Comparison of Closed-loop Operation After Morning Meal With and Without Carbohydrate Counting (CLASS02)

An Open-label, Randomized Two-way, Cross-over Study to Compare Meal-and-carbohydrate-announcement Strategy Versus Meal-announcement Strategy During Closed-loop Regulation of Glucose Levels in a Morning Meal in Adults With Type-1 Diabetes.

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 main goal 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.

Each patient will be admitted twice to a clinical research facility. In one visit, patients will eat a morning meal 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 other visit, patients will eat the same meal 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. If post-meal glucose levels were indifferent between the two visits, then this would suggest that carbohydrate counting may not be necessary during closed-loop operation as the closed-loop system will give any remaining insulin needed to cover the glucose absorbed from the meal. Twelve subjects will be enrolled in this study.

Study Overview

• Status: Completed
• Conditions: Type-1 Diabetes
• Intervention / Treatment: Device: Dual Hormone closed-loop system

• Study Type: Interventional
• Enrollment: 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Institut de recherches cliniques de Montréal (IRCM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ≥ 18 and ≤ 65 years of old.
• Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment and medical history (e.g. history of acido-ketosis, etc.); C peptide level and antibody determinations are not needed.
• 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 nephropathy, neuropathy (especially clinically significant gastroparesis) or retinopathy as judged by the investigator.
• Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• Pregnancy.

• Severe hypoglycemic episode within two weeks of screening.

  • Medication likely to affect with the interpretation of the results: Prandase, Victoza, Byetta and Symlin

• Known or suspected allergy to the trial products or meal contents.
• 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
• Problems with venous access

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CHO-independent partial insulin bolus with closed-loop	Device: Dual Hormone closed-loop system; The closed-loop system is composed of three components: continuous glucose system, insulin infusion pumps that infuses insulin and glucagon and a control algorithm that decides on the infusion rates based on sensor readings.
Active Comparator: CHO-dependent full insulin bolus combined with closed-loop	Device: Dual Hormone closed-loop system; The closed-loop system is composed of three components: continuous glucose system, insulin infusion pumps that infuses insulin and glucagon and a control algorithm that decides on the infusion rates based on sensor readings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incremental area under the curve of plasma glucose concentration as compared to pre-meal glucose value of the postprandial glucose excursions	0-300min

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of postprandial time of plasma glucose concentrations spent in the high range (above 10.0 mmol/l).	0-300 min
Mean plasma glucose concentration.
Total insulin delivery
Total glucagon delivery
Plasma glucose concentration and incremental plasma glucose concentration at 2 hours postmeal
Postprandial peak and incremental postprandial peak of plasma glucose concentration
Percentage of time of plasma glucose concentrations spent in target range. Target range is defined to be between 4.0 and 10.0 mmol/l for 150 minutes postmeal and between 4.0 and 8.0 mmol/l afterwards
Percentage of postprandial time of plasma glucose concentrations spent in the low range (below 4.0mmol/l)	0-300min

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: McGill University; Montreal Children's Hospital of the MUHC

Publications and helpful links

General Publications

• Haidar A, Farid D, St-Yves A, Messier V, Chen V, Xing D, Brazeau AS, Duval C, Boulet B, Legault L, Rabasa-Lhoret R. Post-breakfast closed-loop glucose control is improved when accompanied with carbohydrate-matching bolus compared to weight-dependent bolus. Diabetes Metab. 2014 Jun;40(3):211-4. doi: 10.1016/j.diabet.2013.12.001. Epub 2014 Mar 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: January 24, 2012
• First Submitted That Met QC Criteria: January 25, 2012
• First Posted (Estimate): January 26, 2012

Study Record Updates

• Last Update Posted (Estimate): December 10, 2012
• Last Update Submitted That Met QC Criteria: December 7, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: CLASS-02