Closed Loop Glucose Control in a Simulated ICU Setting

Official title

Demonstration of an Expert Rule-Based Automated Insulin Delivery (AID) System for People With Type 1 and Type 2 Diabetes

Overview

This is a proof of concept safety study of a rule-based closed loop glucose control system designed for use in the intensive care unit setting. The persons with type 1 and type 2 diabetes in this study will have their glucose controlled to a range of 100-140 mg/dL by a fully autonomous novel rule-based closed loop glucose control system for a period of 24 hours. The subjects will consume three standardized meals and receive a continuous intravenous infusion of dextrose (D-glucose) during the 24 hour study period. Meals will not be announced to the glucose control system.

Detailed description

Tight glucose control in the intensive care unit (ICU) setting is difficult to achieve. The investigators hypothesize that a closed loop glucose control system that is rule-based will improve upon the glucose control currently achieved by the current open loop manual methods, and that this improved glucose control may improve the outcomes of critically ill patients.

This Earl Feasibility Study will test the ability of a prototype rule-based closed loop glucose control system named FUSION, to provide safe and effective glucose control in subjects with type 1 and type 2 diabetes in a clinical research center (CRC) setting. Subjects with type 1 diabetes have been chosen as safe and effective glucose control is difficult to achieve in these subjects during meal challenges. Subjects with type 2 diabetes have been chosen as they are insulin resistant, which makes their insulin resistance profile similar to that of ICU patients. As this is a safety study of a new medical device, the controlled environment of the CRC is preferable to the less controlled environment of an ICU setting.

The prototype FUSION system to be used in this study will consist to two Dexcom G6 continuous glucose monitors (CGM), the rule-based glucose control software run on an all-in-one medical computer, and two syringe pumps. The prototype system is housed on a medical cart. Based on the average glucose value of the two Dexcom G6 CGM's, and the algorithms of the FUSION systems rule-based glucose control software, the FUSION system will make rate adjustments every 5-10 minutes to the intravenous infusion rates of short acting insulin (NovoLog) and dextrose (D10NS) under its control, in an attempt to keep the subjects glucose in the range of 100-140 mg/dL. The FUSION system only requires entry of the subjects study identification number and weight in kilograms to initiate the system.

For safety reasons, the subjects will have their blood glucose independently measured every 10-60 minutes on the point of care Nova StatStrip system, throughout the 24 hour study period.

The study has halting criteria to avoid recurrent instances of severe hypoglycemia (\< 54 mg/dL).

The average of the two CGM's, that is used by the FUSION system for glucose control, will be used for statistical analysis.

Interventions

• Device FUSION closed loop glucose control system
  The FUSION system will be used to control the subjects glucose to a range of 100-140 mg/dL. Data will be collected for up to 24 hours, or upon early termination of the study session.

Primary outcome measures

• Primary Safety Measure [Time frame: From beginning of use of the FUSION System to end of use of the FUSION System, which will be a period of time up to 24 hours]
• Primary Efficacy Measure [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]

Secondary outcome measures (12)

• Percent of All Glucose Values Within Glucose Range <54 mg/dL [Time frame: From beginning of use of the FUSION System to end of use of the FUSION System, which will be a period of time of up to 24 hours]
• Percent of All Glucose Values Within Glucose Range 54-69 mg/dL [Time frame: From beginning of use of the FUSION System to end of use of the FUSION System, which will be a period of up to 24 hours.]
• Number of Hypoglycemic Events (<70 mg/dL) [Time frame: From beginning of use of the FUSION System until end of use of the FUSION System, which will be a period of time of up to 24 hours.]
• Percent of All Glucose Values Within Glucose Range 70-100 mg/dL [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]
• Percent of All Glucose Values Within Glucose Range 70-140 mg/dL [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]
• Percent of All Glucose Values Within Glucose Range 100-140 mg/dL [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]
• Percent of All Glucose Values Within Glucose Range >140 mg/dL [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]
• Percent of All Glucose Values Within Glucose Range >180 mg/dL [Time frame: From beginning of use of the FUSION System to end of use of the FUSION System, which will be a period of time of up to 24 hours]
• Percent of All Glucose Values Within Glucose Range >250 mg/dL [Time frame: From beginning of use of the FUSION System to end of use of the FUSION System, which will be a period of time of up to 24 hours]
• Average glucose value in mg/dL [Time frame: From beginning of use of the FUSION System to end of use of the FUSION System, which will be a period of time of up to 24 hours]
• Measure of dispersion - Coefficient of Variation [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]
• Clarke Error Grid Analysis of Continuous Glucose Monitor Data [Time frame: From beginning of use of FUSION System to end of use of FUSION System, which will be a period of time of up to 24 hours]

