Three-day, In-clinic Evaluation of the BD 2nd Generation Continuous Glucose Sensor Device in Type 1 Diabetics

Three-day, In-clinic, Clamp Evaluation of the BD 2nd Generation Continuous Glucose Sensor in Subjects With Type 1 Diabetes

The purpose of this study is to investigate the accuracy and performance of a new subcutaneous continuous glucose monitor (BD-CGM, Becton Dickinson) in hyperglycemic (high blood sugar) and hypoglycemic (low blood sugar) "clamp" conditions and during meal excursions over the course of 72 hours as compared to a commercially available monitor.

This is a single site, non-randomized study. The study consists of a Screening Visit (Visit 1) during which the subject will be consented and the inclusion exclusion criteria confirmed. An interventional visit (Visit 2)which consists of a 72 hour in-clinic stay and a Follow-up Visit (Visit 3). Subjects eligible for the study will be admitted to the clinic for the Study Visit 2 in the afternoon on the day before the first Clamp is performed. An IV line for blood sampling will be established. One blood sample will be obtained for glucose determination and a second blood sample will be collected for immunoassay development before any sensors are inserted. Two BD-Glucose Binding Protein-Continuous Glucose Monitor Sensors(BD-GBP-CGM), with and without outer layer, and one commercial CGM sensor will be inserted in the subcutaneous tissue in the abdomen shortly thereafter. Blood sampling intervals will be adjusted over the 3 study days as determined by the study event (i.e. clamp period, meal excursion, nighttime). During the hyper- /hypo-glycemic clamps periods on Day 1 and Day 3 blood samples will be taken more frequently, every 5-10 minutes. During the breakfast meal on Day 2 sampling will occur at 10-15 minute intervals for 4 hours to capture the meal excursion. Sampling will be less frequent during the evening meal and at night during sleep hours.

Inclusion Criteria:

1. 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.

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

   1. Fasting glucose ≥ 7 mmol/L [126 mg/dL] - confirmed
   2. Two-hour OGTT (oral glucose tolerance test) glucose ≥ 11.1 mmol/L [200 mg/dL] - confirmed
   3. HbA1c ≥6.5% documented - confirmed
   4. Random glucose ≥ 11.1 mmol/L [200 mg/dL] with symptoms
   5. No data at diagnosis is available but the participant has a convincing history of hyperglycemia consistent with diabetes

3. 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

4. Signed informed consent

5. Age ≥18 and ≤65 years old

6. Body mass index between 19 and 35 kg/m2, inclusive

7. HbA1c ≤ 10.0%

Exclusion Criteria:

1. Uncontrolled arterial hypertension (diastolic blood pressure > 90 mm Hg and/or systolic blood pressure > 160 mm Hg)
2. Impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase ≥ three times the upper reference limit
3. Impaired renal function measured as creatinine > 1.2 times above the upper limit of normal
4. Diabetic ketoacidosis in the past 6 months
5. Severe hypoglycemia resulting in a seizure or loss of consciousness in the 6 months prior to enrollment
6. Conditions which may increase the risk of hypoglycemia or conditions of known microvascular (diabetic) complications will be assessed on an individual basis with exclusion based on the discretion of the principal investigator.
7. Current use of medications containing > 4000 mg acetaminophen per day.
8. Current use of MAO (monoamine oxidase) inhibitors.
9. Known allergy to eggs
10. Pregnancy, breast-feeding or intention of becoming pregnant
11. Current or recent alcohol or drug abuse by subject history.
12. Blood donation of more than 473 ml within the last 56 days
13. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
14. Any skin condition that prevents sensor placement on the abdomen (e.g., bad sunburn, pre-existing dermatitis, intertrigo, psoriasis, extensive scarring, cellulitis)
15. Known allergy to medical adhesives, e.g. Tegaderm
16. Hematocrit < 38% (males) and < 36% (females)
17. Potassium < 3.4 mmol/L
18. Active enrollment in another clinical trial