Closed-loop Control of Overnight Glucose Levels in Adults and Adolescents With Type 1 Diabetes

Phase 2

Completed

Conditions: Type 1 Diabetes

Interventions: Other: Carbohydrate-rich meal
Other: Exercise

Registration Number: NCT01905020

Lead Sponsor: Institut de Recherches Cliniques de Montreal

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Single-hormone closed-loop system	Carbohydrate-rich meal	Variable subcutaneous insulin infusion rate will be used to regulate glucose levels. Insulin Aspart (Novorapid) will be infused using a subcutaneous infusion pump. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The pump's infusion rate will then be changed manually based on the computer-generated recommendations of infusion rates.
Dual-hormone closed-loop system	Carbohydrate-rich meal	Insulin Aspart (Novorapid) and glucagon (Paladin) will be infused using two separate subcutaneous infusion pumps. The glucose levels as measured by the real time sensor will be entered manually into the computer every 10 minutes. The pumps' infusion rate will then be changed manually based on the computer generated-recommendation delivery levels.
Conventional insulin pump therapry	Exercise	Subjects will use conventional pump therapy to regulate their glucose levels.
Single-hormone closed-loop system	Exercise	Variable subcutaneous insulin infusion rate will be used to regulate glucose levels. Insulin Aspart (Novorapid) will be infused using a subcutaneous infusion pump. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The pump's infusion rate will then be changed manually based on the computer-generated recommendations of infusion rates.
Dual-hormone closed-loop system	Exercise	Insulin Aspart (Novorapid) and glucagon (Paladin) will be infused using two separate subcutaneous infusion pumps. The glucose levels as measured by the real time sensor will be entered manually into the computer every 10 minutes. The pumps' infusion rate will then be changed manually based on the computer generated-recommendation delivery levels.
Conventional insulin pump therapry	Carbohydrate-rich meal	Subjects will use conventional pump therapy to regulate their glucose levels.

Primary Outcome Measures

Name	Time	Method
Percentage of time in target range	8 hours	Percentage of time for which glucose levels (as measured by the glucose sensor) are in target range. Target range is defined to be between 4.0 to 8.0 mmol/L

Secondary Outcome Measures

Name	Time	Method
Percentage of time spent above 8.0 mmol/L	8 hours	Percentage of time for which glucose levels are above 8.0 mmol/L
Percentage of time in target range for the pooled data	8 hours	Percentage of time for which glucose levels are in target range for the pooled data. Target range is defined to be between 4.0 to 8.0 mmol/L.
Percentage of time spent above 10.0 mmol/L	8 hours	Percentage of time for which glucose levels are above 10.0 mmol/L.
Number of subjects experiencing at least one hypoglycemic event requiring treatment	8 hours
Percentage of time spent below 4.0 mmol/L	8 hours	Percentage of time for which glucose levels are below 4.0 mmol/L.
Area under the curve for glucose levels below 3.3 mmol/L	8 hours
Percentage of time in target range for each night separately	8 hours	Percentage of time for which glucose levels are in target range for each night separately. Target range is defined to be between 4.0 and 8.0 mmol/L.
Percentage of time spent below 3.3 mmol/L	8 hours	Percentage of time for which glucose levels are spent below 3.3 mmol/L.
Area under the curve for glucose levels below 4.0 mmol/L	8 hours
Area under the curve for glucose levels spent above 8.0 mmol/L	8 hours
Mean glucose levels	8 hours
Standard deviation of glucose levels	8 hours	Standard deviation of glucose levels as a measure of glucose variability.
Area under the curve for glucose levels spent above 10.0 mmol/L	8 hours
Number of hypoglycemic events requiring treatment	8 hours
Total insulin delivery	8 hours

Trial Locations

Locations (3): Institut de recherches cliniques de Montréal
🇨🇦
Montreal, Quebec, Canada
Montreal Children Hospital
🇨🇦
Montreal, Quebec, Canada
Mount Sinai Hospital
🇨🇦
Toronto, Ontario, Canada