Clinical trial NCT01930097: Closed-loop Control of Glucose Levels After Meal Intake in Adults With Type 1 Diabetes
Official title: An Open-label, Randomized, Three-way, Cross-over Study to Compare the Efficacy of Closed-loop Operation Combined With Meal-and-carbohydrate-announcement Closed-loop Operation Combined With Meal-announcement, and Conventional 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: Type 1 diabetes
Hypoglycemia
Insulin
Glucagon
Closed-loop system
Artificial pancreas
Carbohydrate counting
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2013-08-28
Enrollment: 12
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: 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 dosage based on the sensor's readings. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormones: insulin and glucagon.

The objective of this project is to assess whether a dual-hormone closed-loop strategy would alleviate the burden of carbohydrate counting from patients with type 1 diabetes (T1D) without a significant degradation in post-meal glucose control.

Our primary hypothesis is that meal-announcement strategy (pre-meal CHO-independent bolus) is equivalent to meal-and-carbohydrate-announcement strategy (full CHO-matching bolus) during closed-loop regulation of glucose levels in adults with T1D. Our secondary hypothesis is that closed-loop strategy with meal-announcement strategy (pre-meal CHO-independent bolus) or meal-and-carbohydrate-announcement strategy (full CHO-matching bolus) is better than conventional pump treatment in regulation of glucose levels in adults with T1D.

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.

Each patient will be admitted three times to a clinical research facility. In the meal-and-carbohydrate-announcement visit, patients will eat 3 meals accompanied with a matching insulin bolus (depending on the carbohydrate content of the meal) and glucose levels will be subsequently regulated using dual-hormone closed-loop system. In the meal-announcement visit, patients will eat the 3 same meals but will inject only a partial insulin bolus (not depending on carbohydrate content of the meal) and the remaining needed insulin will be delivered based on glucose sensor excursions as part of closed-loop operation. In the control visit, patients will use conventional pump therapy to regulate glucose levels.

Eligibility criteria: Inclusion Criteria:

* Males and females ≥ 18 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.
* Last (less than 3 months) HbA1c ≤ 12%.

Exclusion Criteria:

* 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.
* Recent (\< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
* Ongoing pregnancy.
* Severe hypoglycemic episode within two weeks of screening.
* Medication likely to affect with the interpretation of the results because of their well known impact on gastric emptying: Motilium®, Prandase®, Victoza®, Byetta® and Symlin®.
* Known or suspected allergy to the trial products, meal contents including nuts, peanuts, dairy products or eggs.
* Unusual nutritional habits (e.g. vegetarians)
* 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 eat snack, not willing to change pump parameters, etc).
* Unreliable carbohydrate counting or lack of insulin to carbohydrate ratios
* Problems with venous access

Primary outcomes:
measure: The positive incremental area under the curve of postprandial glucose excursions
timeFrame: 4 hours after meal intake
Secondary outcomes:
measure: Mean plasma glucose
timeFrame: 8h00 to 21h00
measure: Incremental two hours postprandial glucose
timeFrame: 2 hours after meal intake
measure: Incremental postprandial peak-glucose values
timeFrame: 8h00 to 21h00
measure: Percentage of time of plasma glucose levels between 4.0 and 10.0 mmol/L
timeFrame: 8h00 to 21h00
measure: Percentage of time of plasma glucose levels spent above 10.0 mmol/L
timeFrame: 8h00 to 21h00
measure: Percentage of time of plasma glucose levels spent below 4.0 mmol/L
timeFrame: 8h00 to 21h00
measure: Total insulin delivery
timeFrame: 8h00 to 21h00
measure: Total glucagon delivery
timeFrame: 8h00 to 21h00
measure: Standard deviation of glucose levels
timeFrame: 8h00 to 21h00
measure: Percentage of time of plasma glucose concentrations below 3.5 mmol/L
timeFrame: 8h00 to 21h00
measure: Percentage of time of plasma glucose concentrations above 14 mmol/L
timeFrame: 8h00 to 21h00
measure: Mean plasma insulin concentration
timeFrame: 8h00 to 21h00
measure: Mean plasma glucagon concentration
timeFrame: 8h00 to 21h00
measure: Number of patients experiencing hypoglycemia requiring oral treatment
timeFrame: 8h00 to 21h00
measure: Incremental area under the curve of the 4-hr postprandial glucose excursions but the reference glucose is set to 5.0 mmol/L if premeal glucose is less than 5.0 mmol/L.
timeFrame: 4 hours after meal intake
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, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gingras V, Rabasa-Lhoret R, Messier V, Ladouceur M, Legault L, Haidar A. Efficacy of dual-hormone artificial pancreas to alleviate the carbohydrate-counting burden of type 1 diabetes: A randomized crossover trial. Diabetes Metab. 2016 Feb;42(1):47-54. doi: 10.1016/j.diabet.2015.05.001. Epub 2015 Jun 10.