Clinical trial NCT00797823
Conditions: Type 1 Diabetes
Keywords: diabetes pancreas beta cell glucagon insulin hypoglycemia
Sponsor: Legacy Health System
Start date: 2008-11-01; Completion date: 2009-09-01
Enrollment: 14 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This study aims to test an insulin and glucagon delivery algorithm designed to be used in conjunction with a continuous glucose monitoring system. This combined glucose sensing/hormone delivery approach is a step on the way to eventual development of an artificial (or automated) pancreas. The insulin and glucagon delivery algorithm is based on the difference between the current blood glucose and the target glucose (proportional error) and the rate of change in blood glucose (derivative error), both adjusted for the recent glucose history. This algorithm is called the Fading Memory Proportional-Derivative (FMPD) Algorithm. The principal investigator of this study has published previous research regarding the use of this algorithm and found it to be well-suited to control blood glucose in type 1 diabetic animals. The addition of glucagon was helpful; better glycemic control with fewer glucose excursions were observed when small intermittent infusions of subcutaneous glucagon were given during times of impending low blood sugar (Ward et al. 2008).

Detailed description:
The objective of the current human study is to compare glycemic control in persons with Type 1 Diabetes using the FMPD Insulin plus Glucagon Delivery Algorithm vs. the FMPD Insulin-Alone Algorithm. Subjects will undergo two 28-hour sensor-augmented glycemic control studies. Each subject will be fitted with two short term continuous glucose monitoring systems and two subcutaneous (SC) infusion catheters. These catheters will allow for SC delivery of insulin and glucagon (or insulin plus a glucagon placebo). The accuracy of the wire sensors will be verified every 10 minutes with a venous blood glucose test. For the first 4 hours, the insulin and glucagon delivery will be controlled by venous blood in order to assess and compare the accuracy of the two sensors, after which the more accurate sensor (if it remains accurate) will control the FMPD algorithm. The main outcomes of our study are time spent in the target range (70 - 180 mg/dl) and the percentage of studies requiring intervention due to hypoglycemia (glucose \< 70 mg/dl). The accuracy of the sensors over the life of the study will also be evaluated.

The specific system used in this study of frequent blood testing and the use of two separate infusion pumps is not feasible for every day use for individuals with diabetes. However, if the glucose control algorithm (with or without the use of glucagon) provides effective blood glucose management over long time periods the calculation program may be integrated into a continuous blood glucose monitoring system with an insulin and glucagon pump.

Arms: arm 1: Glycemic control of subject participants was managed by the closed-loop system which delivered insulin and normal saline (instead of glucagon) as a placebo, based upon algorithm calculations. arm 2: Glycemic control of subject participants was managed by the system which delivered insulin and glucagon based upon algorithm calculations. arm 3: Pilot studies designed to assess safety of the system. Includes 6 participants undergoing 7 studies.
Interventions: intervention 1: Insulin, Asp(B28)- intervention 2: Glucagon intervention 3: Placebo
Intervention descriptions: intervention 1: Insulin dosing and frequency calculated by Fading Memory Proportional Derivative algorithm intervention 2: During incipient hypoglycemia, glucagon was given in an attempt to prevent overt hypoglycemia. Dosing and frequency was calculated by the Fading Memory Proportional Derivative algorithm intervention 3: Saline solution 0.9%

Protocol documents: