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Closed-loop Control of Glucose Levels After Meal Intake in Adults With Type 1 Diabetes

Phase 2
Completed
Conditions
Type 1 Diabetes
Registration Number
NCT01930097
Lead Sponsor
Institut de Recherches Cliniques de Montreal
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Primary Outcome Measures
NameTimeMethod
The positive incremental area under the curve of postprandial glucose excursions4 hours after meal intake

The positive incremental area under the curve (IAUC, as compared to pre-meal glucose value) of the 4-hr postprandial glucose excursions for the breakfast, lunch and dinner meals.

Secondary Outcome Measures
NameTimeMethod
Incremental postprandial peak-glucose values8h00 to 21h00
Mean plasma glucose8h00 to 21h00
Incremental two hours postprandial glucose2 hours after meal intake
Percentage of time of plasma glucose levels between 4.0 and 10.0 mmol/L8h00 to 21h00
Percentage of time of plasma glucose levels spent above 10.0 mmol/L8h00 to 21h00
Percentage of time of plasma glucose levels spent below 4.0 mmol/L8h00 to 21h00
Total insulin delivery8h00 to 21h00
Total glucagon delivery8h00 to 21h00
Standard deviation of glucose levels8h00 to 21h00
Percentage of time of plasma glucose concentrations below 3.5 mmol/L8h00 to 21h00
Percentage of time of plasma glucose concentrations above 14 mmol/L8h00 to 21h00
Mean plasma insulin concentration8h00 to 21h00
Mean plasma glucagon concentration8h00 to 21h00
Number of patients experiencing hypoglycemia requiring oral treatment8h00 to 21h00
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.4 hours after meal intake

Trial Locations

Locations (1)

Institut de recherches cliniques de Montréal

🇨🇦

Montreal, Quebec, Canada

Institut de recherches cliniques de Montréal
🇨🇦Montreal, Quebec, Canada

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