A Clinical Study of the Performance of a Glucose Blinding Protein-Based Continuous Glucose Monitor (GBP CGM)

Development of accurate continuous glucose monitoring devices is critically important for
the maintenance of strict glycemic control without increasing the risk for hypoglycemia and
for the successful implementation of an artificial pancreas. Glucose binding protein-based
(GBP) continuous glucose monitors offer several potential advantages over commercially
available glucose oxidase based sensors. Unlike glucose oxidase based sensors, GBP sensors
do not require establishment of an equilibrium reduction/oxidation reaction and are not as
susceptible to interference from other compounds because they are engineered to recognize
only glucose. As a result, GBP-based glucose sensors are exceptionally accurate at low blood
glucose levels and have a faster warm-up time than glucose oxidase based systems. The
principal idea of this proposal is to evaluate the accuracy and performance of a second
generation glucose binding protein-based continuous glucose monitor (GBP CGM) developed by
BD Technologies in subjects with type 1 diabetes, with emphasis on warm-up period after
insertion, accuracy in hypoglycemic and hyperglycemic ranges, and lag time over a 24 hour
period of sensor use. In order to accomplish this, the investigators will conduct a clinical
trial consisting of 25.5-hour studies involving 15 subjects, each wearing one active and one
mock (no GBP) device simultaneously during meals and induced hypoglycemia to observe a wide
range of glucose values. The investigators envision that the glucose binding protein-based
continuous glucose monitor will demonstrate minimal warm-up time after insertion, overall
accuracy comparable to commercial glucose oxidase sensors with excellent performance in the
hypoglycemic range and a nominal lag time to sensing a change in blood glucose.

Inclusion Criteria:

- Clinical diagnosis of type 1 diabetes mellitus for ≥1 year. For an individual to be
enrolled at least one criterion from each list must be met.

- Criteria for documented hyperglycemia (at least 1 must be met):

1. Fasting glucose ≥126 mg/dL - confirmed

2. Two-hour oral Glucose Tolerance Tests (OGTT) glucose ≥200 mg/dL - confirmed

3. HbA1c ≥6.5% documented - confirmed

4. Random glucose ≥200 mg/dL with symptoms

5. No data at diagnosis is available but the participant has a convincing history
of hyperglycemia consistent with diabetes

- Criteria for requiring insulin at diagnosis (1 must be met):

1. Participant required insulin at diagnosis and continually thereafter

2. Participant did not start insulin at diagnosis but upon investigator review
likely needed insulin (significant hyperglycemia that did not respond to oral
agents) and did require insulin eventually and used continually

3. Participant did not start insulin at diagnosis but continued to be
hyperglycemic, had positive islet cell antibodies - consistent with latent
autoimmune diabetes in adults (LADA) and did require insulin eventually and used
continually

- Use of an insulin pump to treat his or her diabetes for at least six months prior to
the study.

- Actively using a bolus calculator function with the current insulin pump with
pre-defined parameters for glucose goal(s), carbohydrate ratio(s), and insulin
sensitivity factor(s).

- Signed informed consent

- Age ≥21 and <65 years old

- Body mass index between 19 and 30 kg/m2, inclusive

- HbA1c ≤11%

Exclusion Criteria:

- Uncontrolled arterial hypertension (diastolic blood pressure >90 mm Hg and/or
systolic blood pressure >160 mm Hg)

- Impaired hepatic function measured as alanine aminotransferase or aspartate
aminotransferase ≥three times the upper reference limit

- Impaired renal function measured as creatinine >1.2 times above the upper limit of
normal

- Diabetic ketoacidosis in the past 6 months

- Severe hypoglycemia resulting in a seizure or loss of consciousness in the 12 months
prior to enrollment

- Conditions which may increase the risk of induced hypoglycemia such as known coronary
artery disease, congestive heart failure, history of any cardiac disorder or
arrhythmia, history of a cerebrovascular event, history of migraines, seizure
disorder, syncope, adrenal insufficiency, or neurological disease.

- Current use of medications containing >4000 mg acetaminophen per day.

- Current use of L-Monoamine oxidases (MAO) inhibitors.

- Known microvascular (diabetic) complications (other than diabetic non-proliferative
retinopathy),such as history of laser coagulation, proliferative diabetic
retinopathy, known diabetic nephropathy (other than microalbuminuria with normal
creatinine) or neuropathy requiring treatment

- Known allergy to eggs

- Pregnancy, breast-feeding or intention of becoming pregnant

- Current or recent alcohol or drug abuse by patient history.