- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02065895
Effect of Gain on Closed-Loop Insulin
The purpose of this study is to test the ability of an advanced external Physiologic Insulin Delivery (ePID) algorithm (a step by step process used to develop a solution to a problem) to get acceptable meal responses over a range of gain. Gain is defined as how much insulin is given in response to a change in a patient's glucose level.
This study also examines the effectiveness of the external Physiologic Insulin Delivery (ePID) closed-loop insulin delivery computer software. The investigators would like to assess whether fasting target levels can be achieved as the closed-loop gain increases or decreases, and to evaluate the system's ability to produce an acceptable breakfast meal response.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
There have been significant advances in diabetes management technology, including more sophisticated insulin pumps and more accurate real-time continuous glucose monitors. The next technological development is widely thought to be the introduction of an algorithm linking the pump and sensor to form a closed-loop insulin delivery system. The algorithm used for this purpose needs to be robust to changes in an individual's insulin sensitivity, and the sensor's sensitivity to glucose. Insulin sensitivity (how much the patient's glucose level changes in response to a change in insulin delivery) and algorithm gain (how much insulin is delivered in response to a change in glucose) determine the systems overall closed-loop gain. Ideally, the overall gain can be set to achieve the lowest possible peak postprandial glucose response without postprandial hypoglycemia. However, if the algorithm's gain is set to a fixed value and the subject's insulin sensitivity changes, the overall-gain will change. Some degradation in closed-loop performance might be acceptable during periods whenever the subject's insulin sensitivity is low (i.e., the subject is insulin resistant) and the risk of hypoglycemia may actually be reduced. However, if the subject becomes more sensitive the system may become less stable and the risk of postprandial hypoglycemia may increase. In addition to changes in insulin sensitivity, glucose sensors will sometimes over- or under-read blood glucose as sensor sensitivity increases or decreases. This will result in a change in the closed-loop algorithm's effective target. The purpose of this study is to evaluate the ability of an advanced Physiologic Insulin Delivery algorithm to achieve an acceptable breakfast response as the gain and effective target glucose level changes. Specifically:
- to assess the fasting glucose levels achieved as the overall closed-loop gain and effective target is increased or decreased, and
- determine the system's ability to produce an acceptable breakfast meal response under these conditions
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Joslin Diabetes Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Type 1 diabetes for > 3 years
- Manage diabetes using a continuous glucose monitor and continuous subcutaneous insulin infusion pump
- Non obese (BMI < 30)
- Aged 18 - 75 years old
- HbA1c < 8 %
Exclusion Criteria:
- renal or hepatic failure
- cancer or lymphoma
- Malabsorption or malnourishment
- Hypercortisolism
- Alcoholism or drug abuse
- Anemia (hematocrit < 36 in females and <40 in males)
- Eating disorder
- Dietary restrictions
- Acetaminophen allergy
- Chronic acetaminophen use
- Glucocorticoid therapy
- History of gastroparesis
- Use of Beta blockers
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HIGH error, LOW error, NO error
Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control higher than blood glucose (HIGH error), then second with glucose-value-used-for-control lower than blood glucose (LOW error), then third with glucose-value-used-for-control equal blood glucose (NO error).
|
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
|
Experimental: HIGH error, NO error, LOW error
Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control higher than blood glucose (HIGH error), then second with glucose-value-used-for-control equal blood glucose (NO error), then third with glucose-value-used-for-control lower than blood glucose (LOW error).
|
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
|
Experimental: NO error, HIGH error, LOW error
Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control equal blood glucose (NO error), then second with glucose-values-used-for-control higher than blood glucose (HIGH error), then third with glucose-value-used-for-control lower than blood glucose (LOW error).
|
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
|
Experimental: NO error, LOW error, HIGH error
Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control equal blood glucose (NO error), then second with glucose-value-used-for-control lower than blood glucose (LOW error), then third with glucose-value-used-for-control higher than blood glucose (HIGH error).
|
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
|
Experimental: LOW error, NO error, HIGH error
Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with with glucose-value-used-for-control lower than blood glucose (LOW error), then second with glucose-value-used-for-control equal blood glucose (NO error), then third with glucose-value-used-for-control higher than blood glucose (HIGH error).
|
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
|
Experimental: LOW error, HIGH error, NO error
Subjects were randomized to receive overnight and breakfast closed-loop glucose control glucose on three occasions: first with glucose-value-used-for-control lower than blood glucose (LOW error), then second with glucose-value-used-for-control equal blood glucose (NO error), then third glucose-value-used-for-control higher than blood glucose (HIGH error),
|
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 1.33 times the true glucose value (analogous to higher gain lower target).
