Closed-loop Glucose Control for Automated Management of Type 1 Diabetes - Full Text View

Sponsor:	Boston University
Collaborators:	Massachusetts General Hospital Juvenile Diabetes Research Foundation
Information provided by:	Boston University
ClinicalTrials.gov Identifier:	NCT00811317

Purpose

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.

Condition	Intervention
Type 1 Diabetes	Device: Closed-loop device Device: Open-loop continuous sub-cutaneous infusion of insulin

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Closed-loop Glucose Control for Automated Management of Type 1 Diabetes

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Medicines Diabetes Type 1

Drug Information available for: Insulin Insulin beef Dextrose

U.S. FDA Resources

Further study details as provided by Boston University:

Primary Outcome Measures:

Average blood glucose over the closed-loop control period [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Fraction of time spent within each of several target glucose ranges: 70-125 mg/dl (fasted non-diabetic range) 70-199 mg/dl (random non-diabetic range) 70-99 mg/dl (fasted normal range) 70-139 mg/dl (random normal range) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Peak hyperglycemia following each meal [ Time Frame: After each of 3 meals ] [ Designated as safety issue: No ]
Duration of hyperglycemia > 180 after meals [ Time Frame: After each of 3 meals ] [ Designated as safety issue: No ]
Percentage of peak post-prandial hyperglycemias < 180 mg/dl (ADA target) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Amount of time spent with BG < 60 mg/dl [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
Number of hypoglycemic events and nadir BG for each [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
Amount of time spent with BG > 200 mg/dl [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Insulin doses around each meal and total insulin dose [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Amount of glucagon relative to insulin after each meal [ Time Frame: After each of 3 meals ] [ Designated as safety issue: No ]
Total glucagon dose [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
Blood glucagon levels and kinetics [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
Adequacy of our insulin dose scaling relative to subject weight [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Adequacy of the basal-rate of insulin infusion around idle times prior to individual meals [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Accuracy of the continuous glucose monitoring devices using blood glucose measurements as the standard. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Sensitivity for hypo- and hyperglycemia of the CGM devices using the BG measurements as the standard [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Accuracy data from the CGM devices will be used to estimate a safe set point using CGM data as the input to the closed-loop controller in combination with pre-clinical data from closed-loop experiments in diabetic pigs using CGM as the sensing limb [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Average glucose and glycemic variability during closed loop control in diabetic subjects compared to the comparable 24-hour period in non-diabetic subjects [ Time Frame: 24 hour ] [ Designated as safety issue: No ]
Average glucose and glycemic variability during the closed loop admission as compared to the comparable 24-hour period during the open-loop admission of diabetic subjects [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
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. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
Insulin and glucagon levels during the closed-loop and open-loop admissions of diabetic subjects compared to the comparable 24-hour period during the admission of non-diabetic subject [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

Enrollment:	38
Study Start Date:	May 2008
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Open-loop Type 1 diabetic subjects under open-loop (usual) control	Device: Open-loop continuous sub-cutaneous infusion of insulin Subject will regulate sub-cutaneous insulin infusion according to their usual practice and with their own insulin pump using information from self-monitoring blood glucose measurements
Experimental: Closed-loop Type 1 diabetic subjects under closed-loop blood glucose control	Device: Closed-loop device Computer algorithm developed by Firas El-Khatib and Edward Damiano at Boston University that controls sub-cutaneous infusion of insulin and glucagon to regulate blood glucose to target

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811317

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Boston University

Massachusetts General Hospital

Juvenile Diabetes Research Foundation

Investigators

Study Director:	Steven J Russell, M.D., Ph.D.	Massachusetts General Hospital
Principal Investigator:	Edward Damiano, Ph.D.	Boston University

More Information

Publications:

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.

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 Tech 9(2):135-44, 2007.

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 swine. J Diab Sci Technol 2009;3(4):789-803.

Responsible Party:	Edward Damiano, Boston University
ClinicalTrials.gov Identifier:	NCT00811317 History of Changes
Other Study ID Numbers:	2007P-000101, H-27207, SPID#0813
Study First Received:	May 29, 2008
Last Updated:	April 15, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Boston University:

diabetes
glucose
hyperglycemia
hypoglycemia
insulin
glucagon
counter-regulation
closed-loop

feedback
control
dual-infusion
subcutaneous
automated
artificial pancreas
intensive insulin therapy

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases

Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012