Clinical trial NCT00811317: Closed-loop Glucose Control for Automated Management of Type 1 Diabetes
Official title: Closed-loop Glucose Control for Automated Management of Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: diabetes
glucose
hyperglycemia
hypoglycemia
insulin
glucagon
counter-regulation
closed-loop
feedback
control
dual-infusion
subcutaneous
automated
artificial pancreas
intensive insulin therapy
Lead sponsor: Boston University Charles River Campus
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: Juvenile Diabetes Research Foundation
First posted: 2008-12-18
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: We hypothesize that our integrated closed-loop glucose-control system can provide effective, tight, and safe blood glucose (BG) control in type 1 diabetes, thereby establishing the feasibility of closed-loop BG control.

Detailed description: This study investigates the utility of an integrated closed-loop glucose-control system for regulating BG in type 1 diabetic subjects. The closed-loop system utilizes sub-cutaneous infusion or insulin and glucagon under the control of a computer algorithm. The only inputs to the algorithm are the subject weight and BG values measured every five minutes. Subjects will undergo up to three 27 hour GCRC admissions during which they will consume three standardized meals. Subject may participate in up to two closed-loop visits (with different insulin lispro pharmacokinetic parameter settings in the control algorithm) and some subjects will participate in open-loop visits. During the closed-loop admission BG will be controlled by the closed-loop system. During the open-loop visit subjects will regulate their own BG in the usual function using their insulin pumps. A small group of non-diabetic subjects will undergo a single 27 hour GCRC admission during which they will eat the same standardized meals. During all admission BG will be measured every 5 minutes and blood will be collected for measurement of insulin and glucagon levels every 10 minutes. During the closed-loop admission of diabetic subjects and the single admission of non-diabetic subjects, three commercially available continuous glucose monitoring devices will be worn. The data from these devices will later be compared to reference BG data.

Eligibility criteria: Inclusion Criteria (type 1 diabetic subjects):

* Age 18 years or older
* Clinical type 1 diabetes for at least five years
* Otherwise healthy (mild chronic disease allowed if well controlled)
* Diabetes managed using an insulin infusion pump
* Body mass index (BMI) between 20 and 31
* Total daily dose (TDD) of insulin ≤ 1 U/kg and ≤ 100 U/day
* Post-prandial C-peptide \< 0.1 nmol/L at 90 minutes in a mixed meal (Sustacal) tolerance test by the DCCT method
* Hemoglobin A1c less than or equal to 8.5%
* Prescription medication regimen stable for at least 1 month

Inclusion Criteria (non-diabetic subjects):

* Age 18 years or older
* No personal history of diabetes, impaired fasting glucose, or impaired glucose tolerance
* No personal history of pancreatic disease
* Not taking medication that may affect glucose, insulin, or glucagon dynamics
* Otherwise healthy (mild chronic disease allowed if well controlled)
* Body mass index (BMI) between 20 and 31
* Normal 75 g oral glucose tolerance test (fasting, 1 hour, and 2 hour measurements)

Exclusion Criteria (all subjects):

* Unable to provide informed consent or are unable to comply with study procedures
* Current participation in another clinical trial
* Anemia (HCT or hemoglobin less than normal for sex)
* Elevated alanine aminotransferase (ALT \> 3 fold above upper limit of normal)
* Untreated or inadequately treated hyperthyroidism or hypothyroidism (abnormal TSH or free T4)
* Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception
* Progressive or proliferative diabetic retinopathy (subjects with mild, non-proliferative background retinopathy or stable disease previously treated with photocoagulation are not excluded).
* Renal insufficiency (creatinine clearance estimated by Cockcroft-Gault equation of ≤ 50 ml/min)
* Any known history or symptoms of coronary artery disease.
* Abnormal EKG
* Congestive heart failure
* History of TIA or stroke within preceding 6 months
* Acute illness or exacerbation of chronic illness at the time of the study procedure
* Change in medication regimen in the 30 days prior to enrollment
* History of seizures
* History of pheochromocytoma
* Abnormal plasma fractionated metanephrines
* History of adrenal disease or tumor
* History of pancreatic tumor, including insulinoma
* History of impaired gastric motility or gastroparesis requiring pharmacological or surgical treatment
* Current alcohol abuse (\> 3 drinks daily) or substance abuse (any use within the last 6 months of illegal drugs)
* Severe mental illness (schizophrenia, bipolar disease, inadequately treated depression, or any psychiatric hospitalization in the last year)
* Impaired cognition or altered mental status.
* Hypertension (blood pressure \> 140/90) at the time of screening
* Use of medications that reduce gastric motility
* Electrically powered implants that might be susceptible to RF interference
* Use non-insulin injectable anti-diabetic medications, inhaled insulin, or oral anti-diabetic medications
* History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
* Established history of latex, adhesive, tape allergy, inadequate venous access, history of allergy to or intolerance of aspirin.

