and 10 mmol/L	Up to 8 hours
Percentage of time of plasma glucose levels spent below 3.5 mmol/L	Up to 8 hours
Percentage of time of plasma glucose levels spent below 3.3. mmol/L	Up to 8 hours
Percentage of time of plasma glucose levels spent above 8 mmol/L	Up to 8 hours
Percentage of time of plasma glucose levels spent above 10 mmol/L	Up to 8 hours
Area under the curve of plasma glucose levels spent below 4 mmol/L	Up to 8 hours
Area under the curve of plasma glucose levels spent below 3.5 mmol/L	Up to 8 hours
Area under the curve of plasma glucose levels spent below 3.3 mmol/L	Up to 8 hours
Area under the curve of plasma glucose levels spent above 8 mmol/L	Up to 8 hours
Area under the curve of plasma glucose levels spent above 10 mmol/L	Up to 8 hours
Mean plasma glucose levels	Up to 8 hours
Standard deviation of plasma glucose levels	Up to 8 hours
Total glucagon delivery	Up to 8 hours
Number of subjects experiencing at least one hypoglycemic event requiring oral treatment	Up to 8 hours
Total number of hypoglycemic events requiring treatment	Up to 8 hours

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal

Publications and helpful links

General Publications

• Abitbol A, Rabasa-Lhoret R, Messier V, Legault L, Smaoui M, Cohen N, Haidar A. Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial. Diabetes Technol Ther. 2018 Mar;20(3):189-196. doi: 10.1089/dia.2017.0353. Epub 2018 Feb 2.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: October 19, 2014
• First Submitted That Met QC Criteria: October 31, 2014
• First Posted (Estimate): November 4, 2014

Study Record Updates

• Last Update Posted (Estimate): November 10, 2016
• Last Update Submitted That Met QC Criteria: November 8, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Insulin; Hypoglycemia; Type 1 diabetes; Glucagon; Nocturnal hypoglycemia; Artificial pancreas; Hypoglycemia unawareness; Closed-loop strategy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Consciousness Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Unconsciousness
• Other Study ID Numbers: CLASS-09