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

Type 1 Diabetes Mellitus Clinical Trial

— SMA002  

Official title:

A Clinical Study of the Warm-Up, Accuracy, and Lag Performance of a Glucose Blinding Protein-Based Continuous Glucose Monitor (GBP CGM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01469715
• Other study ID #: 15696
• Status: Completed
• Phase: Phase 2
• First received: November 7, 2011
• Last updated: July 3, 2015
• Start date: November 2011
• Est. completion date: July 2012

Study information

• Verified date: July 2015
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the accuracy of the Becton Dickenson (BD) Technologies Glucose Binding Protein-Based Continuous Glucose Monitor (GBP CGM) in patients with Type 1 diabetes during low (goal glucose 55 mg/dL), normal (80-140 mg/dL) and high (>180mg/dL) glucose levels over a 24 hour period. This will be achieved by monitoring blood sugar levels when a regular dinner meal is given, when a liquid breakfast meal (BOOST Original containing 41 grams Carbohydrates (CHO), 4 grams fat, 10 grams protein) is given, when subcutaneous insulin is dosed to induce hypoglycemia to a goal of 55 mg/dL, and when a regular lunch meal is given. A Continuous Glucose Monitor (CGM) is an electronic device that measures and displays blood sugar (glucose) levels in the body throughout the day and night. The method being used to detect blood sugar in the investigational Glucose Binding Protein-Based Continuous Glucose Monitor (GBP CGM) is different than the method that is currently in use by commercially available models.

Some sensors cannot tell the difference between glucose (sugar) and other substances such as Tylenol, aspirin or citric acid etc. Because they cannot tell the difference, they may give false readings. The GBP CGM is made to only recognize glucose in the body rather than other substances (e.g., Tylenol, aspirin, citric acid, etc.). As a result, the investigators expect the new GBP CGM to be more accurate at detecting low blood sugar levels than the current devices.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Device:
• GBP CGM
Visit 1: Screening visit to determine if subject qualifies for the study. Visit 2: Inpatient admission requiring a 25.5-hour hospital stay. Each subject will wear one active & one mock device simultaneously during hyperglycemic & hypoglycemic challenge conditions to observe a wide range of glucose values. Visit 3 & 4: Subjects will return to the research center approximately 24 & 48 hours after sensor removal, respectively, for evaluation of the postimplantation sensor site. Visit 5: Subjects will return to the research center approximately 28 days post inpatient admission. Blood samples for future testing of GBP and polyethylene Glycol neutralizing antibodies will be taken at Visit 1 & 5.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
University of Virginia	Becton, Dickinson and Company, Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Relative Difference (ARD)	ARD=100*(G_sensor-G_reference)/G_reference; Calculated for when patient's G_ref was Normal (70-180 mg/dl), Hyperglycemic (>180 mg/dl) and Hypoglycemic (<70 mg/dl); The study data includes 208 paired sensor-YSI plasma glucose readings (G_reference) for each GBP CGM sensor (G_sensor) inserted for 24 hours during hyperglycemic and hypoglycemic challenge conditions. Data pairs will permit the detailed evaluation of sensor performance parameters, including static accuracy metrics such as median and mean absolute deviations and median and mean absolute relative deviation and Point CG-EGA, as well as dynamic parameters, such as warm-up time, trend accuracy (Rate CG-EGA), and sensor lag.	25.5 hours	No