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Trial record 11 of 1022 for:    Area Under Curve AND insulin

Effect of Gain on Closed-Loop Insulin

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ClinicalTrials.gov Identifier: NCT02065895
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : April 6, 2018
Last Update Posted : May 17, 2018
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Joslin Diabetes Center

Tracking Information
First Submitted Date  ICMJE February 7, 2014
First Posted Date  ICMJE February 19, 2014
Results First Submitted Date  ICMJE August 23, 2017
Results First Posted Date  ICMJE April 6, 2018
Last Update Posted Date May 17, 2018
Study Start Date  ICMJE December 2013
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2018)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: February 14, 2014)
Glucose Area Under the Curve (AUC) Breakfast [ Time Frame: 8:00 AM to 12:00 PM with samples obtained every 10-15 minutes ]
Breakfast closed loop control (artificial pancreas). Closed-loop control calculates insulin delivery based on a minute to minute glucose signal, typically obtained from a glucose sensor. In this study, the sensor signal is replaced by a gold-standard laboratory standard (YSI) glucose value and three different controller configurations are evaluated. Low AUC is generally preferred.
Change History Complete list of historical versions of study NCT02065895 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2018)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2014)
Peak and Nadir Postprandial Glucose Concentration [ Time Frame: 8: 00 AM to 12:00 PM ]
Incidence of supplemental carbohydrate (15 grams of juice) used to prevent or correct hypoglycemia (glucose less than 60 mg/dL)
Current Other Pre-specified Outcome Measures
 (submitted: April 5, 2018)
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.
Original Other Pre-specified Outcome Measures
 (submitted: February 14, 2014)
Nighttime time-in-target (controller set-point plus and minus 15 mg/dL) [ Time Frame: 12:00 AM - 8:00 AM ]
Nighttime incidence of supplemental carbohydrate used to prevent or correct blood glucose less than 60 mg/dL. Fasting glucose (8 AM value).
 
Descriptive Information
Brief Title  ICMJE Effect of Gain on Closed-Loop Insulin
Official Title  ICMJE Effect of Gain on Closed-Loop Insulin
Brief Summary

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.

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:

  1. to assess the fasting glucose levels achieved as the overall closed-loop gain and effective target is increased or decreased, and
  2. determine the system's ability to produce an acceptable breakfast meal response under these conditions
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Study subjects are studied under closed-loop control on three occasions: once with the glucose values used for control equal to blood glucose (NO error), once with values 33% higher than blood glucose (HIGH error), and once with values 20% lower than blood glucose (LOW error). The six different sequences of these three exposures then comprise the six arms of this crossover study.
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE
  • Device: 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).
  • Device: NO error
    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.
  • Device: 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 0.8 times the true glucose value (analogous to lower gain higher target).
Study Arms  ICMJE
  • 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).
    Interventions:
    • Device: HIGH error
    • Device: NO error
    • Device: LOW error
  • 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).
    Interventions:
    • Device: HIGH error
    • Device: NO error
    • Device: LOW error
  • 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).
    Interventions:
    • Device: HIGH error
    • Device: NO error
    • Device: LOW error
  • 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).
    Interventions:
    • Device: HIGH error
    • Device: NO error
    • Device: LOW error
  • 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).
    Interventions:
    • Device: HIGH error
    • Device: NO error
    • Device: LOW error
  • 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),
    Interventions:
    • Device: HIGH error
    • Device: NO error
    • Device: LOW error
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 25, 2017)
8
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2014)
12
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02065895
Other Study ID Numbers  ICMJE 2012P-000401
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Joslin Diabetes Center
Study Sponsor  ICMJE Joslin Diabetes Center
Collaborators  ICMJE Juvenile Diabetes Research Foundation
Investigators  ICMJE
Principal Investigator: Howard Wolpert, MD Joslin Diabetes Center
PRS Account Joslin Diabetes Center
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP