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

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01930097
• Other study ID #: CLASS-05
• Status: Completed
• Phase: Phase 2
• First received: August 23, 2013
• Last updated: April 8, 2014
• Start date: August 2013
• Est. completion date: February 2014

Study information

• Verified date: April 2014
• Source: Institut de Recherches Cliniques de Montreal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: ethic research committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Other:
• 14 hours intervention
Subjects will be admitted at the IRCM at 6:30. Subjects will be asked to fast from midnight. At 8:00, a standardized (50g CHO for males; 30g CHO for females) meal will be served. At 12:00, a standardized (120g CHO for males; 90g CHO for females) meal will be served. At 17:00, a standardized (70g CHO for males; 50g CHO for females) meal will be served. Between meals, patients will be allowed to do sedentary activities (reading, watching television, and playing video games, etc).

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Cliniques de Montreal	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The positive incremental area under the curve of postprandial glucose excursions	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.	4 hours after meal intake	No
Secondary	Mean plasma glucose		8h00 to 21h00	No
Secondary	Incremental two hours postprandial glucose		2 hours after meal intake	No
Secondary	Incremental postprandial peak-glucose values		8h00 to 21h00	No
Secondary	Percentage of time of plasma glucose levels between 4.0 and 10.0 mmol/L		8h00 to 21h00	No
Secondary	Percentage of time of plasma glucose levels spent above 10.0 mmol/L		8h00 to 21h00	No
Secondary	Percentage of time of plasma glucose levels spent below 4.0 mmol/L		8h00 to 21h00	No
Secondary	Total insulin delivery		8h00 to 21h00	No
Secondary	Total glucagon delivery		8h00 to 21h00	No
Secondary	Standard deviation of glucose levels		8h00 to 21h00	No
Secondary	Percentage of time of plasma glucose concentrations below 3.5 mmol/L		8h00 to 21h00	No
Secondary	Percentage of time of plasma glucose concentrations above 14 mmol/L		8h00 to 21h00	No
Secondary	Mean plasma insulin concentration		8h00 to 21h00	No
Secondary	Mean plasma glucagon concentration		8h00 to 21h00	No
Secondary	Number of patients experiencing hypoglycemia requiring oral treatment		8h00 to 21h00	No
Secondary	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	No