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

NCT ID: NCT01905020

Last Updated: 2014-10-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2014-09-30

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).

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Conventional insulin pump therapry

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

Group Type: ACTIVE_COMPARATOR

Carbohydrate-rich meal

Intervention Type: 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.

Exercise

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Carbohydrate-rich meal

Intervention Type: 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.

Exercise

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Carbohydrate-rich meal

Intervention Type: 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.

Exercise

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Montreal Children's Hospital of the MUHC

OTHER

Sponsor Role: collaborator

Mount Sinai Hospital, New York

OTHER

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: collaborator

Institut de Recherches Cliniques de Montreal

OTHER

Sponsor Role: lead

Responsible Party

Rémi Rabasa-Lhoret

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rémi Rabasa-Lhoret, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institut de recherches cliniques de Montréal

Bruce Perkins

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Institut de recherches cliniques de Montréal

Montreal, Quebec, Canada

Montreal Children Hospital

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 26523526 (View on PubMed)

Other Identifiers

CLASS-04

Identifier Type: -

Identifier Source: org_study_id