Eligibility criteria

Inclusion criteria

• Participants with type 1 and type 2 diabetes are eligible to be included in the study only if they meet all the following criteria:

• Are 18-70 years of age, inclusive.
• Can understand and sign an informed consent, communicate with the investigator, and understand and comply with the protocol requirements.
• Have had a diagnosis of type 1 or type 2 diabetes for a period of at least 3 months.
• Use insulin injections at home for glucose control.
• Have a hemoglobin A1c (HbA1c) in the range of 7.0 - 10.0%.
• Have a hemoglobin in the range for sex:

• Females: 7-15.5 grams/dL.
• Males: 7-17.5 grams/dl.
• Have adequate venous access sites in upper extremities.
• Body weight between 40 - 150 kg.

Exclusion criteria

• Have participated in an interventional medical, surgical, or pharmaceutical study within 30 days of screening.
• Have a known hypersensitivity to any of the components of study treatment.
• Have skin disease/injury at Dexcom G6 CGM insertion site(s) that would prevent insertion of the CGM.
• Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion would cause the individual to be noncompliant.
• Have a medical condition that in the opinion of the investigator could affect study participation and/or personal well-being.
• Have a clinically significant history or presence of any of the following conditions:

• Hepatic failure or has alanine aminotransferase (ALT) greater than 3 times the upper limit of normal.
• Has an estimated GFR <30 ml/min/1.73 m2 or End Stage Kidney Disease on renal replacement therapy.
• Have congestive heart failure greater than class 1 on the NYHA classification system.
• Have a history of seizures.
• Have a history of cerebrovascular accident.
• Have a history of ischemic heart disease.
• For female subjects of potential childbearing age (age 18 to 55) they will be excluded if:

• Pregnant.
• Refuse to agree to a pregnancy test at the time of enrollment.
• Have a positive urine pregnancy test at the time of enrollment.
• Have a positive Influenza or COVID test within 14 days of visit 3.
• Have any viral lower respiratory related symptoms (e.g., cough, chest tightness, respiratory distress) in the 14-day period prior to visit 3.
• Have a known unprotected Influenza or COVID exposure in the 14-day period prior to visit 3.
• Are currently being treated with Hydroxyurea, a medication which may cause the Dexcom G6 CGM to produce glucose readings that are higher than the actual glucose value.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Sardu C, D'Onofrio N, Balestrieri ML, Barbieri M, Rizzo MR, Messina V, Maggi P, Coppola N, Paolisso G, Marfella R. Outcomes in Patients With Hyperglycemia Affected by COVID-19: Can We Do More on Glycemic Control? Diabetes Care. 2020 Jul;43(7):1408-1415. doi: 10.2337/dc20-0723. Epub 2020 May 19. PMID 32430456
• DeJournett L. Essential elements of the native glucoregulatory system, which, if appreciated, may help improve the function of glucose controllers in the intensive care unit setting. J Diabetes Sci Technol. 2010 Jan 1;4(1):190-8. doi: 10.1177/193229681000400124. PMID 20167184
• DeJournett J, Nekludov M, DeJournett L, Wallin M. Performance of a closed-loop glucose control system, comprising a continuous glucose monitoring system and an AI-based controller in swine during severe hypo- and hyperglycemic provocations. J Clin Monit Comput. 2021 Apr;35(2):317-325. doi: 10.1007/s10877-020-00474-2. Epub 2020 Jan 31. PMID 32006145
• DeJournett J, DeJournett L. Comparative Simulation Study of Glucose Control Methods Designed for Use in the Intensive Care Unit Setting via a Novel Controller Scoring Metric. J Diabetes Sci Technol. 2017 Nov;11(6):1207-1217. doi: 10.1177/1932296817711297. Epub 2017 Jun 22. PMID 28637358
• DeJournett L, DeJournett J. In Silico Testing of an Artificial-Intelligence-Based Artificial Pancreas Designed for Use in the Intensive Care Unit Setting. J Diabetes Sci Technol. 2016 Nov 1;10(6):1360-1371. doi: 10.1177/1932296816653967. Print 2016 Nov. PMID 27301982

Identifiers

NCT: NCT07646067 · 2025P013846 · 5R44DK133084-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