Clinical trial NCT01905020: Closed-loop Control of Overnight Glucose Levels in Adults and Adolescents With Type 1 Diabetes
Official title: An Open-label, Randomized, Three-way, Multicenter Study to Compare the Efficacy of Single-hormone Closed-loop Strategy, Dual-hormone Closed-loop Strategy and Conventional Insulin Pump Therapy in Regulating Overnight Glucose Levels at Home in Adolescents and Adults 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: Montreal Children's Hospital of the MUHC
name: Mount Sinai Hospital, New York
name: McGill University
First posted: 2013-07-22
Enrollment: 28
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 overnight glucose levels in a out-patient study in adults and adolescents with type 1 diabetes.

The investigators hypothesized that dual-hormone closed-loop strategy is more effective in regulating overnight 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 a multicenter study to compare the efficacy of conventional pump therapy, single-hormone closed-loop strategy and dual-hormone closed-loop strategy to regulate overnight glucose levels, at home, in adolescents and adults with type 1 diabetes. Each intervention will be tested on two nights: 1) After a carbohydrate-rich dinner meal (to exaggerate hyperglycemic risk and; 2) After an evening exercise (to exaggerate hypoglycemic risk).

Eligibility criteria: Inclusion Criteria:

* Males and females aged ≥ 12 years of old.
* Body mass index \< 35
* Clinical diagnosis of type 1 diabetes for at least one year.
* The subject will have been on insulin pump therapy for at least 4 months.
* HbA1c \< 12%.
* At least two visits with an endocrinology team in the past 1 year.

Exclusion Criteria:

* Clinically significant nephropathy, neuropathy (peripheral or autonomic e.g. significant gastroparesis) or retinopathy as judged by the investigator.
* 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.
* Ongoing pregnancy.
* Severe hypoglycemic episode within two weeks of screening.
* Current use of glucocorticoid medication (except low stable dose and inhaled therapy).
* Known or suspected allergy to the insulin aspart, glucagon, Medtronic sensors, or Medtronic infusion sets..
* 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 treatment regimen between admissions (such as a major change in an exercise routine, significant change in dietary routine or in insulin therapy.
* Failure to comply with team's recommendations.

Primary outcomes:
measure: Percentage of time in target range
timeFrame: 8 hours
Secondary outcomes:
measure: Percentage of time in target range for each night separately
timeFrame: 8 hours
measure: Percentage of time in target range for the pooled data
timeFrame: 8 hours
measure: Percentage of time spent below 4.0 mmol/L
timeFrame: 8 hours
measure: Percentage of time spent below 3.3 mmol/L
timeFrame: 8 hours
measure: Area under the curve for glucose levels below 4.0 mmol/L
timeFrame: 8 hours
measure: Area under the curve for glucose levels below 3.3 mmol/L
timeFrame: 8 hours
measure: Percentage of time spent above 8.0 mmol/L
timeFrame: 8 hours
measure: Percentage of time spent above 10.0 mmol/L
timeFrame: 8 hours
measure: Area under the curve for glucose levels spent above 8.0 mmol/L
timeFrame: 8 hours
measure: Area under the curve for glucose levels spent above 10.0 mmol/L
timeFrame: 8 hours
measure: Mean glucose levels
timeFrame: 8 hours
measure: Standard deviation of glucose levels
timeFrame: 8 hours
measure: Total insulin delivery
timeFrame: 8 hours
measure: Number of subjects experiencing at least one hypoglycemic event requiring treatment
timeFrame: 8 hours
measure: Number of hypoglycemic events requiring treatment
timeFrame: 8 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
city: Montreal
country: Canada
facility: Montreal Children Hospital
state: Quebec
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MOUNT SINAI HOSPITAL
name: Bruce Perkins
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haidar A, Rabasa-Lhoret R, Legault L, Lovblom LE, Rakheja R, Messier V, D'Aoust E, Falappa CM, Justice T, Orszag A, Tschirhart H, Dallaire M, Ladouceur M, Perkins BA. Single- and Dual-Hormone Artificial Pancreas for Overnight Glucose Control in Type 1 Diabetes. J Clin Endocrinol Metab. 2016 Jan;101(1):214-23. doi: 10.1210/jc.2015-3003. Epub 2015 Nov 2.