Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Conditions
Keywords
Closed Loop Glucose Control, Artificial Pancreas, Artificial Intelligence, Glucose, Intensive Care Unit
Brief summary
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.
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 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.
Interventions
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.
Sponsors
Emory University
Ideal Medical Technologies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Early feasibility safety study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Outcome | 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 | Percent of All Glucose Values Within Glucose Range \< 70 mg/dL |
| Primary Efficacy Outcome | 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 70-180 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of All Glucose Values Within Glucose Range > 180 mg/dL | 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 | Percentage of all glucose values that are greater than 180 mg/dL |
| Percent of All Glucose Values Within Glucose Range > 250 mg/dL | 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 | The percentage of all glucose values that are greater than 250 mg/dL |
| Percent Coefficient of Variation of Glucose | 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 | The percent coefficient of variation of glucose will be calculated by dividing the standard deviation of the average glucose value in mg/dL by the average glucose value in mg/dL, then multiplying this value by 100 |
| Weight in Kilograms | 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 weight in kilograms of the subjects |
| Average Glucose Value in mg/dL | 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 | The average of all measured glucose values in mg/dL |
| Total Daily Dose of Insulin in Units/Kilogram | As measured prior to the start of the closed loop glucose control session | The subjects total daily dose of insulin used prior to the start of the closed loop glucose control session was calculated by adding up all of the insulin doses used by the subjects (both short and long acting insulin) in units and dividing this value by the subjects weight in Kilograms |
| Hemoglobin A1c Percentage Level | As measured within 2 weeks of the start of the closed loop glucose control session | The subjects hemoglobin A1c measurement from a blood draw taken within 2 weeks of the start of the closed loop glucose control session |
| C-Peptide Level in ng/mL | As measured from a blood draw taken within 2 weeks of the start of the closed loop glucose control session | C-Peptide level as measured from a blood draw |
| Body Mass Index | As measured at the start of the closed loop glucose control session | The body mass index was calculated by dividing the subjects weight in kilograms by their height in meters squared |
| Percent of All Glucose Values Within Glucose Range < 54 mg/dL | 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 | The percentage of all glucose values that less than 54 mg/dL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FUSION Closed Loop Glucose Control System Safety Study All subjects will be treated with the FUSION closed loop glucose control system for up to 24 hours
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. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | FUSION Closed Loop Glucose Control System Safety Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 52.4 Years STANDARD_DEVIATION 7.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 1 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Primary Efficacy Outcome
Percent of All Glucose Values Within Glucose Range 70-180 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Primary Efficacy Outcome | 79.0 Percentage of all glucose values | Standard Deviation 21.3 |
Primary
Primary Safety Outcome
Percent of All Glucose Values Within Glucose Range \< 70 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 up to 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Primary Safety Outcome | 1.4 Percentage of all glucose values | Standard Deviation 2.7 |
Secondary
Average Glucose Value in mg/dL
The average of all measured glucose values 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Average Glucose Value in mg/dL | 148.4 mg/dL | Standard Deviation 25.1 |
Secondary
Body Mass Index
The body mass index was calculated by dividing the subjects weight in kilograms by their height in meters squared
Time frame: As measured at the start of the closed loop glucose control session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Body Mass Index | 31.0 Kilograms/Height in meters squared | Standard Deviation 6.1 |
Secondary
C-Peptide Level in ng/mL
C-Peptide level as measured from a blood draw
Time frame: As measured from a blood draw taken within 2 weeks of the start of the closed loop glucose control session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | C-Peptide Level in ng/mL | 1.5 ng/mL | Standard Deviation 1.5 |
Secondary
Hemoglobin A1c Percentage Level
The subjects hemoglobin A1c measurement from a blood draw taken within 2 weeks of the start of the closed loop glucose control session
Time frame: As measured within 2 weeks of the start of the closed loop glucose control session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Hemoglobin A1c Percentage Level | 8.5 Percentage of glycated hemoglobin | Standard Deviation 0.8 |
Secondary
Percent Coefficient of Variation of Glucose
The percent coefficient of variation of glucose will be calculated by dividing the standard deviation of the average glucose value in mg/dL by the average glucose value in mg/dL, then multiplying this value by 100
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Percent Coefficient of Variation of Glucose | 21.3 Percentage of Coefficient of Variation | Standard Deviation 5.3 |
Secondary
Percent of All Glucose Values Within Glucose Range > 180 mg/dL
Percentage of all glucose values that are greater than 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Percent of All Glucose Values Within Glucose Range > 180 mg/dL | 19.6 Percentage of all glucose values | Standard Deviation 22 |
Secondary
Percent of All Glucose Values Within Glucose Range > 250 mg/dL
The percentage of all glucose values that are greater than 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Percent of All Glucose Values Within Glucose Range > 250 mg/dL | 2.9 Percentage of all glucose values | Standard Deviation 4.4 |
Secondary
Percent of All Glucose Values Within Glucose Range < 54 mg/dL
The percentage of all glucose values that less than 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Percent of All Glucose Values Within Glucose Range < 54 mg/dL | 0 Percentage of all glucose values | Standard Deviation 0 |
Secondary
Total Daily Dose of Insulin in Units/Kilogram
The subjects total daily dose of insulin used prior to the start of the closed loop glucose control session was calculated by adding up all of the insulin doses used by the subjects (both short and long acting insulin) in units and dividing this value by the subjects weight in Kilograms
Time frame: As measured prior to the start of the closed loop glucose control session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Total Daily Dose of Insulin in Units/Kilogram | 0.9 Units Insulin/Kilogram per day | Standard Deviation 0.4 |
Secondary
Weight in Kilograms
Average weight in kilograms of the subjects
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FUSION Closed Loop Glucose Control System Safety Study | Weight in Kilograms | 88.2 Kilograms | Standard Deviation 14.7 |