Clinical trial NCT02490098: Closed-loop Control of Postprandial Glucose Levels in Children and Adults With Type 1 Diabetes
Official title: An Open-label, Randomized, Five-way, Cross-over Study to Compare the Efficacy of Single- and Dual-hormone Closed-loop Operations Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation, and Sensor-augmented Pump Therapy in Regulating Glucose Levels in Children and Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
Closed-loop system
Artificial pancreas
Insulin
Glucagon
Hypoglycemia
Postprandial glucose
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2015-07-03
Enrollment: 0
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Current intensive insulin therapy in T1D involves prandial insulin boluses depending on the carbohydrate content of each ingested meal. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Therefore, accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels in type 1 diabetes in order to avoid too much or too little insulin resulting in hypoglycemia and hyperglycemia, respectively. Precision of carbohydrate counting is associated with better glycemic control. However, accurate carbohydrate counting is a challenging task for many patients with type 1 diabetes. Recent developments of continuous glucose sensors and insulin infusion pumps have motivated the research toward "closed-loop'' strategies to regulate glucose levels in patients with type 1 diabetes. In a closed-loop strategy, the pump insulin infusion rate is altered based on a computer generated recommendation that rely on continuous glucose sensor readings. A dual-hormone closed-loop strategy has also been recently proposed to regulate glucose levels. In a dual-hormone strategy, subcutaneous insulin delivery is accompanied by subcutaneous glucagon infusion. Postprandial meal glucose control with closed-loop strategy still needs some improvements. The objective of this study is to test in outpatient unrestricted settings whether, in the context of closed-loop strategy, conventional meal carbohydrate counting could be reduced to a simplified qualitative meal size estimation without a significant degradation in overall glycemic control in children and adult patients with type 1 diabetes. The investigators hypothesize that 1) dual-hormone closed-loop strategy with qualitative meal size estimation is equivalent to dual-hormone closed-loop strategy with CHO counting in terms of mean glucose; 2) single-hormone closed-loop strategy with qualitative meal size estimation is equivalent to single-hormone closed-loop strategy with CHO counting in terms of mean glucose;


Eligibility criteria: Inclusion Criteria:

1. Males and females ≥ 8 years 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 and currently using a fast actin insulin analog (Lispro, Aspart or Guilisine).
4. Last (less than 3 months) HbA1c ≤ 10%.
5. Currently using carbohydrate counting as the meal insulin dose strategy.
6. Live in the area of Montreal

Exclusion Criteria:

1. Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator.
2. Recent (\< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
3. Pregnancy.
4. Severe hypoglycemic episode within 1 month of screening.
5. Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, SGLT-2 inhibitors and DPP-4 inhibitors) if not at a stable dose for 3 months. Otherwise, these medications are acceptable and will be kept stable during the entire protocol.
6. Oral steroids unless patients present a low stable dose (e.g. 10 mg or less of prednisone per day or physiological doses, less than 35 mg/day, of hydrocortisone Cortef®). Inhale steroids at stable dose in the last month are acceptable.
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 (e.g. unstable psychiatric condition).
8. Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).
9. Living or planned travel outside Montreal (\> 1h of driving) area during closed-loop procedures.

Primary outcomes:
measure: Mean day-and-night glucose levels
timeFrame: 6 days
Secondary outcomes:
measure: Percentage of time of glucose levels between 4.0 and 8.0 mmol/L
timeFrame: 6 days
measure: Percentage of time of glucose levels between 4.0 and 10.0 mmol/L
timeFrame: 6 days
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: 6 days
measure: Percentage of time of glucose levels above 14.0 mmol/L
timeFrame: 6 days
measure: Percentage of time of glucose levels spent below 4.0 mmol/L
timeFrame: 6 days
measure: Percentage of time of glucose levels spent below 3.1 mmol/L
timeFrame: 6 days
measure: Area under the curve of glucose values below 4.0 mmol/L
timeFrame: 6 days
measure: Area under the curve of glucose values below 3.1 mmol/L
timeFrame: 6 days
measure: Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms
timeFrame: 6 days
measure: Total number of hypoglycemic event below 3.1 mmol/L
timeFrame: 6 days
measure: Total insulin delivery
timeFrame: 6 days
measure: Total glucagon delivery
timeFrame: 6 days
measure: Standard deviation of glucose levels
timeFrame: 6 days
measure: Total carbohydrate intake
timeFrame: 6 days
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References: