Controlled Insulin Delivery: Combining Technology With Treatment

This study has been completed.

Sponsor:

Collaborators:

Juvenile Diabetes Research Foundation

Schneider Children's Medical Center, Israel

Information provided by (Responsible Party):

Lois Jovanovic, MD, Sansum Diabetes Research Institute

ClinicalTrials.gov Identifier:

NCT01484457

First received: November 15, 2011

Last updated: June 5, 2012

Last verified: June 2012

History of Changes

Purpose

Hypothesis: Closed-loop control systems for an artificial pancreas using multi-parametric model predictive control can be developed and evaluated safely in patients with Type 1 Diabetes Mellitus (T1DM) to control blood glucose concentrations.

This study seeks to combine real-time continuous glucose sensing with automated insulin delivery in a closed-loop system that will achieve euglycemia in patients with T1DM. The end result of this line of research will be an artificial pancreas that will provide around-the-clock glucose regulation through controlled insulin delivery in response to detected patterns of change in glucose levels.

Condition	Intervention	Phase
Diabetes Mellitus, Type 1	Device: Closed-loop session	Phase 0

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Controlled Insulin Delivery: Combining Technology With Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: type 1 diabetes

MedlinePlus related topics: Blood Sugar Diabetes Diabetes Medicines Diabetes Type 1

Drug Information available for: Pancreatin Insulin human Pancrelipase

U.S. FDA Resources

Further study details as provided by Sansum Diabetes Research Institute:

Primary Outcome Measures:

Restoration of Euglycemia [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
The primary endpoint of this pilot study is successful restoration of euglycemia from the two perturbed conditions using closed loop control with minimal hypo- and hyperglycemia exposure. The first condition involves restoration of euglycemia when the subject is in a hyperglycemic state. The second condition involves restoration of euglycemia following consumption of a meal containing 25g CHO with no insulin bolus.

Secondary Outcome Measures:

Average percent-of-time-in-range (80 - 180 mg/dL) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
All reported blood glucose values per both CGM and YSI ware analyzed for average percent-of-time-in-range (80 - 180 mg/dL).

Enrollment:	19
Study Start Date:	July 2008
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Closed-loop control system The objective of this study is to automate glucose control in subjects with type 1 diabetes using a computer control algorithm in a controlled in-clinic research setting. The controller will be evaluated under two conditions: restoring euglycemia (80-140 mg/dL) when the controller is initiated during a period when the subject's glucose is above the euglycemic range; restoring euglycemia (80-140 mg/dL) when the controller is challenged with a small unannounced meal (~25 g CHO).	Device: Closed-loop session Subjects will arrive fasting at 7am unless needed for hypoglycemia (glucose < 70 mg/dL) and no extra bolus insulin after 3am. An IV catheter will be inserted for blood samples and for IV administration of glucose if necessary. Blood samples will be analyzed for glucose by YSI 2300Stat every 30 minutes. Breakfast consisting of 25g of CHO will be eaten at 7:30 am and the subject will bolus for this amount of CHO. The controller is switched "on" on the down slope of the meal response, and the subject is brought to a basal steady-state by the controller. Target blood glucose is 110 ± 30-mg/dL. After approximately 3 hours a small lunch will be eaten consisting of 25g of CHO (unannounced meal challenge). The subject will be monitored until blood glucose returns to euglycemia. Other Name: Closed-loop Artificial Pancreas Device

Arms

Assigned Interventions

Experimental: Closed-loop control system

The objective of this study is to automate glucose control in subjects with type 1 diabetes using a computer control algorithm in a controlled in-clinic research setting.

The controller will be evaluated under two conditions:

restoring euglycemia (80-140 mg/dL) when the controller is initiated during a period when the subject's glucose is above the euglycemic range;
restoring euglycemia (80-140 mg/dL) when the controller is challenged with a small unannounced meal (~25 g CHO).

Device: Closed-loop session

Subjects will arrive fasting at 7am unless needed for hypoglycemia (glucose < 70 mg/dL) and no extra bolus insulin after 3am. An IV catheter will be inserted for blood samples and for IV administration of glucose if necessary. Blood samples will be analyzed for glucose by YSI 2300Stat every 30 minutes.

Breakfast consisting of 25g of CHO will be eaten at 7:30 am and the subject will bolus for this amount of CHO. The controller is switched "on" on the down slope of the meal response, and the subject is brought to a basal steady-state by the controller. Target blood glucose is 110 ± 30-mg/dL.

After approximately 3 hours a small lunch will be eaten consisting of 25g of CHO (unannounced meal challenge). The subject will be monitored until blood glucose returns to euglycemia.

Other Name: Closed-loop Artificial Pancreas Device

Detailed Description:

The goal of the JDRF Artificial Pancreas Project is to produce an autonomous artificial pancreas that can safely and effectively regulate glycemia in people with type 1 diabetes mellitus. In our work, this fully automated closed-loop system combines a subcutaneous continuous glucose monitor (CGM) and a continuous subcutaneous insulin infusion (CSII) pump with a sophisticated control algorithm. This is a proof-of-concept study to demonstrate that the controller could bring the patient back to a relatively normal glucose concentration after an unannounced meal and from mild hyperglycemia. Once the system is initiated, all insulin delivery is calculated automatically. There was no outside intervention either by the subject or medical personnel. An artificial pancreas system that aims at replicating normal beta-cell function by using the subcutaneous-subcutaneous (sc-sc) route needs to address inherent delays in both glucose sensing and insulin delivery. Our strategic approach is that a closed-loop system should operate safely without any knowledge of meals or other disturbances. We have developed the Artificial Pancreas System (APS©) and used it to clinically evaluate a control strategy that allows efficient glycemic control without any a priori meal information. The Artificial Pancreas device uses the Artificial Pancreas System (APS©) platform with the OmniPod insulin pump, the DexCom SEVEN PLUS CGM and a multi-parametric model predictive control algorithm (mpMPC) with an insulin-on-board (IOB) safety constraint.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Willing to sign the consent form
Type 1 diabetes for at least 1 year prior to the study
Using continuous subcutaneous insulin infusion pump
Above 21 years of age
Willing to follow the study requirements

