Closed Loop Glucose Control in Patients With Type 1 and Type 2 Diabetes

Demonstration of an Artificial Intelligence Based Closed Loop Glucose Control System as a Therapeutic Modality in Type 1 and Type 2 Diabetic Patients

This is a proof of concept safety study of an artificial intelligence based closed loop glucose control system designed for use in the intensive care unit setting.

The type 1 and type 2 diabetic subjects in this study will have their glucose controlled to a range of 100-140 mg/dL by a novel artificial intelligence based closed loop glucose control system for a period of 24 hours. The subjects will consume three standardized meals during the 24 hour study period.

Tight glucose control in the intensive care unit (ICU) setting is difficult to achieve. The investigators hypothesize that a closed loop glucose control system based on artificial intelligence (AI) 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, including those with COVID-19.

This Earl Feasibility Study will test the ability of a prototype artificial intelligence 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 the first in human 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 AI-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 rules of the FUSION systems AI-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.

Inclusion Criteria:

1. Are 18-70 years of age, inclusive.

2. Can understand and sign an informed consent, communicate with the investigator, and understand and comply with the protocol requirements.

3. Have had a diagnosis of type 1 or type 2 diabetes for a period of at least 1 year.

4. Use insulin injections at home for glucose control and are on a stable insulin regimen without more than a 20% change in their total daily insulin dose during the previous 3 months. Their total daily insulin dose during the previous 3 months will be confirmed through a review of the subject's electronic health record, insulin prescriptions, and insulin pump settings (if applicable).

5. Have a hemoglobin A1c (HbA1c) in the range of 7.0 - 10.0%.

6. Have a hemoglobin in the normal range for sex:

   1. Females: 12-15.5 grams/dL.
   2. Males: 13.5-17.5 grams/dl.

7. Have adequate venous access sites in upper extremities.

8. Body weight between 40 - 150 kg.

Exclusion Criteria:

1. Have participated in an interventional medical, surgical, or pharmaceutical study within 30 days of screening.

2. Have a known hypersensitivity to any of the components of study treatment.

3. Have skin disease/injury at Dexcom G6 CGM insertion site(s) that would prevent insertion of the CGM.

4. Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion would cause the individual to be noncompliant.

5. Have a medical condition that in the opinion of the investigator could affect study participation and/or personal well-being.

6. Have a clinically significant history or presence of any of the following conditions:

   1. Hepatic failure or has alanine aminotransferase (ALT) greater than 3 times the upper limit of normal.
   2. Has an estimated glomerular filtration rate (GFR) <60 ml/min/1.73 m2 or End Stage Kidney Disease on renal replacement therapy.
   3. Type 2 diabetic subjects who have a C-peptide level less than 0.2 nmol/L (these subjects will be referred to their primary care doctor or endocrinologist for further work up).
   4. Have congestive heart failure of class 1 or greater on the New York Heart Association (NYHA) classification system.
   5. Have a history of seizures.
   6. Have a history of cerebrovascular accident.
   7. Have a history of ischemic heart disease.

7. For female subjects of potential childbearing age (age 18 to 55) they will be excluded if:

   1. Pregnant.
   2. Refuse to agree to a pregnancy test at the time of enrollment.
   3. Have a positive urine pregnancy test at the time of enrollment.

8. Have a positive COVID-19 test within 14 days of visit 3.

9. Have any COVID-19 related symptoms in the 14-day period prior to visit 3.

10. Have a known unprotected COVID-19 exposure in the 14-day period prior to visit 3.