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

NCT01905020 | Completed Phase 2

• 1 other identifier: CLASS-04
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Hypoglycemia; Insulin; Glucagon; Closed-loop system; Artificial pancreas

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Percentage of time in target range for each night separately

  8 hours

• Percentage of time in target range for the pooled data

  8 hours

• Percentage of time spent below 4.0 mmol/L

  8 hours

• Percentage of time spent below 3.3 mmol/L

  8 hours

• Area under the curve for glucose levels below 4.0 mmol/L

  8 hours

Study Arms (3)

Conventional insulin pump therapry

ACTIVE COMPARATOR

Subjects will use conventional pump therapy to regulate their glucose levels.

Other: Carbohydrate-rich meal; Other: Exercise

Single-hormone closed-loop system

ACTIVE COMPARATOR

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; Other: Exercise

Dual-hormone closed-loop system

ACTIVE COMPARATOR

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; Other: Exercise

Interventions

Carbohydrate-rich meal OTHER

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.

Conventional insulin pump therapry; Dual-hormone closed-loop system; Single-hormone closed-loop system

Exercise OTHER

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.

Conventional insulin pump therapry; Dual-hormone closed-loop system; Single-hormone closed-loop system

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Cliniques de Montreal: lead
• Montreal Children's Hospital of the MUHC: collaborator
• Mount Sinai Hospital, New York: collaborator
• McGill University: collaborator

Study Sites (3)

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

Institut de recherches cliniques de Montréal

Montreal, Quebec, Canada

Location

Montreal Children Hospital

Montreal, Quebec, Canada

Location

Related Publications (1)

• 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.

  PMID: 26523526 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Insulin Resistance

Interventions

Exercise

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Rémi Rabasa-Lhoret, MD, PhD

  Institut de recherches cliniques de Montréal

  PRINCIPAL INVESTIGATOR

• Bruce Perkins

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 12, 2013
• First Posted: July 22, 2013
• Study Start: July 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 21, 2014

Record last verified: 2014-10

Locations

CA (3)