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

NCT ID: NCT00811317

Last Updated: 2017-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2009-10-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Closed-loop

Type 1 diabetic subjects under closed-loop blood glucose control

Group Type: EXPERIMENTAL

Closed-loop

Intervention Type: 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

Interventions

Closed-loop

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Boston University Charles River Campus

OTHER

Sponsor Role: lead

Responsible Party

Edward R. Damiano

Associate Professor of Biomedical Engineering

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven J Russell, M.D., Ph.D.

Role: STUDY_DIRECTOR

Massachusetts General Hospital

Edward Damiano, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Boston University

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17425438 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19888405 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20144330 (View on PubMed)

Other Identifiers

H-27207

Identifier Type: -

Identifier Source: secondary_id

SPID#0813

Identifier Type: -

Identifier Source: secondary_id

2007P-000101

Identifier Type: -

Identifier Source: org_study_id