Closed-loop Control of Overnight Glucose Levels (Artificial Pancreas) in Children With Type 1 Diabetes in a Diabetes Camp

• ClinicalTrials.gov Identifier: NCT02189694
• Recruitment Status: Completed
• First Posted: July 14, 2014
• Last Update Posted: September 3, 2014
• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborator: Montreal Children's Hospital of the MUHC
• Information provided by (Responsible Party): Rémi Rabasa-Lhoret, Institut de Recherches Cliniques de Montreal

Study Description

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 children with type 1 diabetes in a diabetes camp.

The investigators hypothesized that dual-hormone closed-loop strategy reduces the time spent in hypoglycemia in children with type 1 diabetes (T1D) compared to single-hormone closed-loop strategy, which in turn is more effective than the conventional pump therapy to reduce time spent in hypoglycemia

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: Single-hormone closed-loop strategy; Device: Dual-hormone closed-loop strategy; Device: Insulin pump therapy	Phase 2

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.

The investigators aim to conduct a randomized three-way cross-over trial comparing single hormone closed-loop strategy, dual-hormone closed-loop strategy and the conventional pump therapy. The investigators aim to compare the three interventions for 3 consecutive nights in children with type 1 diabetes in a diabetes camp.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (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 Overnight Glucose Levels in Children With Type 1 Diabetes in a Diabetes Camp
• Study Start Date: June 2014
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Insulin pump therapy; Glucose levels will be controlled for 3 consecutive nights using insulin pump therapy. Subjects will carry on with their normal conventional insulin pump therapy and will be allowed to freely implement therapeutic adjustments..	Device: Insulin pump therapy; Subjects will use conventional pump therapy to regulate glucose levels. Insulin Aspart (Novorapid, Novo Nordisk) will be used.
Active Comparator: Single-hormone closed-loop strategy; Glucose levels will be controlled by single-hormone closed-loop strategy for 3 consecutive nights. A member of the research team will be present at the diabetic camp to ensure protocol implementation and patient's safety. Glucose levels will be controlled by single-hormone closed-loop strategy between 22:00 until 7:00 next morning. Glucose sensor reading will be entered manually into the computer every 10 minutes. The computer will generate a recommendation for the basal rates of insulin delivery. Pump's parameters will then be changed manually to implement the computer generated recommendations.	Device: Single-hormone closed-loop strategy; Variable subcutaneous insulin infusion rates will be used to regulate glucose levels. Insulin Aspart (Novorapid, Novo Nordisk) will be used.
Active Comparator: Dual-hormone closed-loop strategy; Glucose levels will be controlled by dual-hormone closed-loop strategy for 3 consecutive nights. A member of the research team will be present at the diabetic camp to ensure protocol implementation and patient's safety. Glucose levels will be controlled by dual-hormone closed-loop strategy between 22:00 until 7:00 next morning. Glucose sensor readings will be entered manually into the computer every 10 minutes. The computer will generate a recommendation for the basal rates of insulin delivery and glucagon mini-boluses. Pumps' parameters will then be changed manually to implement the computer generated recommendations.	Device: Dual-hormone closed-loop strategy; Variable subcutaneous insulin and glucagon infusion rates will be used to regulate glucose levels. Insulin Aspart (Novorapid, Novo Nordisk) and Glucagon (Eli Lilly and Company) will be used.

Outcome Measures

Primary Outcome Measures :

1. Percentage of time of glucose levels spent below 4.0 mmol/L. [ Time Frame: Up to 8 hours ]

Secondary Outcome Measures :

1. Percentage of time of glucose levels spent between 4.0 and 8.0 mmol/L [ Time Frame: Up to 8 hours ]
2. Percentage of time of glucose levels spent below 3.5 mmol/L [ Time Frame: Up to 8 hours ]
3. Percentage of time of glucose levels spent below 3.3 mmol/L [ Time Frame: Up to 8 hours ]
4. Percentage of time of glucose levels spent above 8 mmol/L [ Time Frame: Up to 8 hours ]
5. Percentage of time of glucose levels spent above 10 mmol/L. [ Time Frame: Up to 8 hours ]
6. Area under the curve of glucose levels below 4.0 mmol/L [ Time Frame: Up to 8 hours ]
7. Area under the curve of glucose levels below 3.5 mmol/L [ Time Frame: Up to 8 hours ]
8. Area under the curve of glucose levels below 3.3 mmol/L [ Time Frame: Up to 8 hours ]
9. Area under the curve of glucose levels above 8.0 mmol/L [ Time Frame: Up to 8 hours ]
10. Area under the curve of glucose levels above 10.0 mmol/L. [ Time Frame: Up to 8 hours ]
11. Mean glucose levels. [ Time Frame: Up to 8 hours ]
12. Standard deviation of glucose levels [ Time Frame: Up to 8 hours ]
    Measure of glucose variability.
13. Total insulin delivery [ Time Frame: Up to 8 hours ]
14. Hypoglycemic risk assessed by the total number of hypoglycemic event (> 15 minutes) below 3.1 mmol/L [ Time Frame: Up to 8 hours ]
15. Hypoglycemic risk assessed by the number of patients experiencing at least one hypoglycemic event (> 15 minutes) below 3.1 mmol/L [ Time Frame: Up to 8 hours ]

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or females between the 8 and 17 years of old.
• Clinical diagnosis of type 1 diabetes for at least one year. The subject will have been on insulin pump therapy for at least 3 months.
• HbA1c ≤ 11.0%.

Exclusion Criteria:

• Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
• Severe hypoglycemic episode within two weeks of inclusion in the study. A severe hypoglycemic episode is defined as loss of conscience, seizure or a hospital emergency visit.
• Current use of oral glucocorticoid medication (except low stable dose according to investigator judgement). Stable doses of inhaled steroids are acceptable.
• Known or suspected allergy to the trial products.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
• Failure to comply with team's recommendations (e.g. not willing to use trial pump, etc).

Contacts and Locations

Locations

Canada, Quebec

Institut de recherches cliniques de Montréal

Montreal, Quebec, Canada, H2W 1R7

Sponsors and Collaborators

Institut de Recherches Cliniques de Montreal

Montreal Children's Hospital of the MUHC

Investigators

• Principal Investigator: Rémi Rabasa-Lhoret, MD, PhD; Institut de recherches cliniques de Montréal

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Haidar A, Legault L, Matteau-Pelletier L, Messier V, Dallaire M, Ladouceur M, Rabasa-Lhoret R. Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2015 Aug;3(8):595-604. doi: 10.1016/S2213-8587(15)00141-2. Epub 2015 Jun 8.

• Responsible Party: Rémi Rabasa-Lhoret, Associate professor of Medicine, Institut de Recherches Cliniques de Montreal
• ClinicalTrials.gov Identifier: NCT02189694
• Other Study ID Numbers: CLASS-08
• First Posted: July 14, 2014
• Last Update Posted: September 3, 2014
• Last Verified: September 2014

Keywords provided by Rémi Rabasa-Lhoret, 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; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists