Effect of Gain on Closed-Loop Insulin

NCT02065895 | Completed Results

• 1 other identifier: 2012P-000401
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Keywords

Physiologic Insulin Delivery (PID); Closed Loop; Sensor; Insulin sensitivity

Outcome Measures

Primary Outcomes (1)

• Glucose Area Under the Curve (AUC) Breakfast

  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 Outcomes (1)

• Peak and Nadir Postprandial Glucose Concentration

  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 Outcomes (1)

• Nighttime Time-in-target 5.0-8.33mmol/l (Controller Set-point Plus and Minus 15 mg/dL)

  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

Study Arms (6)

HIGH error, LOW error, NO error

EXPERIMENTAL

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).

Device: HIGH error; Device: NO error; Device: LOW error

HIGH error, NO error, LOW error

EXPERIMENTAL

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).

Device: HIGH error; Device: NO error; Device: LOW error

NO error, HIGH error, LOW error

EXPERIMENTAL

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).

Device: HIGH error; Device: NO error; Device: LOW error

NO error, LOW error, HIGH error

EXPERIMENTAL

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).

Device: HIGH error; Device: NO error; Device: LOW error

LOW error, NO error, HIGH error

EXPERIMENTAL

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).

Device: HIGH error; Device: NO error; Device: LOW error

LOW error, HIGH error, NO error

EXPERIMENTAL

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),

Device: HIGH error; Device: NO error; Device: LOW error

Interventions

HIGH error DEVICE

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).

HIGH error, LOW error, NO error; HIGH error, NO error, LOW error; LOW error, HIGH error, NO error; LOW error, NO error, HIGH error; NO error, HIGH error, LOW error; NO error, LOW error, HIGH error

NO error DEVICE

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.

HIGH error, LOW error, NO error; HIGH error, NO error, LOW error; LOW error, HIGH error, NO error; LOW error, NO error, HIGH error; NO error, HIGH error, LOW error; NO error, LOW error, HIGH error

LOW error DEVICE

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).

HIGH error, LOW error, NO error; HIGH error, NO error, LOW error; LOW error, HIGH error, NO error; LOW error, NO error, HIGH error; NO error, HIGH error, LOW error; NO error, LOW error, HIGH error

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 %

You may not qualify if:

• 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

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (8)

• 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.

  PMID: 14741112 BACKGROUND

• 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.

  PMID: 14709197 BACKGROUND

• 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.

  PMID: 17130478 BACKGROUND

• 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.

  PMID: 18252903 BACKGROUND

• 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.

  PMID: 21367930 BACKGROUND

• 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.

  PMID: 22226251 BACKGROUND

• 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.

  PMID: 10905487 BACKGROUND

• 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.

  PMID: 16804068 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Medication Errors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Medical Errors; Health Services; Health Care Facilities Workforce and Services

Limitations and Caveats

In this study sensor calibration errors were simulated using a YSI reference glucose values; however, this may not fully capture errors that are due to delays between plasma and the interstitial fluid glucose value measured by a glucose sensor.

Results Point of Contact

• Title: Garry M. Steil, PhD
• Organization: Boston Children's Hospital

garry.steil@childrens.harvard.edu

617-355-7504

Study Officials

• Howard Wolpert, MD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 7, 2014
• First Posted: February 19, 2014
• Study Start: December 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 17, 2018
• Results First Posted: April 6, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)