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL and glucose-value-used-for-control equal to the true glucose value.
Overnight and breakfast closed-loop control were performed using a target glucose of 120 mg/dL but with the glucose-value-used-for-control equal to 0.8 times the true glucose value (analogous to lower gain higher target).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Glucose Area Under the Curve (AUC) Breakfast
Time Frame: On day #1, day #2 and day #3 (each day could be 24 hours to 7 days apart from prior one, and completed within 6 week period) 8:00 AM to 2:00 PM on day following admission, with samples obtained every 10-15 minutes, for each sequence of calibration errors
|
Glucose Area Under the Curve (AUC) Breakfast defines the total exposure to glucose during breakfast.
Breakfast is typically considered the most difficult meal to control; low AUC is desirable.This outcome measure was analyzed for each of the three calibration error values (high error, no error and low error).
|
On day #1, day #2 and day #3 (each day could be 24 hours to 7 days apart from prior one, and completed within 6 week period) 8:00 AM to 2:00 PM on day following admission, with samples obtained every 10-15 minutes, for each sequence of calibration errors
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Peak and Nadir Postprandial Glucose Concentration
Time Frame: On day #1, day #2 and day #3 (each day could be 24 hours to 7 days apart from prior one, and completed within 6 week period) 8:00 AM to 12:00 PM on day following admission, with samples obtained every 10-15 minutes, for each sequence of calibration errors
|
Highest and lowest glucose concentrations obtained during breakfast meal.
|
On day #1, day #2 and day #3 (each day could be 24 hours to 7 days apart from prior one, and completed within 6 week period) 8:00 AM to 12:00 PM on day following admission, with samples obtained every 10-15 minutes, for each sequence of calibration errors
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Nighttime Time-in-target 5.0-8.33mmol/l (Controller Set-point Plus and Minus 15 mg/dL)
Time Frame: On day #1, day #2 and day #3 (each day could be 24 hours to 7 days apart from prior one, and completed within 6 week period) 12:00 AM to 6:00 AM on day following admission, with samples obtained every 10-15 minutes, for each sequence of calibration errors
|
Night-time in target range 5.0-8.33,
following the 3 hour controller initialization period blood glucose remained at or near target.
|
On day #1, day #2 and day #3 (each day could be 24 hours to 7 days apart from prior one, and completed within 6 week period) 12:00 AM to 6:00 AM on day following admission, with samples obtained every 10-15 minutes, for each sequence of calibration errors
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Howard Wolpert, MD, Joslin Diabetes Center
Publications and helpful links
General Publications
- Steil GM, Panteleon AE, Rebrin K. Closed-loop insulin delivery-the path to physiological glucose control. Adv Drug Deliv Rev. 2004 Feb 10;56(2):125-44. doi: 10.1016/j.addr.2003.08.011.
- Steil GM, Rebrin K, Janowski R, Darwin C, Saad MF. Modeling beta-cell insulin secretion--implications for closed-loop glucose homeostasis. Diabetes Technol Ther. 2003;5(6):953-64. doi: 10.1089/152091503322640999.
- Steil GM, Rebrin K, Darwin C, Hariri F, Saad MF. Feasibility of automating insulin delivery for the treatment of type 1 diabetes. Diabetes. 2006 Dec;55(12):3344-50. doi: 10.2337/db06-0419.
