Effect of Basal-Bolus Closed-Loop Co-Administration of Insulin and Pramlintide on Improving the Glycemic Control in Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

Official title: A Randomized, Three-way, Crossover Study to Assess the Efficacy of Fast-acting Insulin-plus-pramlintide Closed-loop Co-administration, Regular Insulin-plus-pramlintide Closed-loop Co-administration, and Fast-acting Insulin-alone Closed-loop Infusion in Regulating Glucose Levels Over a 24-hour Period in Adults With Type 1 Diabetes in Inpatient Settings.

Status Completed

Clinical Trial Summary

The closed-loop delivery system is composed of an insulin pump, a continuous glucose sensor and a dosing algorithm that calculates the insulin dose to infuse based on sensor readings. Pramlintide is a drug and an analog of amylin, a hormone that is co-secreted with insulin in healthy individuals, and is deficient in people with type 1 diabetes. Co-injection of pramlintide with insulin at meal times improves glucose control in type 1 diabetes. Literature data suggests that regular insulin may better match the effect of pramlintide compared to rapid insulin in regulating post-prandial glucose levels.

The purpose of this study is to compare the effectiveness of 3 strategies to control your day-and-night glucose levels:

1. rapid insulin-alone closed-loop delivery;

2. rapid insulin-plus-pramlintide closed-loop delivery;

3. regular insulin-plus-pramlintide closed-loop delivery.

The primary hypotheses are:

1. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and fast-acting insulin improves glucose control compared to fast-acting insulin-alone infusion.

2. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion.

Clinical Trial Description

The closed-loop delivery system is composed of an insulin pump, a continuous glucose sensor and a dosing algorithm that calculates the insulin dose to infuse based on sensor readings. Pramlintide is a drug and an analog of amylin, a hormone that is co-secreted with insulin in healthy individuals, and is deficient in people with type 1 diabetes. Co-injection of pramlintide with insulin at meal times improves glucose control in type 1 diabetes.

Literature data suggests that the pharmacodynamics of regular insulin may better match the effect of pramlintide compared to the pharmacodynamics of fast-acting insulin. Moreover, the cost of regular insulin is significantly lower than fast-acting insulin. Therefore, if a similar (or better) glucose profile can be achieved with regular insulin-plus-pramlintide compared to fast-acting insulin-plus-pramlintide, then a co-formulation employing regular insulin should be prioritized.

Therefore, in this protocol, we aim to assess the effect of the simultaneous, closed-loop, basal-bolus infusion of pramlintide with insulin at a fixed ratio in controlling glucose levels. In the first experimental arm, we propose to infuse pramlintide with fast-acting insulin. In the second experimental arm, pramlintide will be infused with regular insulin. The control arm will be fast-acting insulin-alone closed-loop system.

The aim of the study is to assess the efficacy of the simultaneous, closed-loop, basal-bolus infusion of pramlintide with fast-acting insulin at a fixed ratio and pramlintide with regular insulin at a fixed ratio in controlling glucose levels compared to fast-acting insulin-alone closed-loop infusion.

The investigators aim to conduct a randomized, three-way, crossover trial to compare the efficacy of 1) fast-acting insulin-plus-pramlintide closed-loop delivery, 2) regular insulin-plus-pramlintide closed-loop delivery, and 3) fast-acting insulin-alone closed-loop delivery in regulating glucose levels over a period of 24 hours in a study on adults in inpatient settings. Insulin (fast-acting and regular) and pramlintide are given with fixed ratio (6 µg of pramlintide for each unit of insulin).

Before each 24-hour intervention visit, the participant's insulin therapy (basal rates and insulin-to-carbohydrate ratios) will be optimized for a minimum of 10 days, with a target of 14 days.

There will be a wash-out period of 0 to 42 days between the three intervention arms (termination of 24-hr intervention and start of next optimization period).

The primary hypotheses are:

1. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and fast-acting insulin improves glucose control compared to fast-acting insulin-alone infusion.

2. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion. ;

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

• NCT number: NCT02814123
• Study type: Interventional
• Source: McGill University
• Status: Completed
• Phase: Phase 2
• Start date: January 13, 2017
• Completion date: July 8, 2018