Sensor-Augmented Insulin Delivery: Insulin Plus Glucagon Versus Insulin Alone
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Insulin, Asp(B28)-; Glucagon; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Insulin dosing and frequency calculated by Fading Memory Proportional Derivative algorithm; 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; Saline solution 0.9%
Other intervention name(s): Aspart insulin; Novolog; Glucagen; Normal saline, NaCl 0.9%
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Glucagon
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: diabetes; pancreas; beta cell; glucagon; insulin; hypoglycemia