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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Carbohydrate-rich meal; Other: Exercise

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).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Institut de Recherches Cliniques de Montreal
    • Montreal, Quebec, Canada
      • Montreal Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional insulin pump therapry; Subjects will use conventional pump therapy to regulate their glucose levels.	Other: Carbohydrate-rich meal; 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.; Other: Exercise; 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.
Active Comparator: Single-hormone closed-loop system; 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.	Other: Carbohydrate-rich meal; 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.; Other: Exercise; 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.
Active Comparator: Dual-hormone closed-loop system; 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.	Other: Carbohydrate-rich meal; 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.; Other: Exercise; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 hours
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.	8 hours
Percentage of time spent below 4.0 mmol/L	Percentage of time for which glucose levels are below 4.0 mmol/L.	8 hours
Percentage of time spent below 3.3 mmol/L	Percentage of time for which glucose levels are spent below 3.3 mmol/L.	8 hours
Area under the curve for glucose levels below 4.0 mmol/L		8 hours
Area under the curve for glucose levels below 3.3 mmol/L		8 hours
Percentage of time spent above 8.0 mmol/L	Percentage of time for which glucose levels are above 8.0 mmol/L	8 hours
Percentage of time spent above 10.0 mmol/L	Percentage of time for which glucose levels are above 10.0 mmol/L.	8 hours
Area under the curve for glucose levels spent above 8.0 mmol/L		8 hours
Area under the curve for glucose levels spent above 10.0 mmol/L		8 hours
Mean glucose levels		8 hours
Standard deviation of glucose levels	Standard deviation of glucose levels as a measure of glucose variability.	8 hours
Total insulin delivery		8 hours
Number of subjects experiencing at least one hypoglycemic event requiring treatment		8 hours
Number of hypoglycemic events requiring treatment		8 hours

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: McGill University; Mount Sinai Hospital, New York; Montreal Children's Hospital of the MUHC
• Investigators: Principal Investigator: Bruce Perkins, Mount Sinai Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 12, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Estimate): October 21, 2014
• Last Update Submitted That Met QC Criteria: October 18, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Insulin; Hypoglycemia; Type 1 diabetes; Glucagon; Artificial pancreas; Closed-loop system
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CLASS-04