Clinical trial NCT02282254: Closed-loop Control of Overnight Glucose Levels (Artificial Pancreas) in Type 1 Diabètes Adults With Hypoglycemia Unawareness and Documented Nocturnal Hypoglycemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
Hypoglycemia unawareness
Nocturnal hypoglycemia
Closed-loop strategy
Artificial pancreas
Glucagon
Hypoglycemia
Insulin
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
First posted: 2014-11-04
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of time of plasma glucose levels spent below 4 mmol/L
timeFrame: Up to 8 hours
Secondary outcomes:
measure: Percentage of time of plasma glucose levels spent between 4 and 8 mmol/L
timeFrame: Up to 8 hours
measure: Percentage of time of plasma glucose levels spent between 4 and 10 mmol/L
timeFrame: Up to 8 hours
measure: Percentage of time of plasma glucose levels spent below 3.5 mmol/L
timeFrame: Up to 8 hours
measure: Percentage of time of plasma glucose levels spent below 3.3. mmol/L
timeFrame: Up to 8 hours
measure: Percentage of time of plasma glucose levels spent above 8 mmol/L
timeFrame: Up to 8 hours
measure: Percentage of time of plasma glucose levels spent above 10 mmol/L
timeFrame: Up to 8 hours
measure: Area under the curve of plasma glucose levels spent below 4 mmol/L
timeFrame: Up to 8 hours
measure: Area under the curve of plasma glucose levels spent below 3.5 mmol/L
timeFrame: Up to 8 hours
measure: Area under the curve of plasma glucose levels spent below 3.3 mmol/L
timeFrame: Up to 8 hours
measure: Area under the curve of plasma glucose levels spent above 8 mmol/L
timeFrame: Up to 8 hours
measure: Area under the curve of plasma glucose levels spent above 10 mmol/L
timeFrame: Up to 8 hours
measure: Mean plasma glucose levels
timeFrame: Up to 8 hours
measure: Standard deviation of plasma glucose levels
timeFrame: Up to 8 hours
measure: Total insulin delivery
timeFrame: Up to 8 hours
measure: Total glucagon delivery
timeFrame: Up to 8 hours
measure: Number of subjects experiencing at least one hypoglycemic event requiring oral treatment
timeFrame: Up to 8 hours
measure: Total number of hypoglycemic events requiring treatment
timeFrame: Up to 8 hours
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Remi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.