Exclusion Criteria:

Allergy to the sensor or to one of its components
Psychiatric disorders
Reported diabetic ketoacidosis within last 3 months
Abnormal liver function (Transaminase > 2 times the upper limit of normal)
Heart failure
Any carcinogenic disease
Any other chronic abnormality
Unwilling to perform or to follow the research protocol
Participation in any other study concurrent with the proposed study
Creatinine concentration above the upper limit of normal for age and sex
Active coronary artery disease
Active gastroparesis
History of uncontrolled seizures
Pregnancy
Untreated adrenal insufficiency
Hypokalemia
Uncontrolled thyroid disease.
Condition, which in the opinion of the investigator, would interfere with patient safety

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01484457

Locations

United States, California
Sansum Diabetes Research Institute
Santa Barbara, California, United States, 93105
Israel
Schneider Children's Medical Center of Israel
Petah Tikva, Israel

Sponsors and Collaborators

Sansum Diabetes Research Institute

Juvenile Diabetes Research Foundation

Schneider Children's Medical Center, Israel

Investigators

Principal Investigator:

Lois Jovanovic, M.D.

Sansum Diabetes Research Institute

More Information

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Dua P, Doyle FJ 3rd, Pistikopoulos EN. Model-based blood glucose control for Type 1 diabetes via parametric programming. IEEE Trans Biomed Eng. 2006 Aug;53(8):1478-91.

Garg S, Zisser H, Schwartz S, Bailey T, Kaplan R, Ellis S, Jovanovic L. Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: a randomized controlled trial. Diabetes Care. 2006 Jan;29(1):44-50.

Hovorka R, Chassin LJ, Wilinska ME, Canonico V, Akwi JA, Federici MO, Massi-Benedetti M, Hutzli I, Zaugg C, Kaufmann H, Both M, Vering T, Schaller HC, Schaupp L, Bodenlenz M, Pieber TR. Closing the loop: the adicol experience. Diabetes Technol Ther. 2004 Jun;6(3):307-18.

Hovorka R, Shojaee-Moradie F, Carroll PV, Chassin LJ, Gowrie IJ, Jackson NC, Tudor RS, Umpleby AM, Jones RH. Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT. Am J Physiol Endocrinol Metab. 2002 May;282(5):E992-1007.

Jeha GS, Karaviti LP, Anderson B, Smith EO, Donaldson S, McGirk TS, Haymond MW. Insulin pump therapy in preschool children with type 1 diabetes mellitus improves glycemic control and decreases glucose excursions and the risk of hypoglycemia. Diabetes Technol Ther. 2005 Dec;7(6):876-84.

Jones SM, Quarry JL, Caldwell-McMillan M, Mauger DT, Gabbay RA. Optimal insulin pump dosing and postprandial glycemia following a pizza meal using the continuous glucose monitoring system. Diabetes Technol Ther. 2005 Apr;7(2):233-40.

Jovanovic L. Role of diet and insulin treatment of diabetes in pregnancy. Clin Obstet Gynecol. 2000 Mar;43(1):46-55. Review. No abstract available.

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Palerm CC, Zisser H, Bevier WC, Jovanovic L, Doyle FJ 3rd. Prandial insulin dosing using run-to-run control: application of clinical data and medical expertise to define a suitable performance metric. Diabetes Care. 2007 May;30(5):1131-6. Epub 2007 Feb 15.

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Shimoda S, Nishida K, Sakakida M, Konno Y, Ichinose K, Uehara M, Nowak T, Shichiri M. Closed-loop subcutaneous insulin infusion algorithm with a short-acting insulin analog for long-term clinical application of a wearable artificial endocrine pancreas. Front Med Biol Eng. 1997;8(3):197-211.

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Zisser H, Jovanovic L, Doyle F 3rd, Ospina P, Owens C. Run-to-run control of meal-related insulin dosing. Diabetes Technol Ther. 2005 Feb;7(1):48-57.

Zisser H, Robinson L, Bevier W, Dassau E, Ellingsen C, Doyle FJ, Jovanovic L. Bolus calculator: a review of four "smart" insulin pumps. Diabetes Technol Ther. 2008 Dec;10(6):441-4. Review.

Zisser HC, Bevier WC, Jovanovic L. Restoring euglycemia in the basal state using continuous glucose monitoring in subjects with type 1 diabetes mellitus. Diabetes Technol Ther. 2007 Dec;9(6):509-15.

Responsible Party:	Lois Jovanovic, MD, CEO and Chief Scientific Officer, Sansum Diabetes Research Institute
ClinicalTrials.gov Identifier:	NCT01484457 History of Changes
Other Study ID Numbers:	JDRF 22-2009-796
Study First Received:	November 15, 2011
Last Updated:	June 5, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Sansum Diabetes Research Institute:

Diabetes Mellitus
Closed Loop
Artificial Pancreas

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

Insulin
Pancrelipase
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

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