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

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Closed-loop
Sponsored by
Boston University Charles River Campus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring diabetes, glucose, hyperglycemia, hypoglycemia, insulin, glucagon, counter-regulation, closed-loop, feedback, control, dual-infusion, subcutaneous, automated, artificial pancreas, intensive insulin therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Closed-loop

Arm Description

Type 1 diabetic subjects under closed-loop blood glucose control

Outcomes

Primary Outcome Measures

Average Blood Glucose Over the Closed-loop Control Period

Secondary Outcome Measures

Percentage of Time Spent Within 70-180 mg/dl
Peak Hyperglycemia Following Each Meal
Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals
Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target)
Percentage of Time Spent With BG < 70 mg/dl
Number of Hypoglycemic Events
This outcome captures the number of hypoglycemic events that occurred throughout the entire study
Nadir Blood Glucose Level for Each Hypoglycemic Event
Percentage of Time Spent With BG > 180 mg/dl
Total Insulin Dose
Glucagon T-max
Time to maximum peak glucagon concentration
Total Glucagon Dose
Blood Glucagon Levels
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
Number of Carbohydrate Interventions
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals
Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard
Measuring the mean absolute relative difference (MARD) between the blood glucose measurement and CGM glucose readings, on three different CGM devices: Dexcom, Guardian and Navigator
Average Glucose and Glycemic Variability During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24 Hour Period in Non-diabetic Subjects
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
Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard
Mean absolute relative difference (MARD) of CGM and BG glucose readings in hypoglycemia (< 70 mg/dl) and hyperglycemia (>180 mg/dl) in three different CGM devices: Dexcom, Navigator and Guardian
Set Point Using CGM Data as the Input to the Controller for Future Studies
The algorithm in the Bionic Pancreas must have a pre-specified target glucose it is trying to achieve in order to make dosing decisions. Using data from this study, investigators planned to determine what an appropriate glucose target should be for future studies.
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

Full Information

First Posted
May 29, 2008
Last Updated
October 24, 2017
Sponsor
Boston University Charles River Campus
Collaborators
Massachusetts General Hospital, Juvenile Diabetes Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00811317
Brief Title
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Boston University Charles River Campus
Collaborators
Massachusetts General Hospital, Juvenile Diabetes Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Closed-loop
Arm Type
Experimental
Arm Description
Type 1 diabetic subjects under closed-loop blood glucose control
Intervention Type
Device
Intervention Name(s)
Closed-loop
Intervention Description
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
Primary Outcome Measure Information:
Title
Average Blood Glucose Over the Closed-loop Control Period
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Percentage of Time Spent Within 70-180 mg/dl
Time Frame
24 hours
Title
Peak Hyperglycemia Following Each Meal
Time Frame
After each of 3 meals
Title
Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals
Time Frame
After each of 3 meals
Title
Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target)
Time Frame
24 hours
Title
Percentage of Time Spent With BG < 70 mg/dl
Time Frame
24 hours
Title
Number of Hypoglycemic Events
Description
This outcome captures the number of hypoglycemic events that occurred throughout the entire study
Time Frame
24 hours
Title
Nadir Blood Glucose Level for Each Hypoglycemic Event
Time Frame
24 hours
Title
Percentage of Time Spent With BG > 180 mg/dl
Time Frame
24 hours
Title
Total Insulin Dose
Time Frame
24 hours
Title
Glucagon T-max
Description
Time to maximum peak glucagon concentration
Time Frame
24 hours
Title
Total Glucagon Dose
Time Frame
24 hours
Title
Blood Glucagon Levels
Time Frame
24 hours
Title
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
Title
Number of Carbohydrate Interventions
Time Frame
24 hours
Title
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing
Time Frame
24 hours
Title
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals
Time Frame
24 hours
Title
Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard
Description
Measuring the mean absolute relative difference (MARD) between the blood glucose measurement and CGM glucose readings, on three different CGM devices: Dexcom, Guardian and Navigator
Time Frame
24 hours
Title
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 hours
Title
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
Title
Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard
Description
Mean absolute relative difference (MARD) of CGM and BG glucose readings in hypoglycemia (< 70 mg/dl) and hyperglycemia (>180 mg/dl) in three different CGM devices: Dexcom, Navigator and Guardian
Time Frame
24 hours
Title
Set Point Using CGM Data as the Input to the Controller for Future Studies
Description
The algorithm in the Bionic Pancreas must have a pre-specified target glucose it is trying to achieve in order to make dosing decisions. Using data from this study, investigators planned to determine what an appropriate glucose target should be for future studies.
Time Frame
24 hours
Title
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
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven J Russell, M.D., Ph.D.
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Edward Damiano, Ph.D.
Organizational Affiliation
Boston University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
17425438
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.
Results Reference
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PubMed Identifier
19888405
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.
Results Reference
background
PubMed Identifier
20144330
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.
Results Reference
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Closed-loop Glucose Control for Automated Management of Type 1 Diabetes

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