Closed-loop Control of Glucose Levels (Artificial Pancreas) for 24 Hours in Adults and Adolescents With Type 1 Diabetes

This study has been completed.
Sponsor:
Collaborators:
McGill University
Montreal Children's Hospital of the MUHC
Information provided by (Responsible Party):
Rémi Rabasa-Lhoret, Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier:
NCT01754337
First received: December 13, 2012
Last updated: July 3, 2014
Last verified: July 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 glucose levels in a 24-hours in-patient study with standardized conditions in adults and adolescents with type 1 diabetes.

The investigators hypothesized that dual-hormone closed-loop strategy is more effective in regulating 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: Closed-loop system
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, Cross-over Study to Assess the Efficacy of Single-hormone Closed-loop Strategy, Dual-hormone Closed-loop Strategy and Conventional Pump Therapy in Regulating Glucose Levels During 24 Hours in Adults and Adolescents 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 of plasma glucose levels spent in target range. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Two-hour postprandial target range is between 4.0 and 10.0 mmol/l. Otherwise, target range is defined to be between 4.0 and 8.0 mmol/l.


Secondary Outcome Measures:
  • Percentage of time of plasma glucose levels spent in the low range [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Low range is defined to be a. below 4 mmol/L; b. below 3.5 mmol/L; c. below 3.3 mmol/L.

  • Percentage of overnight time of plasma glucose levels spent in the low range [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
    Low range is defined to be a. < 4 mmol/L; b. < 3.5 mmol/L; c. < 3.3 mmol/L.

  • Standard deviation of glucose levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Measure of glucose variability

  • Total insulin delivery [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Mean plasma glucose level [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Mean plasma glucose level [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
  • Mean plasma insulin concentration [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Mean plasma glucagon concentration [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Number of subjects experiencing hypoglycemia requiring oral treatment [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Number of subjects experiencing hypoglycemia requiring oral treatment during a. the overall study period; b. the exercise; c. the night.

  • Percentage of time of plasma glucose levels spent between 4.0 and 10.0 mmol/L [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Percentage of overnight time of plasma glucose levels spent between 4.0 and 8.0 mmol/L [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
  • Percentage of overnight time of plasma glucose levels spent between 4.0 and 10.0 mmol/L [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
  • Percentage of time of plasma glucose levels spent in the high range [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    High range is defined to be above a. 8.0 mmol/L; b. 10.0 mmol/L

  • Percentage of overnight time of plasma glucose levels spent in the high range [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
    High range is defined to be above a. 8.0 mmol/L; b. 10.0 mmol/L.


Estimated Enrollment: 30
Study Start Date: December 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Single-hormone closed-loop system
In single-hormone closed-loop system, variable subcutaneous insulin infusion rate will be used to regulate glucose levels.
Other: Closed-loop system
Patients will be admitted at the research clinical facility at 7:00. At 8:00, a mixed meal will be served. At 9:00, patients will be asked to perform two 30-min standardized activities. At 12:00, a mixed meal will be served. At 13:00, patients will be asked to perform two 30-min activities. At 17:00, a mixed meal will be served. At 19:30, patients will perform 60 minutes of aerobic treadmill exercise at an intensity of 60% VO2max. A bedtime snack of 20g carbohydrate will be given at 21:00. Patients will be discharged at 8:00 the next morning
Active Comparator: Dual-hormone closed-loop system
In dual-hormone closed-loop system, variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels.
Other: Closed-loop system
Patients will be admitted at the research clinical facility at 7:00. At 8:00, a mixed meal will be served. At 9:00, patients will be asked to perform two 30-min standardized activities. At 12:00, a mixed meal will be served. At 13:00, patients will be asked to perform two 30-min activities. At 17:00, a mixed meal will be served. At 19:30, patients will perform 60 minutes of aerobic treadmill exercise at an intensity of 60% VO2max. A bedtime snack of 20g carbohydrate will be given at 21:00. Patients will be discharged at 8:00 the next morning
Active Comparator: Insulin pump therapy
Patient's conventional treatment will be implemented.
Other: Closed-loop system
Patients will be admitted at the research clinical facility at 7:00. At 8:00, a mixed meal will be served. At 9:00, patients will be asked to perform two 30-min standardized activities. At 12:00, a mixed meal will be served. At 13:00, patients will be asked to perform two 30-min activities. At 17:00, a mixed meal will be served. At 19:30, patients will perform 60 minutes of aerobic treadmill exercise at an intensity of 60% VO2max. A bedtime snack of 20g carbohydrate will be given at 21:00. Patients will be discharged at 8:00 the 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 the 1st randomized three-way cross-over trial comparing single hormone closed-loop strategy, dual-hormone closed-loop strategy and the conventional pump therapy. We aim to compare the three interventions for 24 hours in adults and adolescents with type 1 diabetes. Each 24 hours will include a 60-min exercise session, three meals characterizing a full day, activities that mimick real-life conditions and an overnight stay. This study will also allow for multiple comparisons and evaluating the benefits of each component separately (i.e. the benefits of merely closing the loop with insulin alone vs. adding glucagon to the closed-loop strategy).

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females ≥ 12 years of old.
  2. Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
  3. The subject will have been on insulin pump therapy for at least 3 months.
  4. HbA1c ≤ 12%.

Exclusion Criteria:

  1. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
  2. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
  3. 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.
  4. Pregnancy.
  5. Severe hypoglycemic episode within two weeks of screening.
  6. Current use of glucocorticoid medication (except low stable dose).
  7. Known or suspected allergy to the trial products or meal contents.
  8. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
  9. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
  10. Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc).
  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: NCT01754337

Locations
Canada, Quebec
Institut de recherches cliniques de Montréal
Montreal, Quebec, Canada, H2W 1R7
Sponsors and Collaborators
Institut de Recherches Cliniques de Montreal
McGill University
Montreal Children's Hospital of the MUHC
Investigators
Principal Investigator: Rémi Rabasa-Lhoret, MD, PhD Institut de recherches cliniques de Montréal
  More Information

No publications provided

Responsible Party: Rémi Rabasa-Lhoret, Associate professor of Medicine, Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier: NCT01754337     History of Changes
Other Study ID Numbers: CLASS-03
Study First Received: December 13, 2012
Last Updated: July 3, 2014
Health Authority: Canada: Ethics Review 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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014