Effect of Gain on Closed-Loop Insulin
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      The purpose of this study is to test the ability of an advanced external Physiologic Insulin
      Delivery (ePID) algorithm (a step by step process used to develop a solution to a problem) to
      get acceptable meal responses over a range of gain. Gain is defined as how much insulin is
      given in response to a change in a patient's glucose level.

      This study also examines the effectiveness of the external Physiologic Insulin Delivery
      (ePID) closed-loop insulin delivery computer software. The investigators would like to assess
      whether fasting target levels can be achieved as the closed-loop gain increases or decreases,
      and to evaluate the system's ability to produce an acceptable breakfast meal response.
    

Detailed description: 
      There have been significant advances in diabetes management technology, including more
      sophisticated insulin pumps and more accurate real-time continuous glucose monitors. The next
      technological development is widely thought to be the introduction of an algorithm linking
      the pump and sensor to form a closed-loop insulin delivery system. The algorithm used for
      this purpose needs to be robust to changes in an individual's insulin sensitivity, and the
      sensor's sensitivity to glucose. Insulin sensitivity (how much the patient's glucose level
      changes in response to a change in insulin delivery) and algorithm gain (how much insulin is
      delivered in response to a change in glucose) determine the systems overall closed-loop gain.
      Ideally, the overall gain can be set to achieve the lowest possible peak postprandial glucose
      response without postprandial hypoglycemia. However, if the algorithm's gain is set to a
      fixed value and the subject's insulin sensitivity changes, the overall-gain will change. Some
      degradation in closed-loop performance might be acceptable during periods whenever the
      subject's insulin sensitivity is low (i.e., the subject is insulin resistant) and the risk of
      hypoglycemia may actually be reduced. However, if the subject becomes more sensitive the
      system may become less stable and the risk of postprandial hypoglycemia may increase. In
      addition to changes in insulin sensitivity, glucose sensors will sometimes over- or
      under-read blood glucose as sensor sensitivity increases or decreases. This will result in a
      change in the closed-loop algorithm's effective target. The purpose of this study is to
      evaluate the ability of an advanced Physiologic Insulin Delivery algorithm to achieve an
      acceptable breakfast response as the gain and effective target glucose level changes.
      Specifically:

        1. to assess the fasting glucose levels achieved as the overall closed-loop gain and
           effective target is increased or decreased, and

        2. determine the system's ability to produce an acceptable breakfast meal response under
           these conditions
    

Intervention name(s): HIGH error; NO error; LOW error
Intervention type(s): Device; Device; Device
Intervention description(s): Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).; Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.; Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Study subjects are studied under closed-loop control on three occasions: once with the glucose values used for control equal to blood glucose (NO error), once with values 33% higher than blood glucose (HIGH error), and once with values 20% lower than blood glucose (LOW error). The six different sequences of these three exposures then comprise the six arms of this crossover study.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Physiologic Insulin Delivery (PID); Closed Loop; Sensor; Insulin sensitivity