Clinical trial NCT04031599: Assessment of the Efficacy of the Artificial Pancreas Combined With a Qualitative Meal Size Estimation to Control Postprandial Glucose Levels
Official title: An Open-label, Randomized, Crossover Trial to Assess the Efficacy of Single-hormone Closed-loop System With a Rapid Acting Insulin Analogue Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation in Regulating Glucose Levels in Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
Artificial pancreas
Closed-loop system
Insulin
Postprandial glucose
Exercise
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
First posted: 2019-07-24
Enrollment: 30
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 glycemic excursions are major determinants of overall glycemic control in type 1 diabetes. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels. accurate carbohydrate counting is considered by patients as a significant burden and frustrating task.

The closed-loop system (CLS) 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.

The objective of this study is to compare the efficacy of two strategies to regulate glucose levels in outpatient settings in adults with type 1 diabetes: 1) single-hormone CLS with rapid acting insulin analogue combined with carbohydrate counting; 2) single-hormone CLS with rapid acting insulin analogue combined with simplified qualitative meal-size estimation.

A sub-study will also be proposed to participants. Postprandial exercise combines two situations complicating CLS operation: a high plasma insulin due to insulin on-board related to meal boluses and rapid blood glucose changes (postprandial blood glucose excursion and then drop during exercise) making input from the glucose sensor less accurate. The objective of this sub-study will be to explore the safety and efficacy of the CLS using the combined strategy of pre-meal exercise announcement and meal bolus reduction of 33% when exercise is performed 1 hour compared to 2 hours post meal time.


Eligibility criteria: Inclusion criteria

1. Males and females ≥ 18 years of old.
2. Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
3. The subject will have been on insulin pump therapy for at least 3 months.
4. Currently using, or willing to switch to Lispro U100 or Aspart for the duration of the study.
5. HbA1c \< 10%.

Exclusion criteria

1. Clinically significant nephropathy, neuropathy (e.g. known or suspected gastroparesis) or retinopathy (e.g. proliferative retinopathy) as judged by the investigator
2. Recent (\< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery
3. Anticipated need to use acetaminophen during interventions with the closed-loop system
4. Pregnancy (ongoing or current attempt to become pregnant)
5. Breastfeeding
6. No nearby third party for assistance if needed (e.g. severe hypoglycemia glucagon treatment)
7. Plans to go abroad or travel at more than 3 hours distance from Montreal during the trial period
8. Severe hypoglycemic episode within two weeks of screening or during the run-in period
9. Severe hyperglycemic episode requiring hospitalization in the last 3 months
10. Current use of glucocorticoid medication (except low stable dose and inhaled steroids)
11. Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, 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.
12. Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months and appropriate ketone testing performed.
13. Known or suspected allergy to the trial products
14. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator
15. Anticipation of a significant change in exercise regimen between admission and end of the trial (i.e. starting or stopping an organized sport)
16. In the opinion of the investigator, a participant who in unable or unwilling to observed the contraindications of the study devices

Primary outcomes:
measure: Percentage of time of glucose levels spent between 3.9 and 10.0 mmol/L
timeFrame: 504 hours
measure: Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)
timeFrame: 3.5 or 4.5 hours
Secondary outcomes:
measure: Percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L
timeFrame: 504 hours
measure: Percentage of time of glucose levels spent below 3.9 mmol/L
timeFrame: 504 hours
measure: Percentage of time of glucose levels spent below 3.3 mmol/L
timeFrame: 504 hours
measure: Percentage of time of glucose levels spent below 2.8 mmol/L
timeFrame: 504 hours
measure: Percentage of time of glucose levels spent above 10.0 mmol/L
timeFrame: 504 hours
measure: Percentage of time of glucose levels spent above 13.9 mmol/L
timeFrame: 504 hours
measure: Percentage of time of glucose levels spent above 16.7 mmol/L
timeFrame: 504 hours
measure: Mean glucose levels
timeFrame: 504 hours
measure: Fasting glucose levels
timeFrame: 504 hours
measure: Standard deviation of glucose levels
timeFrame: 504 hours
measure: Standard deviation of insulin delivery
timeFrame: 504 hours
measure: Coefficient of variance of glucose levels
timeFrame: 504 hours
measure: Coefficient of variance of insulin delivery
timeFrame: 504 hours
measure: Between-day variability in glucose levels
timeFrame: 504 hours
measure: Between-day variability in insulin delivery
timeFrame: 504 hours
measure: Total insulin delivery
timeFrame: 504 hours
measure: Number of hypoglycemic events less than 3.1 mmol/L
timeFrame: 504 hours
measure: Number of nights with hypoglycemic events less than 3.1 mmol/L
timeFrame: 126 hours
measure: Number of days with hypoglycemic events less than 3.1 mmol/L
timeFrame: 252 hours
measure: Total number of hours of sensor availability
timeFrame: 378 hours
measure: Percentage of time of sensor availability
timeFrame: 504 hours
measure: 2-hour postprandial glucose levels over the last 3 days of the intervention.
timeFrame: 18 hours
measure: Average number of days per participant requiring study team support for at least one technical problem
timeFrame: 21 days
measure: Number of hours and percentage of time in open-loop and closed-loop modes
timeFrame: 504 hours
measure: Average number of phone calls per participant related to CLS technical issues
timeFrame: 504 hours
measure: Decrease in plasma glucose levels during exercise (sub-study)
timeFrame: 1 hour
measure: Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)
timeFrame: 2 or 3 hours
measure: Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent above 13.9 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
timeFrame: 1 or 2 hours
measure: Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
timeFrame: 1 hour
measure: Number of patients experiencing hypoglycemia requiring treatment (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent above 13.3 mmol/L (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
timeFrame: 1 hour
measure: Percentage of time of plasma glucose levels spent below 3.9 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Percentage of time of plasma glucose levels spent below 3.3 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Percentage of time of plasma glucose levels spent below 3.0 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Percentage of time of plasma glucose levels spent between 3.9 and 10.0 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Percentage of time of plasma glucose levels spent above 10.0 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Percentage of time of plasma glucose levels spent above 13.3 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Percentage of time of plasma glucose levels spent above 16.7 mmol/L (sub-study)
timeFrame: 1.5 hour
measure: Number of patients experiencing hypoglycemia requiring treatment (sub-study)
timeFrame: 3.5 or 4.5 hours
measure: Mean time (minutes) to the first hypoglycemic event (sub-study)
timeFrame: 1 hour
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Montreal Clinical Research Institute
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: Montreal Clinical Research Institute
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References: