Back to resultsClosed-loop Control of Overnight Glucose Levels in Adults and Adolescents With Type 1 Diabetes
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Carbohydrate-rich meal
Exercise
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 diabetes, Hypoglycemia, Insulin, Glucagon, Closed-loop system, Artificial pancreas
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.
Sites / Locations
- Mount Sinai Hospital
- Institut de recherches cliniques de Montréal
- Montreal Children Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Conventional insulin pump therapry
Single-hormone closed-loop system
Dual-hormone closed-loop system
Arm Description
Subjects will use conventional pump therapy to regulate their glucose levels.
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.
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.
Outcomes
Primary Outcome Measures
Percentage of time in target range
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
Percentage of time in target range for each night separately
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 in target range for the pooled data
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 below 4.0 mmol/L
Percentage of time for which glucose levels are below 4.0 mmol/L.
Percentage of time spent below 3.3 mmol/L
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
Area under the curve for glucose levels below 3.3 mmol/L
Percentage of time spent above 8.0 mmol/L
Percentage of time for which glucose levels are above 8.0 mmol/L
Percentage of time spent above 10.0 mmol/L
Percentage of time for which glucose levels are above 10.0 mmol/L.
Area under the curve for glucose levels spent above 8.0 mmol/L
Area under the curve for glucose levels spent above 10.0 mmol/L
Mean glucose levels
Standard deviation of glucose levels
Standard deviation of glucose levels as a measure of glucose variability.
Total insulin delivery
Number of subjects experiencing at least one hypoglycemic event requiring treatment
Number of hypoglycemic events requiring treatment
Full Information
NCT ID
NCT01905020
First Posted
July 12, 2013
Last Updated
October 18, 2014
Sponsor
Institut de Recherches Cliniques de Montreal
Collaborators
Montreal Children's Hospital of the MUHC, Mount Sinai Hospital, New York, McGill University
1. Study Identification
Unique Protocol Identification Number
NCT01905020
Brief Title
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
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherches Cliniques de Montreal
Collaborators
Montreal Children's Hospital of the MUHC, Mount Sinai Hospital, New York, McGill University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Type 1 diabetes, Hypoglycemia, Insulin, Glucagon, Closed-loop system, Artificial pancreas
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Conventional insulin pump therapry
Arm Type
Active Comparator
Arm Description
Subjects will use conventional pump therapy to regulate their glucose levels.
Arm Title
Single-hormone closed-loop system
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Dual-hormone closed-loop system
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Carbohydrate-rich meal
Intervention Description
At 19:30, patients will eat a standardized large meal (110g carbohydrate for males; 90g carbohydrate for females). Conventional insulin pump therapy or closed-loop system will be use to control glucose levels from 21:00 until 7:00 next morning.
Intervention Type
Other
Intervention Name(s)
Exercise
Intervention Description
Study participants will go to a training facility around 18:00 to perform a 60min workout at 60% heart rate reserve. The workout will be on a treadmill and/or a stationary bicycle. Conventional insulin pump therapy or closed-loop system will be use to regulate glucose levels from 21:00 until 7:00 next morning.
Primary Outcome Measure Information:
Title
Percentage of time in target range
Description
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
Time Frame
8 hours
Secondary Outcome Measure Information:
Title
Percentage of time in target range for each night separately
Description
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.
Time Frame
8 hours
Title
Percentage of time in target range for the pooled data
Description
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.
Time Frame
8 hours
Title
Percentage of time spent below 4.0 mmol/L
Description
Percentage of time for which glucose levels are below 4.0 mmol/L.
Time Frame
8 hours
Title
Percentage of time spent below 3.3 mmol/L
Description
Percentage of time for which glucose levels are spent below 3.3 mmol/L.
Time Frame
8 hours
Title
Area under the curve for glucose levels below 4.0 mmol/L
Time Frame
8 hours
Title
Area under the curve for glucose levels below 3.3 mmol/L
Time Frame
8 hours
Title
Percentage of time spent above 8.0 mmol/L
Description
Percentage of time for which glucose levels are above 8.0 mmol/L
Time Frame
8 hours
Title
Percentage of time spent above 10.0 mmol/L
Description
Percentage of time for which glucose levels are above 10.0 mmol/L.
Time Frame
8 hours
Title
Area under the curve for glucose levels spent above 8.0 mmol/L
Time Frame
8 hours
Title
Area under the curve for glucose levels spent above 10.0 mmol/L
Time Frame
8 hours
Title
Mean glucose levels
Time Frame
8 hours
Title
Standard deviation of glucose levels
Description
Standard deviation of glucose levels as a measure of glucose variability.
Time Frame
8 hours
Title
Total insulin delivery
Time Frame
8 hours
Title
Number of subjects experiencing at least one hypoglycemic event requiring treatment
Time Frame
8 hours
Title
Number of hypoglycemic events requiring treatment
Time Frame
8 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rémi Rabasa-Lhoret, MD, PhD
Organizational Affiliation
Institut de recherches cliniques de Montréal
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bruce Perkins
Organizational Affiliation
MOUNT SINAI HOSPITAL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Institut de recherches cliniques de Montréal
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Montreal Children Hospital
City
Montreal
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
26523526
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.
Results Reference
derived
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Closed-loop Control of Overnight Glucose Levels in Adults and Adolescents With Type 1 Diabetes
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