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

Type 1 Diabetes Clinical Trial

Official title:

An Open-label, Randomized, Cross-over Study to Assess the Efficacy of Single-hormone and Dual-hormone Closed-loop Strategy in Regulating Overnight Glucose Levels in Type 1 diabètes Adults With Hypoglycemia Unawareness and Documented Nocturnal Hypoglycemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02282254
• Other study ID #: CLASS-09
• Status: Completed
• Phase: Phase 2
• First received: October 19, 2014
• Last updated: November 8, 2016
• Start date: October 2014
• Est. completion date: July 2016

Study information

• Verified date: November 2016
• Source: Institut de Recherches Cliniques de Montreal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes
• Unconsciousness

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherches Cliniques de Montreal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of time of plasma glucose levels spent below 4 mmol/L		Up to 8 hours	No
Secondary	Percentage of time of plasma glucose levels spent between 4 and 8 mmol/L		Up to 8 hours	No
Secondary	Percentage of time of plasma glucose levels spent between 4 and 10 mmol/L		Up to 8 hours	No
Secondary	Percentage of time of plasma glucose levels spent below 3.5 mmol/L		Up to 8 hours	No
Secondary	Percentage of time of plasma glucose levels spent below 3.3. mmol/L		Up to 8 hours	No
Secondary	Percentage of time of plasma glucose levels spent above 8 mmol/L		Up to 8 hours	No
Secondary	Percentage of time of plasma glucose levels spent above 10 mmol/L		Up to 8 hours	No
Secondary	Area under the curve of plasma glucose levels spent below 4 mmol/L		Up to 8 hours	No
Secondary	Area under the curve of plasma glucose levels spent below 3.5 mmol/L		Up to 8 hours	No
Secondary	Area under the curve of plasma glucose levels spent below 3.3 mmol/L		Up to 8 hours	No
Secondary	Area under the curve of plasma glucose levels spent above 8 mmol/L		Up to 8 hours	No
Secondary	Area under the curve of plasma glucose levels spent above 10 mmol/L		Up to 8 hours	No
Secondary	Mean plasma glucose levels		Up to 8 hours	No
Secondary	Standard deviation of plasma glucose levels		Up to 8 hours	No
Secondary	Total insulin delivery		Up to 8 hours	No
Secondary	Total glucagon delivery		Up to 8 hours	No
Secondary	Number of subjects experiencing at least one hypoglycemic event requiring oral treatment		Up to 8 hours	No
Secondary	Total number of hypoglycemic events requiring treatment		Up to 8 hours	No