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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00811317
First Posted: December 18, 2008
Last Update Posted: October 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Massachusetts General Hospital
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Edward R. Damiano, Boston University
  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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Closed-loop Glucose Control for Automated Management of Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Edward R. Damiano, Boston University:

Primary Outcome Measures:
  • Average Blood Glucose Over the Closed-loop Control Period [ Time Frame: 24 hours ]

Secondary Outcome Measures:
  • Percentage of Time Spent Within 70-180 mg/dl [ Time Frame: 24 hours ]
  • Peak Hyperglycemia Following Each Meal [ Time Frame: After each of 3 meals ]
  • Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals [ Time Frame: After each of 3 meals ]
  • Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target) [ Time Frame: 24 hours ]
  • Percentage of Time Spent With BG < 70 mg/dl [ Time Frame: 24 hours ]
  • Number of Hypoglycemic Events [ Time Frame: 24 hours ]
    This outcome captures the number of hypoglycemic events that occurred throughout the entire study

  • Nadir Blood Glucose Level for Each Hypoglycemic Event [ Time Frame: 24 hours ]
  • Percentage of Time Spent With BG > 180 mg/dl [ Time Frame: 24 hours ]
  • Total Insulin Dose [ Time Frame: 24 hours ]
  • Glucagon T-max [ Time Frame: 24 hours ]
    Time to maximum peak glucagon concentration

  • Total Glucagon Dose [ Time Frame: 24 hours ]
  • Blood Glucagon Levels [ Time Frame: 24 hours ]
  • 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 ]
  • Number of Carbohydrate Interventions [ Time Frame: 24 hours ]
  • Number of Participants Achieving a Stable Glucose Response to Insulin Dosing [ Time Frame: 24 hours ]
  • Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals [ Time Frame: 24 hours ]
  • Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard [ Time Frame: 24 hours ]
    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 [ Time Frame: 24 hours ]
  • 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 ]
  • Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard [ Time Frame: 24 hours ]
    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 [ Time Frame: 24 hours ]
    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 [ Time Frame: 24 hours ]

Enrollment: 11
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
Experimental: Closed-loop
Type 1 diabetic subjects under closed-loop blood glucose control
Device: 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

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00811317


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Boston University Charles River Campus
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:
Responsible Party: Edward R. Damiano, Associate Professor of Biomedical Engineering, Boston University
ClinicalTrials.gov Identifier: NCT00811317     History of Changes
Other Study ID Numbers: 2007P-000101
H-27207
SPID#0813
First Submitted: May 29, 2008
First Posted: December 18, 2008
Results First Submitted: April 18, 2017
Results First Posted: October 25, 2017
Last Update Posted: October 25, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Edward R. Damiano, 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