Clinical trial NCT01754337: Closed-loop Control of Glucose Levels (Artificial Pancreas) for 24 Hours in Adults and Adolescents With Type 1 Diabetes
Official title: 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 Pump Therapy in Regulating Glucose Levels During 24 Hours in Adults and Adolescents With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
Hypoglycemia
Insulin
Glucagon
Closed-loop system
Artificial pancreas
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
Collaborators: name: McGill University
name: Montreal Children's Hospital of the MUHC
First posted: 2012-12-21
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
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 system would regulate glucose levels through the infusion of two hormone: 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 pump therapy to regulate glucose levels in a 24-hours in-patient study with standardized conditions in adults and adolescents with type 1 diabetes.

The investigators hypothesized that dual-hormone closed-loop strategy is more effective in regulating glucose levels in adults and adolescents with type 1 diabetes compared to single-hormone closed-loop strategy, which in turn is more effective than the conventional pump therapy.

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 hormone: insulin and glucagon.

We aim to conduct the 1st randomized three-way cross-over trial comparing single hormone closed-loop strategy, dual-hormone closed-loop strategy and the conventional pump therapy. We aim to compare the three interventions for 24 hours in adults and adolescents with type 1 diabetes. Each 24 hours will include a 60-min exercise session, three meals characterizing a full day, activities that mimick real-life conditions and an overnight stay. This study will also allow for multiple comparisons and evaluating the benefits of each component separately (i.e. the benefits of merely closing the loop with insulin alone vs. adding glucagon to the closed-loop strategy).

Eligibility criteria: Inclusion Criteria:

1. Males and females ≥ 12 years of old.
2. Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
3. The subject will have been on insulin pump therapy for at least 3 months.
4. HbA1c ≤ 12%.

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. 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.
4. Pregnancy.
5. Severe hypoglycemic episode within two weeks of screening.
6. Current use of glucocorticoid medication (except low stable dose).
7. Known or suspected allergy to the trial products or meal contents.
8. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
9. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
10. Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc).

Primary outcomes:
measure: Percentage of time of plasma glucose levels spent in target range.
timeFrame: 24 hours
Secondary outcomes:
measure: Percentage of time of plasma glucose levels spent in the low range
timeFrame: 24 hours
measure: Percentage of overnight time of plasma glucose levels spent in the low range
timeFrame: 9 hours
measure: Standard deviation of glucose levels
timeFrame: 24 hours
measure: Total insulin delivery
timeFrame: 24 hours
measure: Mean plasma glucose level
timeFrame: 24 hours
measure: Mean plasma glucose level
timeFrame: 9 hours
measure: Mean plasma insulin concentration
timeFrame: 24 hours
measure: Mean plasma glucagon concentration
timeFrame: 24 hours
measure: Number of subjects experiencing hypoglycemia requiring oral treatment
timeFrame: 24 hours
measure: Percentage of time of plasma glucose levels spent between 4.0 and 10.0 mmol/L
timeFrame: 24 hours
measure: Percentage of overnight time of plasma glucose levels spent between 4.0 and 8.0 mmol/L
timeFrame: 9 hours
measure: Percentage of overnight time of plasma glucose levels spent between 4.0 and 10.0 mmol/L
timeFrame: 9 hours
measure: Percentage of time of plasma glucose levels spent in the high range
timeFrame: 24 hours
measure: Percentage of overnight time of plasma glucose levels spent in the high range
timeFrame: 9 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: Rémi Rabasa-Lhoret, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haidar A, Legault L, Messier V, Mitre TM, Leroux C, Rabasa-Lhoret R. Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial. Lancet Diabetes Endocrinol. 2015 Jan;3(1):17-26. doi: 10.1016/S2213-8587(14)70226-8. Epub 2014 Nov 27.