Closed-loop Control of Overnight Glucose Levels (Artificial Pancreas) in Type 1 Diabètes Adults With Hypoglycemia Unawareness and Documented Nocturnal Hypoglycemia

NCT ID: NCT02282254

Last Updated: 2016-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2016-07-31

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 strategy would regulate glucose levels through the infusion of two hormones: insulin and glucagon.

The main objective of this project is to compare the efficacy of single-hormone and dual-hormone closed-loop strategy to regulate overnight glucose levels in a in-patient study in type 1 diabetes adults with hypoglycemia unawareness and documented nocturnal hypoglycemia.

The investigators hypothesized that dual-hormone closed-loop strategy is more effective in regulating overnight glucose levels compared to single-hormone closed-loop strategy.

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 strategy would regulate glucose levels through the infusion of two hormones: insulin and glucagon.

The investigators aim to conduct the 1st randomized cross-over trial comparing single- hormone and dual-hormone closed-loop strategy to regulate overnight glucose levels. The investigators aim to compare the two interventions for 10 hours in two subgroups of adults with type 1 diabètes. Patients from both subgroups will present documented nocturnal hypoglycemia. One subgroup will consist of patients with hypoglycemia unawareness while the other subgroup will consist of patients with hypoglycemia unawareness. This study will allow to determine if there is a greater benefit of a closed-loop strategy in a higher-risk hypoglycemia unaware group.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Hypoglycemia unawareness; Nocturnal hypoglycemia; Closed-loop strategy; Artificial pancreas; Glucagon; Hypoglycemia; Insulin

Study Design

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

Study Groups

Single-hormone closed-loop strategy

Group Type: ACTIVE_COMPARATOR

Overnight intervention

Intervention Type: OTHER

Subjects will be admitted at the research facility at 19:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. On dual-hormone closed-loop visits, glucagon will be reconstituted according to the manufacturer's instructions and a MiniMed® Paradigm® Veo™ pump containing the glucagon solution will be installed. At 20:30, a snack containing 20g of carbohydrate will be given. Closed-loop strategy will start at 20:00 until 7:00 next morning. A glucose sensor reading will be entered manually in a tablet every 10 minutes. The tablet will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses (glucagon recommendations will only be generated during the dual hormone closed-loop visits). Pumps' parameters will then be changed manually to implement the tablet generated recommendations.

Dual-hormone closed-loop strategy

Group Type: ACTIVE_COMPARATOR

Overnight intervention

Intervention Type: OTHER

Subjects will be admitted at the research facility at 19:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. On dual-hormone closed-loop visits, glucagon will be reconstituted according to the manufacturer's instructions and a MiniMed® Paradigm® Veo™ pump containing the glucagon solution will be installed. At 20:30, a snack containing 20g of carbohydrate will be given. Closed-loop strategy will start at 20:00 until 7:00 next morning. A glucose sensor reading will be entered manually in a tablet every 10 minutes. The tablet will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses (glucagon recommendations will only be generated during the dual hormone closed-loop visits). Pumps' parameters will then be changed manually to implement the tablet generated recommendations.

Interventions

Overnight intervention

Subjects will be admitted at the research facility at 19:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. On dual-hormone closed-loop visits, glucagon will be reconstituted according to the manufacturer's instructions and a MiniMed® Paradigm® Veo™ pump containing the glucagon solution will be installed. At 20:30, a snack containing 20g of carbohydrate will be given. Closed-loop strategy will start at 20:00 until 7:00 next morning. A glucose sensor reading will be entered manually in a tablet every 10 minutes. The tablet will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses (glucagon recommendations will only be generated during the dual hormone closed-loop visits). Pumps' parameters will then be changed manually to implement the tablet generated recommendations.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Males and females ≥ 18 years of old.

2. Clinical diagnosis of type 1 diabetes for at least one year.

3. The subject will have been on insulin pump therapy for at least 3 months.

4. HbA1c ≤ 12%.

5. Hypoglycemia awareness or unawareness assessed by a questionnaire.

6. Documented NH during the run-in period.

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. Pregnancy.

4. Severe hypoglycemic episode within two weeks of screening.

5. Current use of glucocorticoid medication (except low stable dose).

6. Known or suspected allergy to the trial products or snack contents.

7. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

8. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).

9. Failure to comply with team's recommendations (e.g. not willing to eat snacks, not willing to change pump parameters, etc).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

Remi Rabasa-Lhoret

Role: PRINCIPAL_INVESTIGATOR

Institut de recherches cliniques de Montréal

Locations

Institut de recherches cliniques de Montréal

Montreal, Quebec, Canada

Countries

Canada

References

Abitbol A, Rabasa-Lhoret R, Messier V, Legault L, Smaoui M, Cohen N, Haidar A. Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial. Diabetes Technol Ther. 2018 Mar;20(3):189-196. doi: 10.1089/dia.2017.0353. Epub 2018 Feb 2.

Reference Type: DERIVED

PMID: 29393675 (View on PubMed)

Other Identifiers

CLASS-09

Identifier Type: -

Identifier Source: org_study_id