Clinical trial NCT02416765: Closed-loop Control of Postprandial Glucose Levels in 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 Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Closed-loop strategy
Artificial pancreas
Postprandial glucose
Insulin
Glucagon
Hypoglycemia
Type 1 diabetes
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
First posted: 2015-04-15
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Postprandial meal glucose control with closed-loop systems (CLS) still needs some improvements. In the postprandial period, sensor delay in detecting blood glucose rise after a meal together with delays in insulin absorption expose patients to early risk of hyperglycemia and then to late-postprandial hypoglycemia. Glucagon infusion in dual-hormone CLS has the potential to improve post-meal control as compared to single-hormone CLS allowing a better glucose excursion related to a more aggressive insulin infusion while minimizing hypoglycemic risk. Several approaches have been tested for the determination of prandial boluses during closed-loop operation.

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 adult patients with type 1 diabetes.

The investigators hypothesize that in outpatient free-living conditions: 1) Dual-hormone CLS with partial boluses is equivalent to dual-hormone CLS with full boluses in terms of mean glucose; 2) Single-hormone CLS with partial boluses is equivalent to single-hormone CLS with full boluses in terms of mean glucose. Secondary hypothesis are: 3) Dual-hormone CLS with partial boluses will decrease time in hypoglycemia compared to single-hormone CLS with partial boluses; 4) Dual-hormone CLS with partial boluses is better than sensor-augmented pump therapy in terms of mean glucose; 5) Single-hormone CLS with partial boluses is better than sensor-augmented pump therapy in terms of mean glucose.


Eligibility criteria: Inclusion Criteria:

1. Males and females ≥ 18 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.

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. Ongoing 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 glucose levels as measured by the glucose sensor.
timeFrame: 15 hours
Secondary outcomes:
measure: Mean glucose levels as measured by the glucose sensor
timeFrame: 15 hours
measure: Percentage of time of sensor glucose concentrations between 4 and 8 mmol/L
timeFrame: 15 hours
measure: Percentage of time of sensor glucose concentrations between 4 and 10 mmol/L
timeFrame: 15 hours
measure: Percentage of time of sensor glucose concentrations above 10 mmol/L
timeFrame: 15 hours
measure: Percentage of time of sensor glucose concentrations above 14 mmol/L
timeFrame: 15 hours
measure: Percentage of time of glucose levels spent below 4 mmol/L
timeFrame: 15 hours
measure: Percentage of time of glucose levels spent below 3.1 mmol/L
timeFrame: 15 hours
measure: Area under the curve of glucose values below 4 mmol/L
timeFrame: 15 hours
measure: Area under the curve of glucose values below 3.1 mmol/L
timeFrame: 15 hours
measure: Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms
timeFrame: 15 hours
measure: Total number of hypoglycemic event below 3.1 mmol/L
timeFrame: 15 hours
measure: Total insulin delivery
timeFrame: 15 hours
measure: Total glucagon delivery
timeFrame: 15 hours
measure: Standard deviation of glucose levels
timeFrame: 15 hours
measure: Total carbohydrate intake
timeFrame: 15 hours
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: