This is a scientific research study that will look at how a "closed-loop" system and the drug Pramlintide may work together to improve blood sugar control in people with type 1 diabetes mellitus. Pramlintide is approved by the Food and Drug Administration (FDA) and is given as an injection (subcutaneous) that works with insulin to lower blood sugar.
The objective of this study is to test whether standard pramlintide treatment plus a closed-loop insulin therapy is more efficacious in controlling glycemia than either of the individual therapies. The control algorithm is in effect an insulin dose calculator for mimicry of basal insulin secretion by estimating requirements for basal rates of insulin pump infusion based on current and past glucose levels estimated from the Continuous Glucose Monitor (CGM) device and prior insulin infusions. The closed-loop system-recommended insulin will replace (in a clinical setting) the basal rate insulin that the patient would normally use. The patients' meal insulin needs will be estimated using an insulin-to-carbohydrate ratio as per standard clinical practice and will be optimized prior to admission to the Clinical Research Unit. The primary goal of this feasibility study is to test the hypothesis that the combination of a closed loop system (Open-Loop Informed with a Model Predicted Control (MPC) algorithm plus a safety system module (SSM)) with pramlintide (a synthetic analog of the hormone amylin which in health is released by the β-cells along with insulin) treatment will improve glucose control versus each of the individual therapies. Because pramlintide reduces hyperglycemia extremes generated at meals and closed loop control markedly reduces the risk of hypoglycemia, thus representing potentially important complementary actions to reduced variability - the investigators expect to find decreased hyperglycemia while simultaneously decreasing hypoglycemia risks. Secondary goals are to explore factors associated with achieving safer and/or more effective closed loop control. For example, based upon our work in animal models, one secondary goal is to explore whether moderate inhibition of α-cell glucagon, known to occur with pramlintide administration in the early postprandial period, has the potential to repair inadequate glucagon counterregulation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Dose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily.
This visit will assess how well the closed loop system works without the pramlintide.
Dose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily.
University of Virginia, Center for Diabetes Technology
Charlottesville, Virginia, United States
Percent of Blood glucose tests within target range of 70 to 180 mg/dl
Percent of Blood glucose tests within target range of 70 to 180 mg/dl The primary outcome variable of glucose control within an American Diabetes Association (ADA) standard target range between 70 mg/dl to 180 mg/dl on a Yellow Springs Instrument (YSI) glucose analyzer. This is based upon the sample size estimate difference expected for % time within target range between artificial pancreas vs. patient control vs. Pramlintide plus artificial pancreas.
Time frame: 24 hours
Percent of Continuous Glucose Monitoring (CGM) System estimated blood glucose within target range of 70 to 180 mg/dl
A secondary analysis will be performed using the Continuous Glucose Monitoring \[CGM\] data estimated blood glucose within the American Diabetes Association \[ADA\] recommended target of 70-180 mg/dl.
Time frame: 72 hours
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