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

This study has been completed.
Sponsor:
Collaborators:
Montreal Children's Hospital of the MUHC
Mount Sinai Hospital, New York
McGill University
Information provided by (Responsible Party):
Rémi Rabasa-Lhoret, Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier:
NCT01905020
First received: July 12, 2013
Last updated: October 18, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Other: Carbohydrate-rich meal
Other: Exercise
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Institut de Recherches Cliniques de Montreal:

Primary Outcome Measures:
  • Percentage of time in target range [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Percentage of time for which glucose levels are below 4.0 mmol/L.

  • Percentage of time spent below 3.3 mmol/L [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Area under the curve for glucose levels below 3.3 mmol/L [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Percentage of time spent above 8.0 mmol/L [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Percentage of time for which glucose levels are above 8.0 mmol/L

  • Percentage of time spent above 10.0 mmol/L [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Area under the curve for glucose levels spent above 10.0 mmol/L [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Mean glucose levels [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Standard deviation of glucose levels [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Standard deviation of glucose levels as a measure of glucose variability.

  • Total insulin delivery [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Number of subjects experiencing at least one hypoglycemic event requiring treatment [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
  • Number of hypoglycemic events requiring treatment [ Time Frame: 8 hours ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: July 2013
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01905020

Locations
Canada, Ontario
Mount Sinai Hospital
Toronto, Ontario, Canada
Canada, Quebec
Institut de recherches cliniques de Montréal
Montreal, Quebec, Canada
Montreal Children Hospital
Montreal, Quebec, Canada
Sponsors and Collaborators
Institut de Recherches Cliniques de Montreal
Montreal Children's Hospital of the MUHC
Mount Sinai Hospital, New York
McGill University
Investigators
Principal Investigator: Rémi Rabasa-Lhoret, MD, PhD Institut de recherches cliniques de Montréal
Principal Investigator: Bruce Perkins Mount Sinai Hospital, New York
  More Information

No publications provided

Responsible Party: Rémi Rabasa-Lhoret, Associate Professor of Medicine, Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier: NCT01905020     History of Changes
Other Study ID Numbers: CLASS-04
Study First Received: July 12, 2013
Last Updated: October 18, 2014
Health Authority: Canada: research ethic committee

Keywords provided by Institut de Recherches Cliniques de Montreal:
Type 1 diabetes
Hypoglycemia
Insulin
Glucagon
Closed-loop system
Artificial pancreas

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Hormones
Insulin
Insulin, Globin Zinc
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014