Controlled Insulin Delivery: Combining Technology With Treatment

Early Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Device: Closed-loop session

• Registration Number: NCT01484457
• Lead Sponsor: Sansum Diabetes Research Institute

Brief Summary

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.

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.

Study Timeline

• Study Start: 2008-07
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Study First Submitted: 2011-11-15
• Study First Submitted QC: 2011-11-30
• Study First Posted: 2011-12-02
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-18
• Last Update Posted: 2021-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Closed-loop control system	Closed-loop session	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: 1. restoring euglycemia (80-140 mg/dL) when the controller is initiated during a period when the subject's glucose is above the euglycemic range; 2. restoring euglycemia (80-140 mg/dL) when the controller is challenged with a small unannounced meal (\~25 g CHO).

Primary Outcome Measures

Name	Time	Method
Restoration of Euglycemia	12 hours	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. The patients will be followed for the duration of the 12 hour study.

Secondary Outcome Measures

Name	Time	Method
Average percent-of-time-in-range (80 - 180 mg/dL)	12 hours	All reported blood glucose values per both CGM and YSI ware analyzed for average percent-of-time-in-range (80 - 180 mg/dL). The participants will be followed for the duration of the 12 hour study.

Trial Locations

Locations (2)

Sansum Diabetes Research Institute; 🇺🇸 Santa Barbara, California, United States

Schneider Children's Medical Center of Israel; 🇮🇱 Petah Tikva, Israel