Primary outcomes:
measure: Average Blood Glucose Over the Closed-loop Control Period
timeFrame: 24 hours
Secondary outcomes:
measure: Percentage of Time Spent Within 70-180 mg/dl
timeFrame: 24 hours
measure: Peak Hyperglycemia Following Each Meal
timeFrame: After each of 3 meals
measure: Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals
timeFrame: After each of 3 meals
measure: Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target)
timeFrame: 24 hours
measure: Percentage of Time Spent With BG < 70 mg/dl
timeFrame: 24 hours
measure: Number of Hypoglycemic Events
timeFrame: 24 hours
measure: Nadir Blood Glucose Level for Each Hypoglycemic Event
timeFrame: 24 hours
measure: Percentage of Time Spent With BG > 180 mg/dl
timeFrame: 24 hours
measure: Total Insulin Dose
timeFrame: 24 hours
measure: Glucagon T-max
timeFrame: 24 hours
measure: Total Glucagon Dose
timeFrame: 24 hours
measure: Blood Glucagon Levels
timeFrame: 24 hours
measure: Average Glucose and Glycemic Variability (MAGE) During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24-hour Period the Day Prior to Admission as Measured by Navigator CGM Data
timeFrame: 24 hours
measure: Number of Carbohydrate Interventions
timeFrame: 24 hours
measure: Number of Participants Achieving a Stable Glucose Response to Insulin Dosing
timeFrame: 24 hours
measure: Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals
timeFrame: 24 hours
measure: Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard
timeFrame: 24 hours
measure: Average Glucose and Glycemic Variability During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24 Hour Period in Non-diabetic Subjects
timeFrame: 24 hours
measure: Insulin and Glucagon Levels During the Closed-loop Admission as Compared to the Comparable 24 Hour Period During the Open Loop Admission of Diabetic Subjects
timeFrame: 24 hours
measure: Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard
timeFrame: 24 hours
measure: Set Point Using CGM Data as the Input to the Controller for Future Studies
timeFrame: 24 hours
measure: Insulin and Glucagon Levels During Closed Loop and Open Loop Admissions of Diabetic Subjects Compared to the Comparable 24 Hour Period During the Admission of Non-diabetic Subject
timeFrame: 24 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Russell, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Boston University
name: Edward Damiano, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: El-Khatib FH, Jiang J, Gerrity RG, Damiano ER. Pharmacodynamics and stability of subcutaneously infused glucagon in a type 1 diabetic Swine model in vivo. Diabetes Technol Ther. 2007 Apr;9(2):135-44. doi: 10.1089/dia.2006.0006.
citation: El-Khatib FH, Jiang J, Damiano ER. Adaptive closed-loop control provides blood-glucose regulation using dual subcutaneous insulin and glucagon infusion in diabetic Swine. J Diabetes Sci Technol. 2007 Mar;1(2):181-92. doi: 10.1177/193229680700100208.
citation: El-Khatib FH, Jiang J, Damiano ER. A feasibility study of bihormonal closed-loop blood glucose control using dual subcutaneous infusion of insulin and glucagon in ambulatory diabetic swine. J Diabetes Sci Technol. 2009 Jul 1;3(4):789-803. doi: 10.1177/193229680900300428.