- Weinzimer SA, Steil GM, Swan KL, Dziura J, Kurtz N, Tamborlane WV. Fully automated closed-loop insulin delivery versus semiautomated hybrid control in pediatric patients with type 1 diabetes using an artificial pancreas. Diabetes Care. 2008 May;31(5):934-9. doi: 10.2337/dc07-1967. Epub 2008 Feb 5.
- Steil GM, Palerm CC, Kurtz N, Voskanyan G, Roy A, Paz S, Kandeel FR. The effect of insulin feedback on closed loop glucose control. J Clin Endocrinol Metab. 2011 May;96(5):1402-8. doi: 10.1210/jc.2010-2578. Epub 2011 Mar 2.
- Loutseiko M, Voskanyan G, Keenan DB, Steil GM. Closed-loop insulin delivery utilizing pole placement to compensate for delays in subcutaneous insulin delivery. J Diabetes Sci Technol. 2011 Nov 1;5(6):1342-51. doi: 10.1177/193229681100500605.
- Buchanan TA, Xiang AH, Peters RK, Kjos SL, Berkowitz K, Marroquin A, Goico J, Ochoa C, Azen SP. Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes. Diabetes. 2000 May;49(5):782-8. doi: 10.2337/diabetes.49.5.782.
- Panteleon AE, Loutseiko M, Steil GM, Rebrin K. Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system. Diabetes. 2006 Jul;55(7):1995-2000. doi: 10.2337/db05-1346.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2012P-000401
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 1 Diabetes
-
Poznan University of Medical SciencesUnknownDiabetes Mellitus Type 1 | Remission of Type 1 Diabetes | Chronic Complications of DiabetesPoland
-
Eledon PharmaceuticalsWithdrawnBrittle Type 1 Diabetes MellitusUnited States
-
National Institute of Allergy and Infectious Diseases...PPD; Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN)CompletedType 1 Diabetes Mellitus | T1DM | T1D | New-onset Type 1 Diabetes MellitusUnited States, Australia
-
Hoffmann-La RocheCompletedType 2 Diabetes, Type 1 DiabetesAustria, United Kingdom
-
Shanghai Changzheng HospitalRecruitingBrittle Type 1 Diabetes MellitusChina
-
Capillary Biomedical, Inc.TerminatedType 1 Diabetes | Type 1 Diabetes Mellitus | Diabetes Mellitus, Type I | Diabetes Mellitus, Insulin-Dependent, 1 | IDDMAustria
-
Capillary Biomedical, Inc.CompletedDiabetes Mellitus, Type 1 | Type 1 Diabetes | Type 1 Diabetes Mellitus | Diabetes Mellitus, Insulin-Dependent, 1Australia
-
AstraZenecaCompletedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
NYU Langone HealthNational Heart, Lung, and Blood Institute (NHLBI)Recruiting
-
Rabin Medical CenterDreaMed DiabetesTerminated
Clinical Trials on HIGH error
-
Shirley Ryan AbilityLabU.S. Department of EducationCompleted
-
Shirley Ryan AbilityLabRecruitingStroke | Cerebral Vascular Accident (CVA)/StrokeUnited States
-
Stanford UniversityThe University of Texas Health Science Center, Houston; University of California... and other collaboratorsCompletedLearning | Adaptive Expertise | Error Management TrainingUnited States
-
McGill UniversityCanadian Institutes of Health Research (CIHR); Centre for Interdisciplinary... and other collaboratorsNot yet recruitingCognitive Impairment | Stroke, Ischemic | Stroke Hemorrhagic
-
VA Office of Research and DevelopmentCompleted
-
VA Office of Research and DevelopmentRecruitingDiabetes Mellitus | Peripheral Artery Disease | Transtibial AmputationUnited States
-
European Georges Pompidou HospitalUnknownEmbolism | Pulmonary Embolism | Pulmonary Vascular Disorder | Pulmonary Embolism and Thrombosis | Diagnostic ErrorsFrance
-
University of HaifaTel Aviv University; Ben-Gurion University of the NegevCompleted
-
University of California, San DiegoActive, not recruitingAnorexia NervosaUnited States
-
Universitaire Ziekenhuizen KU LeuvenKU Leuven; Bioxtreme Ltd.Completed