Clinical trial NCT02626936: Safety of Overestimation of a Meal Insulin Bolus in the Context of Dual-hormone Closed-loop Operation
Official title: A Single-blind, Randomized, Two-way, Cross-over Study to Examine the Safety of Overestimation of a Meal Insulin Bolus in the Context of Dual-hormone Closed-loop Operation Combined With a Simplified Qualitative Meal-size Estimation in Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
Artificial pancreas
Closed-loop system
Postprandial glucose control
Hypoglycemia
Insulin
Glucagon
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
First posted: 2015-12-10
Enrollment: 10
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: In previous studies, investigators have studied if a pre-meal insulin bolus based on estimated carbohydrate meal size would alleviate the burden of carbohydrate counting without a significant degradation in postprandial glucose control. With this strategy, the patient would only have to evaluate the size of the meal in terms of carbohydrate (snack, regular, large or very large) It is however important to establish safety of this simplified meal bolus approach. The safety of overestimating a meal insulin bolus in the context of single and dual-hormone CLS with the simplified meal strategy needs to be determined. Computer simulation will be used to get a reasonable estimate of risks related to over-estimation with single-hormone closed-loop while over-estimation with dual-hormone closed-loop will be tested in adults with type 1 diabètes

Investigators hypothesize that dual-hormone closed-loop with overestimated meal size bolus will not increase time below 4.0 mmol/L compared to dual-hormone closed-loop with an adequately estimated meal size bolus


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. 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).

Primary outcomes:
measure: Percentage of time below 4.0 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
Secondary outcomes:
measure: Mean glucose
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Percentage of time of glucose concentrations between 4.0 and 8.0 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Percentage of time of glucose concentrations between 4.0 and 10.0 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Percentage of time of glucose concentrations below 3.1 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Area under the curve of glucose values below 4.0 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Area under the curve of glucose values below 3.1 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Number of patients with at least one hypoglycemic event with or without symptoms
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Total number of hypoglycemic event below 3.1 mmol/L
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Total carbohydrate intake for hypoglycemia correction
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Total insulin delivery
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
measure: Total glucagon delivery
timeFrame: The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.
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: