Demonstration of an Artificial Intelligence Based Closed Loop Glucose Control System as a Therapeutic Modality in Type 2 Diabetic Patients
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Sponsor: Ideal Medical Technologies

 
DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP 
GLUCOSE CONTROL SYSTEM AS A THERAPEUTIC MODALITY IN TYPE 2 
DIABETIC PATIENTS 
NCT Number: 05386849 
Principal Investigator: Dr. Francisco Pasquel 
April 12, 2022 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP 
GLUCOSE CONTROL SYSTEM AS A THERAPEUTIC MODALITY IN TYPE 2 
DIABETIC PATIENTS 
Protocol Number: IMT 2022-1 
National Clinical Trial Identified Number:  NA 
Principal Investigator: Dr. Francisco Pasquel 
Sponsor: Ideal Medical Technologies 
Sponsor Contact: Dr. Leon DeJournett 
Funded by: Ideal Medical Technologies 
Version Number:  1.0.4 
25 March 2022 
 
 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Explanation 
of glucose 
control 
software 
(Page 20) 
1. Removed reference to fuzzy logic. 
2. Added improved explanation around 
fact that the FUSION devices glucose 
control software is an expert based 
rule system, or knowledge based 
system. 
 
1. The FUSION system does not use 
fuzzy logic. 
2. To better describe the basis for how 
the FUSION systems glucose control 
software works. 
Halting 
Criteria (Page 
57) 
1. Addition of diabetic ketoacidosis. 
2. Addition of glucose < 70 mg/dL 
requiring assistance to recover from. 
3. Addition of any unanticipated 
adverse device effect (UADE). 
 
1. To protect subjects if device cannot 
prevent development of diabetic 
ketoacidosis. 
2. To protect subjects who develop 
hypoglycemia that requires 
assistance to recover from. 
3. To protect subjects from harmful 
device effects. 
Discharge 
criteria 
1. Added steps to be taken when 
subject removed for hypoglycemia. 
 
1. To better describe for the study 
nurse the monitoring that needs to 

NIH-FDA Phase 2 and 3 IND/IDE Clinical Trial Protocol Template   
(Protocol 2, 
pages 93-94) 
2. Added steps to be taken when 
subject removed for diabetic 
ketoacidosis. 
occur when subject removed from 
study for hypoglycemia. 
2. To better describe for the study 
nurse the monitoring that needs to 
occur when subject removed from 
study for diabetic ketoacidosis. 
 
Frequency of 
Reference 
Glucose 
Values 
(Protocol 2, 
pages 88-89) 
1. Clarified how often Reference 
Glucose Values will be obtained 
under different circumstances. 
1. To clarify for study personnel how 
often Reference Glucose Values will 
be obtained, including every 10 
minute checks when the Dexcom 
G6 CGM is less than 80 mg/dL. 
Frequency of 
Reference 
Glucose 
Values 
(Protocol 2, 
pages 88-89) 
1. Added criteria to screen for diabetic 
ketoacidosis if the Reference or 
Dexcom G6 CGM(s) have been 
greater than 200 mg/dL for more 
than one hour consecutively. 
1. To screen for diabetic ketoacidosis 
if the subject is experiencing 
persistent hyperglycemia. 
Screening 
prior to 
initiation 
closed loop 
glucose 
control 
session (Time 
0 to 5 hours, 
page 47). 
1. Added screening criteria to make 
sure subjects are not in DKA before 
entering the study, and to also make 
sure they are not acutely ill with any 
other illness, prior to starting the 
study. 
 
1. To prevent using the FUSION 
system on an acutely ill or 
unstable subject. 
Use of device 
(Protocol 2, 
page 88) 
1. Added instructions to mitigate 
against risk of introducing an 
electrostatic discharge to the FUSION 
system. 
1. To prevent an electrostatic 
discharge from adversely affecting 
the performance of the FUSION 
system. 
Length of use 
of medication 
syringes 
(time 5 to 29 
hours, page 
49) 
1. Added instructions to not use the 
medication syringes for a period of 
time exceeding 24 hours. 
1. To avoid using the medication 
syringes for a period of time 
exceeding 24 hours, as the 
biocompatibility of the medications 
in the syringes is unclear for a 
period of time exceeding 24 hours, 
and is thus not FDA approved. 

NIH-FDA Phase 2 and 3 IND/IDE Clinical Trial Protocol Template   
Necessary 
equipment 
(time 0 to 2 
hours, Pages 
46-47) 
1. Specified equipment to be on hand 
in the CRC, including cardiac 
monitor, pulse oximeter, blood 
pressure cuff, and resuscitation cart. 
1. To make sure CRC has adequate 
equipment on hand to both 
monitor and resuscitate the 
subject. 
Synopsis 
(page 4) 
1. Decreased study size from five type 1 
and five type 2 diabetic subjects to 
two type 2 diabetic subjects. 
1. To minimize the number of subjects 
exposed to a high risk device being 
used in humans for the first time. 
Type 2 diabetic subjects chosen as 
they are less likely to develop 
hypoglycemia. 
Labs (page 6) 
1. Added hemoglobin to screening labs 
1. To exclude subjects who do not 
have normal hemoglobin levels, 
given that the study subjects may 
have up to 80 mL of blood drawn 
during the course of the study. 
Rescue 
Medication 
(Page 53) 
1. Added Glucagon 
1. To give additional option for 
treatment of hypoglycemia. 
Meal Plan 
1. Changed closed loop control session 
start time to 1200 with first meal 
being lunch 
1. To allow CGM’s time to warm up 
and verify their accuracy, prior to 
starting the study 
Entire 
Document 
1. Changed length of study to 31 hours 
2. Changed interval for checking 
Reference Glucose Values to every 
10-60 minutes 
3. Changed document version year to 
2022 to reflect year submitted to 
IRB 
1. To ensure consistency within the 
document 
2. To ensure consistency within the 
document, and to cover all 
possible intervals between 
Reference Glucose Values 
3. To update document to coincide 
with year of submission to IRB 
Protocol 1 
(Page 87-88) 
1. Changed carrier solution for FUSION 
systems insulin and dextrose 
infusions from normal saline to ½ 
normal saline 
1. To reflect agreement with FDA to 
use a hypo-osmotic carrier 
solution to minimize risk of vein 
irritation from infusion of hyper-
osmolar D10 normal saline 
solution used by the FUSION 
system 

NIH-FDA Phase 2 and 3 IND/IDE Clinical Trial Protocol Template   
Meal 
Challenge 
Protocol 
(Page 95) 
1. Changed discharge criteria from 
four consecutive Reference Glucose 
Values in range of 80-200 mg/dL to 
four consecutive Reference Glucose 
Values in range of 80-250 mg/dL 
1. To facilitate discharge of subjects 
whose glucose levels are within 
their normal range seen at home 
Study Data 
Identification 
(Pages 76-77) 
1. Clarified that only de-identified 
data will be used in the study 
1. To ensure protection of the study 
subjects and any study subject 
data obtained through the 
subject’s participation in the 
study 
Role of IMT 
Personnel 
(Page 77) 
1. Clarified role IMT personnel will 
have in the study – limited to use of 
the FUSION system with no study 
subject interaction, no provision of 
study subject medical care, and no 
extraction or analysis of the study 
data 
1. To prevent IMT personnel from 
becoming involved in study 
subject medical care and to 
protect the integrity of the 
studies data for purposes of 
future regulatory submissions 

  
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 5 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 6 
2 
INTRODUCTION ............................................................................................................................................ 7 
2.1 
Study Rationale- Glycemic Control in the ICU ................................................................................ 7 
2.2 
Study rationale – COVID-19............................................................................................................. 11 
2.3 
Study rationale – Fusion AI based artificial pancreas system .................................................... 21 
3 
fusion system testing Background ............................................................................................................. 21 
3.1 
Risk/Benefit Assessment .................................................................................................................. 35 
3.1.1 
Known Potential Risks ................................................................................................... 35 
3.1.2 
Known Potential Benefits .............................................................................................. 36 
3.1.3 
Assessment of Potential Risks and benefits .............................................................. 36 
4 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 40 
5 
STUDY DESIGN ........................................................................................................................................... 42 
5.1 
Overall Design .................................................................................................................................... 42 
5.2 
Scientific Rationale for Study Design.............................................................................................. 43 
5.3 
Justification for Dose ......................................................................................................................... 43 
5.4 
End of Study Definition ..................................................................................................................... 43 
6 
STUDY POPULATION ................................................................................................................................ 43 
6.1 
Inclusion Criteria ................................................................................................................................ 43 
6.2 
Exclusion Criteria ............................................................................................................................... 44 
6.3 
Lifestyle Considerations .................................................................................................................... 45 
6.4 
Screen Failures .................................................................................................................................. 45 
6.5 
Strategies for Recruitment and Retention ...................................................................................... 45 
7 
STUDY INTERVENTION ............................................................................................................................ 46 
7.1 
Study Intervention(s) Administration ............................................................................................... 46 
7.1.1 
Study Intervention Description ..................................................................................... 46 
7.1.2 
Dosing and Administration ............................................................................................ 52 
7.2 
Preparation/Handling/Storage/Accountability ................................................................................ 52 
7.2.1 
Acquisition and accountability ...................................................................................... 52 
7.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 52 
7.2.3 
Product Storage and Stability ....................................................................................... 53 
7.2.4 
Preparation ...................................................................................................................... 53 
7.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 54 
7.4 
Study Intervention Compliance ........................................................................................................ 54 
7.5 
Concomitant Therapy ........................................................................................................................ 54 
7.5.1 
Rescue Medicine ............................................................................................................ 54 
8 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 55 
8.1 
Discontinuation of Study Intervention ............................................................................................. 55 
8.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 55 
8.3 
Lost to Follow-Up ............................................................................................................................... 56 
9 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 56 
9.1 
Efficacy Assessments ....................................................................................................................... 56 

  
9.2 
Safety and Other Assessments ....................................................................................................... 57 
9.2.1 
Safety 
 .......................................................................................................................... 57 
9.2.2 
Halting criteria ................................................................................................................. 58 
9.2.3 
Physical exam/Labs ....................................................................................................... 58 
9.2.4 
Special assays ................................................................................................................ 59 
9.2.5 
Use of Existing Medical Record Data ......................................................................... 59 
9.3 
Adverse Events and Serious Adverse Events ............................................................................... 59 
9.3.1 
Definition of Adverse Events (AE) ............................................................................... 59 
9.3.2 
Definition of Serious Adverse Events (SAE) .............................................................. 60 
9.3.3 
Classification of an Adverse Event .............................................................................. 60 
9.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 62 
9.3.5 
Adverse Event Reporting .............................................................................................. 62 
9.3.6 
Serious Adverse Event Reporting ............................................................................... 62 
9.3.7 
Reporting Events to Participants ................................................................................. 63 
9.3.8 
Events of Special Interest ............................................................................................. 63 
9.3.9 
Reporting of Pregnancy ................................................................................................ 63 
9.4 
Unanticipated Problems .................................................................................................................... 63 
9.4.1 
Definition of Unanticipated Problems (UP) ................................................................. 63 
9.4.2 
Unanticipated Problem Reporting ................................................................................ 64 
9.4.3 
Reporting Unanticipated Problems to Participants ................................................... 64 
10 
STATISTICAL CONSIDERATIONS .......................................................................................................... 65 
10.1 
Statistical Measurements ................................................................................................................. 65 
10.2 
Sample Size Determination .............................................................................................................. 67 
10.3 
Populations for Analyses .................................................................................................................. 67 
10.4 
Statistical Analyses............................................................................................................................ 67 
10.4.1 
General Approach .......................................................................................................... 67 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 67 
10.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 68 
10.4.4 
Safety Analyses .............................................................................................................. 68 
10.4.5 
Baseline Descriptive Statistics ..................................................................................... 69 
10.4.6 
Planned Interim Analyses ............................................................................................. 69 
10.4.7 
Sub-Group Analyses ..................................................................................................... 69 
10.4.8 
Tabulation of Individual participant Data .................................................................... 69 
10.4.9 
Exploratory Analyses ..................................................................................................... 69 
11 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 69 
11.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 69 
11.1.1 
Informed Consent Process ........................................................................................... 69 
11.1.2 
Study Discontinuation and Closure ............................................................................. 70 
11.1.3 
Confidentiality and Privacy ........................................................................................... 71 
11.1.4 
Future Use of Stored Specimens and Data ............................................................... 72 
11.1.5 
Key Roles and Study Governance .............................................................................. 72 
11.1.6 
Safety Oversight ............................................................................................................. 73 
11.1.7 
Clinical Monitoring .......................................................................................................... 73 
11.1.8 
Quality Assurance and Quality Control ....................................................................... 74 
11.1.9 
Data Handling and Record Keeping ............................................................................ 74 
11.1.10 
Protocol Deviations ........................................................................................................ 75 
11.1.11 
Publication and Data Sharing Policy ........................................................................... 75 

  
11.1.12 
Conflict of Interest Policy .............................................................................................. 76 
11.2 
Additional Considerations ................................................................................................................. 77 
11.3 
Abbreviations ...................................................................................................................................... 78 
11.4 
Protocol Amendment History ........................................................................................................... 80 
12 
REFERENCES ............................................................................................................................................. 81 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
1 
STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation (ICH) 
Good Clinical Practice (GCP) and the following:  
 
• 
Applicable standards as set forth by the NIH and/or FDA. 
 
National Institute of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED 
LOOP GLUCOSE CONTROL SYSTEM AS A THERAPEUTIC MODALITY IN 
TYPE 2 DIABETIC PATIENTS 
Study Description: 
Tight glucose control in the Intensive Care Unit (ICU) setting is difficult to 
achieve. We hypothesize that a closed loop glucose control system based 
on artificial intelligence (AI) will improve upon the glucose control 
currently achieved by open loop systems, and may improve the outcomes 
of critically ill patients, including those with COVID-19. This Earl Feasibility 
Study (EFS) 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 2 diabetes in a clinical 
research center (CRC) setting. Subjects with type 2 diabetes have been 
chosen as they are insulin resistant, which makes their insulin resistance 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
2 
profiles like 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. 
 
Objectives: 
 
 
Primary Objectives:   
 
1. The primary safety objective of this first in human study is to test 
the hypothesis that an AI based closed loop glucose control system 
will be able to safely control the blood glucose levels of 
participants with type 2 diabetes during a 24 hour stay in the CRC 
setting. 
2. The primary efficacy objective of this first in human study is to test 
the hypothesis that an AI based closed loop glucose control system 
will effectively control the blood glucose levels of participants with 
type 2 diabetes during a 24 hour stay in the CRC setting. 
 
Secondary Objectives: 
 
The secondary objectives of this study are to test the hypothesis that an AI 
based glucose controller will be effective in minimizing glucose curve 
variations commonly observed in critically ill patients.   
Endpoints: 
Primary Endpoint: 
 
1. The primary safety endpoint will be the percent of all glucose 
values that are within the glucose range of less than < 70 
mg/dL. Time frame will be from start of use of AI controller 
until end of use of AI controller. 
2. The primary efficacy endpoint will be the percent of all glucose 
values that are within the glucose range of 70-180 mg/dL. 
Time frame will be from start of use of AI controller until end 
of use of AI controller. 
Secondary Endpoints:  
 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
3 
• 
Measure the percent of glucose values that are within clinically 
significant hypoglycemic range (glucose <54 mg/dL). 
• 
Measure the percent of glucose values that are within the 
moderate hypoglycemic range of 54-69 mg/dL. 
• 
Number of hypoglycemic events as measured by glucose < 70 
mg/dL. 
• 
Measure the percent of glucose values that are within the desired 
glucose control range of 100-140 mg/dL. 
• 
Measure the percent of glucose values that are within the range of 
70-140 mg/dL. 
• 
Measure the percent of glucose values that are within the 
hyperglycemic range of >140 mg/dL. 
• 
Measure the percent of glucose values that are within the range of 
70-180 mg/dL. 
• 
Measure the percent of glucose values that are within the 
hyperglycemic range of >180 mg/dL. 
• 
Mean glucose level. 
• 
Measure of dispersion – coefficient of variation (CV). 
• 
The study data will be used to determine the percentage of paired 
glucose values (continuous glucose monitor(s) and reference) in 
each zone using a Clarke error grid analysis.1 These calculations 
will be performed for each individual CGM system and for the 
glucose value used by the FUSION system for purposes of glucose 
control (a calculated average of the two CGM systems). 
• 
The study data will be used to determine if FDA standards for 
integrated continuous glucose monitoring (iCGM) systems have 
been met for glucose zones < 70 mg/dL, 70-180 mg/dL, and > 180 
mg/dL.2 These calculations will be performed for each individual 
CGM system and for the glucose value used by the FUSION system 
for purposes of glucose control (a calculated average of the two 
CGM systems). 
Time frame will be from start of the use of AI controller until end of use of 
AI controller. 
Study Population: 
Two participants with type 2 diabetes, male and non-pregnant females, 
ages 18-70 inclusive, admitted to a CRC. Participants will eat three 
standardized meals during their 24-hour closed loop glucose control study. 
Phase: 
Early Feasibility Study, First in Human. 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
4 
Description of 
Sites/Facilities Enrolling 
Participants: 
Emory University Hospital, a tertiary care facility located in Atlanta, 
Georgia, United States. Single center study, all enrollments within USA.  
Description of Study 
Intervention: 
The medical device to be tested is named FUSION and is a fully functional 
closed loop glucose control system (artificial pancreas). The system 
consists of three main components: 1) Two Dexcom G6 continuous glucose 
monitors (CGM) provide glucose values to the glucose control software, 2) 
Glucose control software that is run by an all in one Medical Computer 
that is mounted on a powered Medical Cart, and which uses an artificial 
intelligence technique to determine, in an iterative fashion, the infusion 
rates of intravenous (IV) insulin and/or dextrose into the type 2 diabetic 
subjects for purposes of controlling their blood glucose into the range of 
100-140 mg/dL, 3) Two syringe pumps that are used to infuse insulin 
and/or dextrose into the study subjects. These syringe pumps are 
connected by serial data cables to the Medical Computer that runs the 
glucose control software, and their infusion rates are controlled by the 
glucose control software. Reference Glucose Values are measured every 
10-60 minutes on a Yellow Springs Instrument (YSI) glucose analyzer to 
ensure subject safety. 
Study Duration: 
Six months. 
Participant Duration: 
Thirty-one hours. 
 
 
 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
5 
 
 
1.2 
SCHEMA 
 
 
Visit 1: 
Screening 
 
 
 
 
 
 
Visit 2: 
Enrollment 
Time -2 
Weeks to 
-1 Week 
Prior to CRC 
Study 
 
 
 
 
 
 
 
 
 
 
 
Visit 3: 
Time 0 to 
31 hours 
 
 
 
 
 
Total N = 6:  Screen potential participants by inclusion and exclusion criteria. 
Schedule eligible participants for Visit 2 = Enrollment 
 
End of 
study 
Total N = 2: Administer initial study intervention of placement of two Dexcom G6 CGM’s 
in the abdominal position on arrival to the CRC. 
Place two peripheral IV lines for study intervention. 
Once the two Dexcom G6 CGM’s begin to return glucose values to the Dexcom Receivers, 
and the subjects begin to consume their first study meal, commence the 24-hour closed 
loop glucose control session. The first study meal will be lunch, which will be served at 12 
Visit 3 must occur no later than 2 
weeks from Visit 2 
Total N = 4:  Screen potential participants by inclusion and exclusion criteria; obtain 
informed consent.  Obtain history, document. Perform baseline assessments. 
Record height and weight (Kg). Obtain blood work to include: 1) creatinine, 2) alanine 
aminotransferase (ALT), 3) hemoglobin, 4) hemoglobin A1C. For female subjects within 
age range of 18-55 obtain urine pregnancy test. For subjects whose labs do not exclude 
them from the study, proceed to Visit 3 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
6 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Visit 1: Screening 
 
Visit 2: Enrollment 
Time -2 weeks to – 1 week 
Visit 3: 
Perform Baseline assessments 
Place Dexcom CGM monitors 
Time 0 to 5 hours 
Visit 3: 
Perform closed loop glucose control session 
Time 5 to 29 hours 
Visit 3: 
Observe subject for two hours after 
completion of the closed loop glucose 
control session 
Time 29 to 31 hours 
Informed consent 
 
X 
 
 
 
Demographics 
X 
X 
 
 
 
Medical history 
X 
X 
X 
 
 
Administer study intervention 
 
 
X 
X 
X 
Concomitant medication review 
 
X 
 
X 
 
 
Physical exam 
 
X 
X 
 
 
Vital signs 
 
 
X 
X 
X 
Height 
 
 
X 
 
 
Weight 
X 
X 
X 
 
 
Hemoglobin and Hemoglobin A1C 
 
X 
 
 
 
serum ALT & creatinine 
 
X 
 
 
 
Pregnancy test a 
 
X 
 
 
 
Adverse event (AE) review and evaluation 
 
 
X 
X 
X 
Complete Case Report Forms (CRFs) 
 
X 
X 
X 
X 
a 
Urine pregnancy test (women of childbearing potential). 
 
 
 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
7 
2 
 
INTRODUCTION 
 
 
2.1 
STUDY RATIONALE- GLYCEMIC CONTROL IN THE ICU  
 
In the U.S. there are currently 80,000 adult ICU beds, and 6 million admissions per year of ICU patients 
into these beds.3 The cost to care for these ICU patients is approximately 150 billion dollars per year.4  
At least 75% of ICU patients suffer from dysglycemia – hypoglycemia, hyperglycemia and increased 
glucose variability.5 The hyperglycemia is the result of a relative insulin resistance that is caused by the 
elevation of the stress hormones glucagon, cortisol, growth hormone, epinephrine and norepinephrine 
in these critically ill patients.6 The hypoglycemia and increased glucose variability occur because of the 
ineffectiveness of the current methods of controlling blood glucose levels in these patients. 
 
Poor control as reflected by high rates of hypoglycemia, hyperglycemia, and increased glucose variability 
have been associated with increased morbidity and mortality rates in ICU patients. This deleterious 
effect is caused by impaired function of the infection fighting white blood cells, and by augmentation of 
the bodies’ inflammatory cascades, both of which can impair organ function including the kidneys, bone 
marrow, lungs and heart.6 A large prospective randomized study published in 2001 showed that tight 
glucose control in Intensive Care Unit (ICU) patients decreased their morbidity and mortality rates by 30-
40%.7 Over the past 20 years multiple studies have confirmed the benefits of effective glucose control in 
the ICU setting, with these benefits extending to all patients in the ICU, not just those with diabetes.8-11 
It should be noted these benefits have been seen in medical,12 cardiac,13 and trauma14 ICU settings. 
 

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ƚŚĂŶϴϭŵŐͬĚ>͕ĂŶĚĂƐĂƌĞƐƵůƚŚĂĚĂŶ
ŽǀĞƌĂůůŵŽƌƚĂůŝƚǇƌĂƚĞƚŚĂƚǁĂƐϰϲй
ůŽǁĞƌƚŚĂŶƚŚĞŐƌŽƵƉŽĨƉĂƚŝĞŶƚƐǁŚŽ
ƐƵĨĨĞƌĞĚĂƚůĞĂƐƚŽŶĞŚǇƉŽŐůǇĐĞŵŝĐ
ĞǀĞŶƚ͘ϭϱ
^ŚŽǁŶďĞůŽǁ; &ŝŐƵƌĞ ϭͿĂƌĞ ƚŚĞ
ĚĞůĞƚĞƌŝŽƵƐ ĞĨĨĞĐƚƐŽĨďŽƚŚŚŝŐŚĞƌ
ĂǀĞƌĂŐĞŐůƵĐŽƐĞǀĂůƵĞƐĂŶĚŝŶĐƌĞĂƐŝŶŐ
ŐůƵĐŽƐĞǀĂƌŝĂďŝůŝƚǇ ;sсĐŽĞĨĨŝĐŝĞŶƚŽĨ
ǀĂƌŝĂƚŝŽŶͿ ŝŶĂƐƚƵĚǇŽĨϰ͕Ϭϴϰ/h
ƉĂƚŝĞŶƚƐ͘ϭϲ
&ŝŐƵƌĞϭ– WĂƚŝĞŶƚƐĚŝǀŝĚĞĚŝŶƚŽƋƵŝŶƚŝůĞƐďĂƐĞĚŽŶƚŚĞŝƌĂǀĞƌĂŐĞ/hŐůƵĐŽƐĞůĞǀĞůƐ͘ĂĐŚƋƵŝŶƚŝůĞĨƵƌƚŚĞƌĚŝǀŝĚĞĚ
ďĂƐĞĚŽŶƚŚĞƉĂƚŝĞŶƚƐs͘sсŽĞĨĨŝĐŝĞŶƚŽĨsĂƌŝĂƚŝŽŶ͘ <ƌŝŶƐůĞǇ͕:ŽƵƌŶĂůŽĨŝĂďĞƚĞƐ^ĐŝĞŶĐĞĂŶĚdĞĐŚŶŽůŽŐǇ͕
ϮϬϬϵ͘
ƐĐĂŶďĞĚĞĚƵĐĞĚĨƌŽŵ&ŝŐƵƌĞϮ͕ƚŚĞďĞƐƚƉĂƚŝĞŶƚŽƵƚĐŽŵĞƐǁŽƵůĚďĞĂĐŚŝĞǀĞĚďǇŵĂŝŶƚĂŝŶŝŶŐĂŵĞĂŶ
ďůŽŽĚŐůƵĐŽƐĞůĞǀĞůŝŶƚŚĞƌĂŶŐĞŽĨϳϬͲϭϯϵŵŐͬĚ>ǁŚŝůĞĂƚƚŚĞƐĂŵĞƚŝŵĞŬĞĞƉŝŶŐƚŚĞǀĂƌŝĂďŝůŝƚǇ͕ĂƐ
ŵĞĂƐƵƌĞĚďǇƚŚĞĐŽĞĨĨŝĐŝĞŶƚŽĨǀĂƌŝĂƚŝŽŶ͕ƚŽůĞƐƐƚŚĂŶϭϱй͘

DKE^dZd/KEK&EZd/&//>/Ed>>/'E^>K^>KKW'>hK^KEdZK>^z^dD^
d,ZWhd/DK>/dz/EdzWϮ/d/Wd/Ed^
sĞƌƐŝŽŶϭ͘Ϭ͘ϰ
WƌŽƚŽĐŽů/DdϮϬϮϮͲϭKE&/Ed/>
Ϯϱ DĂƌĐŚ ϮϬϮϮ
ϵ
/ƚŝƐalso essential to maintain the ICU patient’s glucose level in the clinician prescribed range. ^ĞĞŶ
ďĞůŽǁ;&ŝŐƵƌĞϮͿĂƌĞ ƌĞƐƵůƚƐ ĨƌŽŵ Ϯ͕ϱϱϬŶŽŶͲĚŝĂďĞƚŝĐ/hƉĂƚŝĞŶƚƐ͘ϭϳ dŚĞƉƌĞƐĐƌŝďĞĚƌĂŶŐĞďĞŝŶŐƵƐĞĚĨŽƌ
ƚŚŝƐƐƚƵĚǇǁĂƐϳϬ– ϭϰϬŵŐͬĚ>͘&ŽƌƉƵƌƉŽƐĞƐŽĨĂŶĂůǇƐŝƐ͕ƚŚĞƌĞǁĞƌĞĂŶĞƋƵĂůŶƵŵďĞƌŽĨƉĂƚŝĞŶƚƐŝŶƚŚĞ
ŚŝŐŚƚŝŵĞŝŶƌĂŶŐĞ;d/ZŚŝͿĂŶĚůŽǁƚŝŵĞŝŶƌĂŶŐĞ
;d/ZůŽͿŐƌŽƵƉƐ͘dŚĞƉĂƚŝĞŶƚƐǁŝƚŚĂŚŝŐŚƚŝŵĞŝŶ
ƌĂŶŐĞ;d/ZŚŝͿŚĂĚĂŵĞĚŝĂŶƉĞƌĐĞŶƚƚŝŵĞŝŶ
ƌĂŶŐĞŽĨϵϰй͕ǁŚŝůĞƚŚŽƐĞǁŝƚŚĂůŽǁƚŝŵĞŝŶ
ƌĂŶŐĞ;d/ZůŽͿŚĂĚĂŵĞĚŝĂŶǀĂůƵĞŽĨϲϭй͘dŚĞ
ŽǀĞƌĂůůŵŽƌƚĂůŝƚǇƌĂƚĞĨŽƌƚŚĞƉĂƚŝĞŶƚƐǁŝƚŚĂůŽǁ
ƚŝŵĞŝŶƌĂŶŐĞǁĂƐϴϲйŚŝŐŚĞƌƚŚĂŶƚŚĞŚŝŐŚ
ƚŝŵĞŝŶƌĂŶŐĞŐƌŽƵƉ͘ dŚŝƐƐƚƵĚǇƐŚŽǁĞĚƚŚĂƚ
ŵŽƌƚĂůŝƚǇƌĂƚĞƐĚĞĐƌĞĂƐĞƐŝŐŶŝĨŝĐĂŶƚůǇǁŚĞŶƚŚĞ
ŐůƵĐŽƐĞƚŝŵĞŝŶƌĂŶŐĞϳϬ– ϭϰϬŵŐͬĚ>ĞǆĐĞĞĚƐ
ϵϬй͘EŽŶͲĚŝĂďĞƚŝĐ/hƉĂƚŝĞŶƚƐĂƌĞŵŽƌĞ
ƐƵƐĐĞƉƚŝďůĞƚŽƚŚĞĂĚǀĞƌƐĞĞĨĨĞĐƚƐŽĨ
ĚǇƐŐůǇĐĞŵŝĂƚŚĂŶĂƌĞĚŝĂďĞƚŝĐƉĂƚŝĞŶƚƐ͕ĂŶĚ
ŽǀĞƌĂůůƌĞƉƌĞƐĞŶƚϳϱйŽĨĂůů/hƉĂƚŝĞŶƚƐ͘
ĞƐƉŝƚĞƚŚĞŽďǀŝŽƵƐďĞŶĞĨŝƚƐŽĨƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽůƚŚĂƚĂƌĞƐĞĞŶŝŶ&ŝŐƵƌĞƐϭͲϯ͕ĂůŵŽƐƚĂůůƐƚƵĚŝĞƐƚŽ
ĚĂƚĞŚĂǀĞĨĂŝůĞĚƚŽĂĐŚŝĞǀĞĞĨĨĞĐƚŝǀĞƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽů͕ĞƐƉĞĐŝĂůůǇǁŚĞŶŝƚŝƐĚĞĨŝŶĞĚĂƐƚŝŵĞŝŶƌĂŶŐĞ
ŽĨϳϬͲ ϭϰϬŵŐͬĚ>ĞǆĐĞĞĚŝŶŐϵϬй͕ŚǇƉŽŐůǇĐĞŵŝĂ;фϳϬŵŐͬĚ>ͿƌĂƚĞŽĨůĞƐƐƚŚĂŶϬ͘ϭй͕ĂŶĚŐůƵĐŽƐĞ
ǀĂƌŝĂďŝůŝƚǇĂƐŵĞĂƐƵƌĞĚďǇĂsŽĨůĞƐƐƚŚĂŶϭϱй͘dŚŝƐŝŶĂďŝůŝƚǇƚŽĞĨĨĞĐƚŝǀĞůǇĐŽŶƚƌŽůďůŽŽĚŐůƵĐŽƐĞůĞǀĞůƐ
ŝŶĐƌŝƚŝĐĂůůǇŝůůƉĂƚŝĞŶƚƐŚĂƐůĞĚƚŽŝŶĐŽƌƌĞĐƚĐŽŶĐůƵƐŝŽŶƐĨƌŽŵƐŽŵĞƐƚƵĚŝĞƐ͘
/ŶĂůĂƌŐĞƌĂŶĚŽŵŝǌĞĚƉƌŽƐƉĞĐƚŝǀĞƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽůƐƚƵĚǇŽĨϲϭϬϰƉĂƚŝĞŶƚƐŬŶŽǁŶĂƐƚŚĞE/Ͳ
^h'ZƐƚƵĚǇ͕ϭϴ ƚŚĞƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽůŐƌŽƵƉ;ƌĂŶŐĞϴϭͲϭϬϴŵŐͬĚ>ͿĂĐƚƵĂůůǇŚĂĚŚŝŐŚĞƌŵŽƌƚĂůŝƚǇƌĂƚĞƐ
ƚŚĂŶƚŚĞĐŽŶƚƌŽůŐƌŽƵƉ;ŐůƵĐŽƐĞфϭϴϬŵŐͬĚ>Ϳ– Ϯϳ͘ϱǀƐϮϰ͘ϵйŵŽƌƚĂůŝƚǇƌĂƚĞƐ͘,ŽǁĞǀĞƌ͕ƚŚĞƚŝŐŚƚŐůƵĐŽƐĞ
ĐŽŶƚƌŽůŐƌŽƵƉŚĂĚĂƐĞǀĞƌĞŚǇƉŽŐůǇĐĞŵŝĂ;фсϰϬŵŐͬĚ>ͿƌĂƚĞŽĨ ϲ͘ϴй͕ǀĞƌƐƵƐϬ͘ϱйŝŶƚŚĞĐŽŶƚƌŽůŐƌŽƵƉ͘
dŚŝƐůĂƌŐĞŚǇƉŽŐůǇĐĞŵŝĂƌĂƚĞŝŶƚŚĞƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽůŐƌŽƵƉǁŽƵůĚŚĂǀĞƐŝŐŶŝĨŝĐĂŶƚůǇŝŶĐƌĞĂƐĞĚƚŚĞ
ŵŽƌƚĂůŝƚǇƌĂƚĞŽĨƚŚŝƐŐƌŽƵƉ͕ĂƐĐĂŶďĞƐĞĞŶĂďŽǀĞ;&ŝŐƵƌĞϭͿ͘dŚŝƐ ĐŽŶĨŽƵŶĚŝŶŐ ǀĂƌŝĂďůĞŵŽƐƚůŝŬĞůǇůĞĚƚŽ
ƚŚĞŚŝŐŚĞƌŵŽƌƚĂůŝƚǇƌĂƚĞŝŶƚŚĞƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽůŐƌŽƵƉ͘/ŶĂƉŽƐƚŚŽĐĂŶĂůǇƐŝƐŽĨƚŚĞŝƌŐůƵĐŽƐĞĚĂƚĂ͕
ƚŚĞE/Ͳ^h'ZŝŶǀĞƐƚŝŐĂƚŽƌƐŶŽƚĞĚƚŚĂƚƚŚĞƌĞǁĂƐĂŶĂƐƐŽĐŝĂƚŝŽŶďĞƚǁĞĞŶďŽƚŚŵŽĚĞƌĂƚĞ;ϰϭͲϳϬ
ŵŐͬĚ>ͿĂŶĚƐĞǀĞƌĞ;фсϰϬŵŐͬĚ>ͿŚǇƉŽŐůǇĐĞŵŝĂĂŶĚŵŽƌƚĂůŝƚǇ ƌĂƚĞƐŝŶƚŚĞƉĂƚŝĞŶƚƐƚŚĞǇƐƚƵĚŝĞĚ͘ϭϵ dŚĞ
ƉĂƚŝĞŶƚŐƌŽƵƉƚŚĂƚĚŝĚŶŽƚƐƵĨĨĞƌĨƌŽŵĂŶǇŚǇƉŽŐůǇĐĞŵŝĂŚĂĚĂŵŽƌƚĂůŝƚǇƌĂƚĞŽĨϮϯ͘ϱй͕ǀĞƌƐƵƐϮϴ͘ϱйĂŶĚ
ϯϱ͘ϰйŝŶƚŚĞŵŽĚĞƌĂƚĞĂŶĚƐĞǀĞƌĞŚǇƉŽŐůǇĐĞŵŝĂŐƌŽƵƉƐ;ƉфϬ͘ϬϬϭĨŽƌďŽƚŚŐƌŽƵƉƐͿ͘dŚĞŽĚĚƐƌĂƚŝŽƐŽĨ
ĚĞĂƚŚǁĞƌĞϭ͘ϲĂŶĚϮ͘ϲŝŶƚŚĞŵŽĚĞƌĂƚĞĂŶĚƐĞǀĞƌĞŚǇƉŽŐůǇĐĞŵŝĂŐƌŽƵƉƐĂƐĐŽŵƉĂƌĞĚƚŽƚŚĞƉĂƚŝĞŶƚƐ
ǁŚŽĚŝĚŶŽƚƐƵĨĨĞƌĂŶǇŚǇƉŽŐůǇĐĞŵŝĂ͘dŚŝƐĐŽŶĨŝƌŵƐƚŚĞŝŵƉŽƌƚĂŶĐĞŽĨĂǀŽŝĚŝŶŐŚǇƉŽŐůǇĐĞŵŝĂǁŚŝůĞ
ĂƚƚĞŵƉƚŝŶŐƚŽŵĂŝŶƚĂŝŶƚŝŐŚƚŐůƵĐŽƐĞĐŽŶƚƌŽůŝŶƚŚĞ/hƐĞƚƚŝŶŐ͘
d/ZŚŝ
d/ZůŽ
&ŝŐƵƌĞϮ– ƋƵĂů ŶƵŵďĞƌŽĨƉĂƚŝĞŶƚƐŝŶƚŚĞd/ZŚŝĂŶĚd/ZůŽŐƌŽƵƉƐ͘>K^
с>ĞŶŐƚŚŽĨƐƚĂǇ͘d/ZсƚŝŵĞŝŶƌĂŶŐĞ͘ <ƌŝŶƐůĞǇ͕ƌŝƚŝĐĂůĂƌĞ͕ ϮϬϭϱ͘
ϭͲϮ͘ϵ
ϯн

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
10 
After it was originally determined that tight glucose control improves ICU patient outcomes, multiple 
methods aimed at achieving tight glucose control in this challenging patient population were developed. 
The original method was paper based intravenous insulin dosing protocols.20 To utilize these, the nurse 
would manually measure the patient’s blood glucose level, then refer to the institutions paper based 
protocol to determine if any adjustment in the current intravenous insulin dose was needed, then go to 
the intravenous pump to make an adjustment to the intravenous insulin infusion rate. This cycle would 
repeat itself every 1-4 hours, and is referred to as open loop control, as there continues to be human 
intervention in the control process. 
The next step in improving glucose control was to utilize two standard engineering control methods. 
Glytec LLC, has created glucose control software based on a Proportional Derivative  technique.21 This 
glucose control software is sold to hospitals as Glucommander, and serves to replace home grown paper 
based protocols, although it is still an open loop method. The nurse still manually measures the patient’s 
blood glucose level, enters the value into the Glucommander software, and then manually enters the 
new insulin dose recommended by the software into the bedside intravenous pump every 1-4 hours. 
Monarch Medical Technologies utilized a Model Predictive Control technique to create its EndoTool 
glucose control software.22 This open loop system works similar to the Glucommander software. 
While the software-based insulin 
dosing calculators represent an 
improvement over paper-based 
protocols, they still are not capable 
of achieving a time in range (e.g., 
100 – 140 mg/dL) that exceeds 90%, 
while at the same time avoiding any 
significant time in the hypoglycemic 
range and reducing glucose 
variability. In a poster presentation 
presented at the 2016 American 
Diabetes Association meeting, it was 
noted that when Glucommander was 
used in 340 adult ICU patients with 
sepsis, it produced a time in range (70 – 180 mg/dL) of 72%, and a hypoglycemia (< 70 mg/dL) rate of 
0.51%.23 In a study done on 2,398 medical/surgical ICU patients, Glucostabilizer achieved a time in range 
(80-150 mg/dL) of 80.4% and hypoglycemia (<70 mg/dL) rate of 3.5%. In a study done on burn patients, 
Endotool was noted to achieve a time in range (80 – 110 mg/dL) of 47% and a hypoglycemia (<80 mg/dL) 
rate of 4.5%.24 In a multi-center medical ICU study on 508 patients, the Space GlucoseControl system 
Figure 3– Although different ranges were reported, none were able to 
achieve > 90% time in range. 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
THERAPEUTIC MODALITY IN TYPE 2 DIABETIC PATIENTS 
 
Version1.0.4 
Protocol IMT 2022-1                                                           CONFIDENTIAL  
25 March 2022 
 
 
 
11 
time in range (80-150 mg/dL) was 83% and hypoglycemia (<80 mg/dL) rate was 2.3%. These results for 
time in desired control range and hypoglycemia are summarized here (Figure 3, Figure 4). 
It should be noted that the 
standard of care for achieving tight 
glucose control in ICU patients is 
insulin delivery via the intravenous 
route, and that ICU nurses will 
spend 90-120 minutes per patient 
per day attempting to achieve tight 
glucose control with the current 
methodologies.25 
One of the reasons tight glucose 
control is so difficult to achieve is 
that the blood glucose versus time 
curve is highly nonlinear in nature. 
To achieve tight glucose control, a 
control system capable of handling 
a nonlinear state will need to be employed. Most prior attempts to achieve glucose control utilizing 
control theory have employed Proportional, Integral, Derivative (PID) controllers.26 These controllers 
were originally developed for linear systems,27 thus they so far have enjoyed limited success in glucose 
control.23 Newer computerized glucose management systems, such as Endotool,28 utilize Model 
Predictive Control (MPC) theory29 and have enjoyed improved success compared to PID controllers in 
keeping blood glucose in the desired range, and limiting the incidence of hypoglycemia. However, these 
systems still focus solely on the glucose lowering effects of insulin and do not consider the glucose 
elevating effects of glycogenolysis/gluconeogenesis – from the liver. This causes them to have 
unacceptably high rates of hypoglycemia and low time in the desired range,30 thus they are not suitable 
in their current format for creating a closed loop glucose control system for use in the ICU setting. The 
failure of PID and MPC based glucose controllers to achieve safe and effective tight glucose control has 
led to the need to consider alternative control techniques. 
 
2.2 
STUDY RATIONALE – COVID-19 
 
 
Figure 4– Patient types treated were: Sepsis (Glucommander), 
medical/surgical ICU (GlucoStabilizer), burn ICU (Endotool), medical ICU 
(Space GlucoseControl). Endotool and Space GlucoseControl hypoglycemia 
rates are for < 80 mg/dL. 

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The current COVID-19 pandemic is 
caused by a Coronavirus that shares 
at least 80% of its RNA with the 
Coronavirus that caused the 2003 
SARS epidemic. During the 2003 
SARS epidemic it was shown that 
admission plasma glucose levels 
were an independent predictor of 
increased mortality rates (Figure 
5).31 
 
In a recently published article on 
over one-thousand U.S. COVID-19 
patients, it was shown that the 
presence of either diabetes or 
uncontrolled hyperglycemia in non-
diabetic patients increased 
mortality rates by more than 400% 
(Figure 6).32 The glucose metrics, 
mortality rates, and length of stay data for the two groups in this study are seen below (Table 1). 
Figure 5 – Patients were divided into terciles based on admission 
fasting plasma glucose (FPG) levels. Survival is correlated with the 
admission fasting plasma glucose (FPG). Low FPG 3.3-5.78 mmol/l, 
Medium FPG 5.78-7.9 mmol/L, High FPG 7.9-29.1 mmol/L. Yang, 
Diabetic Medicine, 2005. 

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No DM/No UH 
(N=671) 
DM/UH 
(N=451) 
p 
Mean admission glucose mg/dL 
114.5 (±20) 
202.4 (±118) 
<0.001 
Mean hospital glucose mg/dL 
116.6 (±25.9) 
178.5 (±71) 
<0.001 
% time in range > 180 mg/dL 
1.4 
39.1 
<0.001 
% time in range 70-180 mg/dL 
97.8 
59.9 
<0.001 
CV 
22.2 
39.8 
Not reported 
Mortality rate (%) 
6.2 
28.8 
<0.001 
Length of stay (days) 
4.3 
5.7 
<0.001 
Table 1 - Summary of data from study noted in Figure 7. DM – Diabetes Mellitus, No DM – No Diabetes Mellitus, 
No UH – No Uncontrolled Hyperglycemia, UH – Uncontrolled Hyperglycemia. Bode, Journal of Diabetes Science 
and Technology, 2020. 
Figure 6- Mortality rates 
among patients with 
diabetes or uncontrolled 
hyperglycemia (n=184), 
versus patients without 
diabetes or hyperglycemia 
(n=386). Diabetes defined as 
HbA1c >= 6.5%. 
Uncontrolled hyperglycemia 
defined as two glucose 
values >180 mg/dL in a 24-
hour period. The n=53 and 
n=24 represent the number 
of patients who died in each 
group. Bode, Journal of 
Diabetes Science and 

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Admission Glucose Level 
< 140 mg/dL 
(N=8,870) 
140-180 mg/dL 
(N=1,340) 
>180 mg/dL 
(N=1,102) 
Mortality Rate (%) 
15.7 
33 
41.1 
Number of Deaths 
1,394 
442 
453 
Table 2 - For the entire group, 61% of all deaths occurred in the group whose admission glucose levels were less 
than 140 mg/dL. Sanchez, Ann of Medicine, 2021. 
This study is the largest COVID-19 study published to date, and while it points out the importance of 
using the admission glucose level to predict mortality rates in hospitalized COVID-19 patients, it should 
be noted that the majority of deaths occurred in the group of patients whose admission glucose levels 
were less than 140 mg/dL. 
This points out the need to remain vigilant for the development of hyperglycemia after admission, in 
COVID-19 patients whose admission blood glucose levels are less than 140 mg/dL, as the previously 
noted study by Matmani demonstrated that the development of hyperglycemia within the first 24 and 
48 hours of hospitalization  has been associated with mortality (odds ratio 2.15 and 3.31, respectively).34 
The study by Matmani also demonstrated that non-diabetic patients admitted with COVID will often go 
on to develop hyperglycemia (e.g., > 140 mg/dL) after the first week of hospitalization (Figure 8), thus 
vigilance for the 
development of 
hyperglycemia may need to 
be extended throughout the 
entirety of their hospital 
stay. 
 
In a study performed in Italy 
it was shown that the 
presence of hyperglycemia 
(>7.7 mmol/L) on admission 
significantly increases 
mortality rates in COVID-19 
patients.36 
 
 
Figure 8 - This graph demonstrates that non-diabetic COVID-19 patients who develop 
hyperglycemia (e.g., > 140 mg/dL = 7.8 mmol/L), will often do so after their 7th day of 
admission (see yellow line above). The patients were divided into four groups based on 
their diabetes status (DM) and hyperglycemia (HG) status. Blue line represents no diabetes 
(DM-) and no hyperglycemia (HG-); yellow line no diabetes (DM-) but the presence of 
hyperglycemia (HG+); green line presence of diabetes (DM+) but no hyperglycemia (DM-); 
and red line presence of diabetes (DM+) and hyperglycemia (HG+). Matmani, MedRxiv, 
2020. 

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In this same study it was shown that in the 
group of 25 patients with hyperglycemia on 
admission, a non-randomized subgroup who 
electively chose to be treated with 
intravenous insulin versus usual care with 
subcutaneous insulin, that the improved 
glucose control produced by use of an 
intravenous insulin infusion significantly 
decreased mortality rates (Figure 9). The 
patients treated with intravenous insulin 
had a target glucose range of 7.77 – 9.99 
mmol/L. The patients treated with 
subcutaneous insulin received usual glucose 
control per their treating physician. The 
group treated with intravenous insulin were 
on the infusion for a mean of 32.7 ± 4.9 hours 
after entering the target glucose range of 7.77 
– 9.99 mmol/L. After cessation of the 
intravenous insulin, this group of treated 
patients received usual glucose control with 
subcutaneous insulin per their treating 
physician. 
 
One explanation for the improved outcomes in the patients treated with an intravenous insulin infusion 
may be a reduction in their inflammatory state and a reduction in their propensity to form blood clots, 
which are two common and most likely related conditions seen in COVID-19 patients.37-39 
 
Previous animal models of lung injury have confirmed that elevated blood glucose levels exacerbate 
lung inflammation, and that lowering of the blood glucose level with insulin effectively minimizes the 
degree of induced lung inflammation and edema based on wet lung weight, lung inflammatory markers, 
and on pathological specimens.40-42 These results have been confirmed in human studies that 
demonstrated the ability of acute hyperglycemia to induce increased cytokine levels.43 Furthermore, 
increased cytokine levels have been implicated in the development of ARDS in COVID-19 patients.44  
 
Finally, a laboratory study showed that when human peripheral monocytes are infected with CoV-2 
(COVID-19), the viral load of the monocytes after 24 hours of incubation in glucose containing medium 
was logarithmically related to the glucose level of the medium the monocytes were incubated in.45  This 
Figure 9 – Non-randomized initiation of insulin infusion in 
hyperglycemic (> 7.7 mmol/L on admission) COVID-19 patients. The 
No insulin infusion group were treated with subcutaneous insulin. 
Approximately 70% of patients in each group had diabetes. Sardu, 
Diabetes Care, 2020. 
Avg Glucose 138 mg/dL 
Avg Glucose 192 mg/dL 

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same laboratory study noted a similar effect on expression of the pro-inflammatory cytokine IL-1𝛽, 
which has been shown to be an important mediator of the cytokine storm seen in COVID-19 patients.46  
Although the optimal glucose control range for critically ill COVID-19 patients is unknown, a recent 
multi-center study demonstrated that average ICU glucose levels greater than 140 mg/dL increased 
COVID-19 mortality rates by almost 100% (Table 3).47 In this same study, a multivariable Cox regression 
analysis was conducted to assess predictors of ICU mortality. Age older than 60 (HR:3.21 [95% CI 1.78, 
5.78]) and hyperglycemia with mean ICU glucose >140 mg/dL (HR:1.79 [95% CI 1.14, 2.82]) were the 
only two predictors of increased ICU mortality. 
 
 
Average ICU glucose 
< 140 mg/dL 
(n=242) 
Average ICU glucose 
>= 140 mg/dL 
(n=253) 
p Value 
Mortality rate (%) 
16.6 
31.4 
< 0.001 
Mechanical 
Ventilation (%) 
37.2 
50.0 
<0.004 
ICU LOS 
3.5 
5.5 
< 0.001 
Table 3 – Diabetes present in 38.5% of entire cohort. For the entire cohort, the mean value of blood glucose at 
the time of admission was 186.6 mg/dL (SD+130.8). Saand, J Diabetes, 2020. 
To date, most attempts to control the glucose level of COVID-19 patients have met with only marginal 
success, as their glucose levels are highly variable and nonlinear, making them difficult to control using 
the current open loop techniques. In a retrospective analysis of 562 ICU admissions at a single medical 
center, the patients with COVID-19 had statistically significant worse glucose control, versus non-COVID-
19 ICU patients, despite attempts to control their glucose levels with the FDA approved GlucoStabilizer 
insulin dosing software program (Table 4).48 

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Table 4 – Table is from retrospective data analysis study comparing glucose control in ICU patients both with 
(n=93) and without (n=469) COVID-19. The ICU patients with COVID-19 had statistically significant lower percent 
time in range 70-150 mg/dL, compared to non-COVID-19 ICU patients. Kapoor, Journal of Clinical Medicine, 
2020. 
A multi-center retrospective analysis of 1,122 hospitalized COVID-19 patients demonstrated the 
importance of attempting to achieve good glucose control in this patient population. The group of 
patients with either diabetes or uncontrolled hyperglycemia had statistically significant worse glucose 
control (Table 5) and higher mortality rates. Inadequate glucose control occurred in the Diabetic and 
Uncontrolled Hyperglycemia group despite use of the FDA approved Glucommander insulin dosing 
software program.32 

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Table 5 – Glucose data from retrospective analysis of 1,122 patients with COVID-19. The group of patients with 
either Diabetes or Uncontrolled Hyperglycemia (two glucose values > 180 mg/dL in any 24-hour period) had 
statistically significant worse glucose control despite use of an FDA approved insulin dosing software program 
(Glucommander). Bode, Journal of Diabetes Science and Technology, 2020. 
In these open loop systems, the nurse manually checks the patient’s blood glucose level every 1-4 hours, 
enters the measured level into the insulin dosing software, and then manually enters the results of the 
insulin dosing software into the insulin infusion pump as depicted below (Figure 10). These systems do 
not utilize a dextrose (D-glucose) component for purposes of control, which makes them prone to 
periods of hypoglycemia. 

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Figure 10 – Depiction of the current process of glucose control in the ICU setting using an open loop method. 
With use of the current open loop glucose control technique ICU patients still experience high rates of 
hypoglycemia, hyperglycemia, low time in the desired glucose range, and large glucose variability.49  
In the U.S., as of March 17, 2021, there have been more than 29.6 million cases and 536,000 deaths due 
to COVID-19. The Center for Disease Control estimates that there will be 10-20,000 new COVID-19 
hospitalizations on a daily basis over the next month, and that currently 10-15% of all U.S. deaths are 
related to COVID-19.50 There are currently more than 50,000 COVID-19 patients hospitalized in the U.S.51 
Given the above information from COVID-19 clinical studies, the current status of the pandemic in the 
U.S., and the potential for tight glucose control to lower mortality rates in hyperglycemic COVID-19 
patients both with and without diabetes, development of a safe and effective closed loop glucose 
control system intended for use in COVID-19 patients is urgently needed. 
 
 
 
 

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2.3 
STUDY RATIONALE – FUSION AI BASED ARTIFICIAL PANCREAS SYSTEM 
 
The novel glucose control system to be tested in this study is an expert based rule system or Knowledge 
Based System.52,53 This system should be considered a form of artificial intelligence, whose main goal is 
to completely model the natural glucose homeostatic system. The essential elements of the native 
glucoregulatory system, which were used to create the AI based system under study, have been 
reviewed54 by Dr. Leon DeJournett, who is the developer of the novel AI based glucose controller to be 
tested in this study. If successful, this controller could be utilized in a closed loop glucose control system 
(artificial pancreas) for treatment of dysglycemia in ICU patients. 
 
Through an intensive review of how the native glucose control system functions (e.g., pancreas & liver), 
a knowledge based multiple input multiple output (MIMO) glucose control system has been 
developed.55 The algorithms of this system use the four input variables of absolute glucose, glucose 
rate of change, weight based intravenous insulin dose and weight based intravenous dextrose dose. 
Based on the values of these four input variables and the desired glucose control range, the two output 
variables of continuous intravenous insulin and continuous intravenous dextrose are adjusted. The 
results from the primary knowledge-based controller are also run through additional knowledge based 
controllers. These additional controllers monitor for outlying situations such as rapid falls or rise of 
blood glucose levels. These controllers will modify the two output variables from the primary controller 
if the clinical situation warrants such a change. Through utilization of the proper control techniques and 
frequent adjustment of the insulin and/or dextrose infusion rates (every 5 or 10 minutes), tight control 
of glucose will be achieved. In addition, episodes of clinically significant hypoglycemia will be avoided, 
and glucose variability will be minimized. 
 
The reason for proceeding to clinical studies at this time is that thorough preclinical studies of this 
controller have already been completed. These include the largest simulation study of a glucose 
controller published to date,56 and a comparative simulation study that showed clear superiority of the 
AI  based controller over Glucommander and several other ICU based glucose controllers.57 In addition, 
non-Good Laboratory Practice (GLP) animal testing using a swine model of stress induced 
hyperglycemia58 showed that the controller was able to achieve tight glucose control with no significant 
hypoglycemia.59 Finally, in a second larger animal study the artificial pancreas (AP) system demonstrated 
its ability to avoid severe hypoglycemia and minimize moderate hypoglycemia despite having to deal 
with an unannounced intravenous insulin injection.60 
3 
FUSION SYSTEM TESTING BACKGROUND  
 
The testing to date of the AI based glucose controller under study includes two simulation studies and 
two animal studies. Both simulation studies used a mathematical model of the ICU patients glucose-

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insulin system that has been clinically validated.61 The two AI controller outputs of insulin and dextrose 
were incorporated into the model, such that the controller’s outputs could attempt to bring control to 
the modelled system as the system experienced time variant changes of its internal parameters, or was 
perturbed through time variant exogenous infusions of intravenous dextrose. 
 
In the first simulation study, ICU “patients” were created through use of time variant changes in their 
insulin sensitivity, volume of distribution and half-life. In addition, variable rates of dextrose infusions 
were used to simulate potential clinical scenarios. The glucose sensor data also had variable degrees of 
accuracy ranging from 5-15%, and bias ranging from ± 0-10 mg/dL. Finally, three different starting 
glucose values and seven different control ranges were used. This led to 126,000 unique simulations, 
each done over a period of five days. This study produced 15 million hours of simulation time and 107 
million glucose values for analysis.56 As can be seen below (Figure 11), when the control range was set to 
100-140 mg/dL and the sensor error was 10%, the time in range of 70-140 mg/dL was 95%, which is 
consistent with the “time in range hi” group noted above (Figure 2).  
 
Figure 11 - SE = sensor error. DeJournett, Journal of Diabetes Science and Technology, 2016.  
The controller also did an exceptional job of avoiding any significant hypoglycemic events with an overall 
rate of hypoglycemia (< 70 mg/dL) of 0.09% with a sensor error of 10% as noted below (Figure 12). By 
adjusting the desired control range, clinicians can easily adjust the hypoglycemia rate towards zero, as 
was seen in the 100-140 mg/dL control range group. For the entire study there were no glucose values 
less than 45 mg/dL. 

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Figure 12 –Hypoglycemia defined as < 70 mg/dL.  SE = sensor error. DeJournett, Journal of Diabetes Science and 
Technology, 2016.  
As seen below (Figure 13), the controller was just as adept at minimizing glucose variability as noted by 
an average CV of 11.1% when the sensor error was 10%. The ability to minimize glucose variability to 
this degree should have a significant impact on ICU mortality rates as evidenced by the clinical results 
shown in  Figure 1 above. 
 
Figure 13 – SE = sensor error. DeJournett, Journal of Diabetes Science and Technology, 2016. 

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In a second simulation study the same mathematical model and time variant changes were used to 
create 80 virtual “patients,” and a novel random walk sensor error method was used that guaranteed an 
overall sensor error of 10%. This study utilized five, time variant exogenous dextrose infusions to 
perturb the model and produced a total of 400 five-day simulations per controller. The AI controller to 
be tested in the current study,55 which is being commercialized by Ideal Medical Technologies (IMT), was 
compared to the Yale protocol (YALE),62 Glucommander (GLUC),63 Wintergerst et al PID controller 
(PID),64 GRIP,65 and the NICE-SUGAR (NICE) study protocol66 in a comparative simulation study.57 Seen 
below (Table 6) is a summary of the results from this study. 
 
Severe 
Hypoglycemia 
Incidence (%) 
Mild 
Hypoglycemia 
(40-69 
mg/dL) 
Control 
range 
(100-140 
mg/dL)* 
Normoglycemia      
(70-140 mg/dL) 
CV 
(%) 
IMT 
0.00 
0.00 
(0.00-0.00) 
92.6 
(89.8-96.2) 
96.7 
(94.6-97.9) 
9.9 
(8.4-11.5) 
Yale 
0.25 
0.81 
(0.00-1.61) 
64.1 
(54.3-72.7) 
71.5 
(63.8-77.7) 
18.3 
(15.1-21.2) 
Glucommander 
4.50 
1.63 
(0.82-3.23) 
67.6 
(57.6-76.4) 
78.0 
(70.7-84.1) 
18.2 
(14.7-21.5) 
PID 
4.50 
0.80 
(0.00-2.43) 
63.8 
(52.5-71.2) 
75.7 
(67.8-81.4) 
19.1 
(15.9-22.3) 
GRIP 
6.25 
1.66 
(0.00-3.01) 
65.1 
(51.3-75.9) 
76.1 
(65.6-83.8) 
19.0 
(14.7-22.0) 
NICE 
2.50 
3.97 
(0.00-6.40) 
42.8* 
(33.6-52.6) 
89.0 
(80.9-95.1) 
20.6 
(17.0-24.2) 
Table 6 - Values are median (25-75) percent of all glucose values in given range and CV., Severe hypoglycemia is 
percent of simulations. *NICE results are for time in range 81-108mg/dL. DeJournett, Journal of Diabetes Science 
and Technology, 2017. 
As can be seen from Table 6 the IMT AI based controller showed clear superiority in this simulation 
study. It is important to note that the IMT controller achieved a time in range 70-140 mg/dL greater 
than 95%, a CV less than 15% and a hypoglycemia rate of 0. Per the previous noted clinical studies, all 
these results will correlate with improved survival of ICU patients, if they carry over to the real world 
setting. 
Although the FDA does accept simulation testing as a sole valid method to accomplish pre-clinical 
testing of glucose controllers,67-69 it was decided to perform two animal tests to assess the performance 
of IMT’s complete closed loop glucose control system in an in vivo setting. In the first small pilot animal 
study a fully functional closed loop glucose control system, which is essentially the same system to be 
tested in the current proposed study, was utilized to complete a twelve hour closed loop glucose control 

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study in a swine model of stress induced hyperglycemia.59 For this study the stressors to the 
anesthetized swine included endotoxin infusion to mimic sepsis,70 lung aspiration of hydrochloric acid to 
mimic acute respiratory distress syndrome,71 and a high dose of Solumedrol to mimic the stress 
hormone response seen in critically ill patients.72 The animals also received dextrose boluses to elevate 
their glucose levels at the start of the experiment, and high rates of dextrose infusions (5-10 mg/kg/min) 
to make glucose control difficult to achieve. In one scenario, the animals were under type 1 diabetes 
conditions through infusion of Octreotide,73 with C-peptide levels confirming lack of native insulin 
production. 
As noted below (Figure 14), the fully functional artificial pancreas (AP) system was able to maintain the 
blood glucose level in a normal swine range of 40-80 mg/dL in the animals that were rendered type I 
diabetics via an Octreotide infusion59 and simultaneously were in a state of stress induced 
hyperglycemia (SIH). While it is not surprising that the control animal that did not receive any insulin 
died, the important point is that the treated animal was able to achieve effective tight glucose control 
which produced a lower stress state as noted by a normal lactic acid level. 
 
Figure 14 - Dextrose bolus of 0.25 grams/Kg given at time 0, and dextrose infusion of 5 mg/kg/min from time 0-
12 hours. AP = artificial pancreas. Octreotide infusion used to create a type I diabetic state in both animals. 
DeJournett, Diabetes, 2016. 
As can be seen below (Figure 15), IMT’s AI based glucose control system was just as effective in 
augmenting the animal’s intact endogenous insulin production. Although the control animal was unable 
to bring its glucose level into the normal range throughout the course of the twelve hour experiment, 

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IMT’s AI based controller was able to bring the glucose level into the desired range within 4 hours, and 
maintain it within or close to the desired range throughout the rest of the experiment. It should also be 
noted that the untreated animal had elevated lactic acid levels compared to the animal that achieved 
effective tight glucose control with IMT’s AP system. 
 
 
Figure 15 - Dextrose bolus of 0.25 grams/Kg given and time 0, and dextrose infusion of 10 mg/kg/min from time 
0-12 hours. AP = artificial pancreas. Both animals had their endogenous insulin production left intact. 
DeJournett, Diabetes, 2016. 
In the second animal study the safety and performance of the FUSION system was assessed using a 
swine model of unannounced hypo- and hyperglycemia challenges. For this test the FUSION system was 
composed of the EIRUS (Getinge AB) CGM, which is a CE marked CGM designed for use in the ICU 
setting, the FUSION systems artificial intelligence-based (AI-based) glucose control software, and two 
syringe pumps. The study protocol is seen below (Figure 16). 
 
 

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Figure 16 – Protocol format. The ICU physician attempted to control to the range of 4.4 – 9 mmol/L, while the 
FUSION artificial pancreas system attempted to control to the tighter range of 4.4 – 6.6 mmol/L. The protocol 
was designed to induce hypoglycemia with a bolus of 3 units of insulin at time 20 minutes, and unavoidable 
hyperglycemia with a glucose infusion of 17 mg/kg/min from time 110 – 140 minutes as a means to test the 
artificial pancreas systems ability to avoid severe hypoglycemia after an unannounced insulin overdose and 
delayed moderate hypoglycemia secondary to treatment of the induced hyperglycemic state. DeJournett, 
Journal of Clinical Monitoring and Computing, 2020. 
The results from the fully autonomous FUSION system were compared to an ICU physician who had 
access to every 30-minute arterial glucose values and who used Dextrose 20% and NovoRapid to treat 
hypoglycemia and hyperglycemia. Both the control and treated animals had EIRUS CGM’s in place, and 
the glucose values from these CGM’s were used for statistical comparison. Noted below (Figure 17) are 
the median (25-75) glucose values from both groups. As can be seen from this graph the FUSION system, 
acting in a fully autonomous mode, was able to avoid both severe hypoglycemia after the insulin bolus 
and rebound moderate hypoglycemia secondary to treatment of the induced hyperglycemic state. The 
ICU physician, despite having access to every 30-minute arterial blood glucose values, was unable to 
avoid severe and moderate hypoglycemia. 
 

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Figure 17 – Median (25-75) glucose values from both groups. The FUSION artificial pancreas system had an 
improved safety profile despite controlling to the tighter range of 4.4 – 6.6 mmol/L. Treated = FUSION system, 
Control = ICU physician. 
Noted below (Table 7) is the performance of the FUSION system in the hypoglycemic range (<3.5 
mmol/L). It should be noted that none of the “Treated” animals experienced severe hypoglycemia and 
that all other measures related to hypoglycemia were significantly improved by the fully autonomous 
artificial pancreas system, despite the fact it was controlling to a tighter range which should have led to 
a higher rate of hypoglycemia as noted above (Figure 12). This study provides proof that an autonomous 
glucose control system that adjusts the rates of insulin and/or glucose infusions every 5-10 minutes 
should be able to outperform a bedside ICU physician, even when the physician has access to every 30-
minute arterial blood glucose values. 
 

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Table 7 - Hypoglycemia defined to be glucose less than 3.5mmol/L. All continuous data are reported as median 
(25-75).  All glucose data, and not just the data from the induced hypoglycemia episode from time 20min to time 
110min, were considered in these statistics. Statistical significance (p<0.05) indicated by *. A “hypoglycemic 
event” is defined as a sequence of hypoglycemic blood glucose values that is contiguous in time, terminated on 
both ends by a non-hypoglycemic value. † If an animal experienced any values less than 2.22mmol/L, it was 
counted as having experienced severe hypoglycemia - comparison made using the Fisher’s exact test. ††Area 
under the curve (AUC); area accumulated while glucose was less than this threshold. 
 
 
The medical device to be tested in this proposed CRC study is a fully functional closed loop glucose 
control system and is pictured below (Figure 18). 
 
 
 
 
Hypoglycemia Statistics 
Treated 
(N = 8) 
Control 
(N = 6) 
p value 
Number of animals with severe hypoglycemia† 
0 
5 
<0.003*  
Minimum glucose (mmol/L) 
2.83 (2.75-2.96) 
1.69 (1.68-1.89) 
0.033* 
Total time in hypoglycemia for all events (minutes) 
12.5 (10.5-16.0) 
41.0 (33.5-61.3) 
<0.004* 
Mean of all hypoglycemic glucose values (mmol/L) 
3.20 (3.07-3.24) 
2.80 (2.43-2.87) 
<0.033* 
Longest singular hypoglycemic event (minutes) 
9.5 (8.8-11.3) 
24.5 (20.8-29.8) 
<0.012* 
AUC†† 3.5mmol/L (mmol/L * minutes) 
4.8 (3.1-5.2) 
28.9 (21.1-54.2) 
<0.004* 
AUC†† 2.2mmol/L (mmol/L * minutes) 
0.0 (0.0-0.0) 
3.6 (1.3-5.2) 
<0.004* 
Dexcom G6 Receivers 

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DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
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31 
 
 
 
 
 
                  A                 B                                 C         D 
     
 
 
 
 
 
 
 
 
 
         E 
                             F                G                                   H                                                   I 
                               J 
 
 
 
 
 
 
        K 
                                     L 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
        M 
       N 
 
 
 
 
 
 
 
        O    P      Q 
                                       R 
 S                 T                   U              V 
 
 
 
 
       W 
 
 
 
 
 
 
 
 
 
        X  
 
 
 
         
Figure 19 – Screenshot of active glucose control software. 
 
 
          
A 
Patients weight in kg. 
B 
Unique identification number of study patient. 
C 
Glucose control range used for study in mg/dL. 
D 
Flashing green circle indicating software is functioning normally. 
E 
Note entry button – allows for entry of notes related to use of FUSION system. 
F 
Glucose versus time curve (blue line). 
G 
Dextrose infusion rate curve (green line). See right Y-axis for rate. 
H 
Insulin infusion rate curve (red line). See right Y-axis for rate. 
I 
Coefficient of variation statistic. 
J 
Upper limit of glucose control range (dashed light blue line). 
K 
Percent time in hyperglycemic range (> 140 mg/dL). 
L 
Lower limit of glucose control range (dashed light blue line). 
M 
Percent time in glucose control range (100-140 mg/dL). 
N 
Y axis (Glucose level in mg/dL). 
O 
Dextrose infusion rate (mL/hr). 
P 
Insulin infusion rate (mL/hr). 
Q 
Percent time in hypoglycemic range (< 70 mg/dL). 
R 
X-axis (Time in minutes). 
S 
Insulin infusion rate (U/kg/hr). 
T 
Dextrose infusion rate (mg/kg/min). 
U 
Total time elapsed since start of study (hours:minutes:seconds). 
V 
Next glucose value to be used by controller for purposes of glucose control. 
W 
Pause button to temporarily stop FUSION system. 
X 
Stop button to permanently stop FUSION system. 
 
 

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To date, the FUSION system has not been tested in humans. However, similar set ups have been 
previously used in the ICU setting to achieve tight glucose control. In a study published in 2013,74 the set 
up pictured below (Figure 20) was utilized, with the overall form factor being very similar to the FUSION 
system seen above (Figure 18). 
  
Figure 20 - Picture notes set up for fully functional closed loop glucose control system. System consists of a CGM 
placed in the abdominal position, a receiver for the CGM signal (Navigator Companion), a laptop housing the 
glucose control software, and two syringe pumps controlled by the MPC based glucose control software in the 
laptop. Leelarathna, Critical Care, 2013. 
 
For this 48-hour study on 24 ICU patients the control range was 6-8 mmol/L. The closed loop patients 
had Reference Glucose Values measured on a blood gas machine every 30 minutes to 6 hours. The MPC 
based closed loop controller used in this study automatically adjusted the flows of insulin and/or 20% 
dextrose every 5 minutes based on the input from the CGM, the desired control range, and the MPC 
controller. The control group patients were managed with a local insulin protocol and controlled to the 
same range. The results from this study are noted below (Figure 21). 

DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS A 
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Local Protocol 
(N=12) 
Automated closed-loop 
(N=12) 
p 
Primary end point 
 
 
 
Time glucose in target (%) (6.0-8.0 
mM) 
18.5 (0.1-39.9) 
54.3 (44.4-72.8) 
0.001 
Secondary end points 
 
 
 
Starting glucose (mM) 
10.8 (9.9-12.0) 
10.0 (8.9-11.1) 
0.21 
Mean glucose (mM) 
9.1 (8.3-13.0) 
7.9 (7.4-8.2) 
0.001 
Standard deviation of glucose (mM) 
1.9 (0.8) 
1.3 (0.5) 
0.089 
Time spent at glucose levels (%) 
 
 
 
   4.0-10.0 mM 
73.2 (21.2-89.4) 
93.3 (86.5-100.0) 
0.002 
   5.6-10.0 mM 
73.2 (21.2-82.4) 
92.2 (83.4-99.2) 
0.001 
   >8.0 mM 
78.4 (57.6-99.9) 
39.0 (23.5-51.4) 
0.001 
   >10.0 mM 
26.8 (10.5-78.8) 
6.7 (0-13.5) 
0.002 
   <6.0 mM 
0 (0-3.0) 
4.6 (3.1-8.3) 
0.028 
   <5.6 mM 
0 (0-0) 
0.7 (0-2.7) 
0.128 
   <4.0 mM 
0 (0-0) 
0 (0-0) 
NA 
Hypoglycemia 
 
 
 
   Episodes <4.0 mM 
None 
None 
 
   Hypoglycemia treatments 
None 
None 
 
Hyperglycemia 
 
 
 
   Number of subjects ≥ 15 mM 
5 (42%) 
1 (8%) 
 
   Number of subjects ≥ 17 mM 
4 (33.3%) 
1 (8%) 
 
   Episodes ≥ 15 mM 
11 
1 
 
   Episodes ≥ 17 mM 
13 
1 
 
Insulin infusion-data 
 
 
 
   Total units for 24 hours 
40.9 (34.9-101.4) 
57.4 (40.0-112.3) 
0.478 
   Hourly infusion rate 
1.7 (1.5-4.2) 
2.4 (1.7-4.7) 
0.478 
Total dextrose infusion for 48 hours 
(g) 
0.21 (0.0-5.2) 
NA 
NA 
Data shown are mean (SD) or median (interquartile range). 
Figure 21 – Data from study utilizing closed loop system shown above (Figure 20). Leelarathna, Critical Care, 
2013. 
  
Although the closed loop system in this study improved upon the results from the local protocol, it was 
only able to achieve a time in range 6-8 mmol/L of 54%, a time in range 3.9-8 mmol/L of 60%, and a CV 
of 16.5%. However, it did avoid any significant hypoglycemia. 
 
Effective tight glucose control can decrease ICU mortality rates as has been previously reported. In 
addition, significant improvement in morbidity is expected, as demonstrated by the only large 

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prospective tight glucose control study ever performed that achieved a high time in range while at the 
same time having no hypoglycemia. In this Japanese study of 447 pancreatic surgical patients,75 the tight 
glucose control group (80-110 mg/dL) had an 86% time in range, while the intermediate control group 
(140-180 mg/dL) had a 97% time in range, with neither group experiencing any hypoglycemia. The tight 
glucose control group had a 58% reduction in the surgical site infection rate as can be seen below 
(Figure 22). 
 
 
Figure 22 – Okabayashi, Diabetes Care, 2014. 
 
A large study done at the John Hopkins Health System estimated that surgical site infections (SSI) cost 
their system around $21,000 per infection, or around $3.3 million annually.76 There are around 150,000 
SSI’s per year in the U.S., thus tight glucose control in these patients has the potential to save around 
$1.8 billion per year.77  
 
This same Japanese closed loop glucose control study also demonstrated a 21% reduction in the length 
of stay in the more tightly controlled group, as noted below (Figure 23). 
 

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studies has been associated with increasing mortality rates,15,19 although a causal relationship has not 
been established. The immediate risk of a hypoglycemic event, especially a clinically important one with 
glucose values less than 54 mg/dL, is impaired brain function resulting in a temporary coma, or a 
hypoglycemia induced seizure.82,83 However, there does not appear to be any long term cognitive 
impairment in adults who have experienced hypoglycemic events.84,85 An additional potential risk of 
tight glucose control is the development of hypokalemia, which can lead to a prolonged Qt interval and 
potentially fatal  dysrhythmias. However, this issue has been reviewed and it was found that there was 
no association found between tight glucose control and development of prolonged Qt syndrome.86,87 
 
Hypoglycemia is a risk for any tight glucose control study, however the AI based FUSION glucose control 
system under study was particularly effective at avoiding hypoglycemic events in both the simulation 
and animal studies. When the control range was set to 100-140 mg/dL in the simulation studies, no 
glucose values less than 70 mg/dL were recorded in either study. Given these results and the current 
studies proposed control range of 100-140 mg/dL, no alternative procedures are warranted at this time. 
 
 
3.1.2 KNOWN POTENTIAL BENEFITS  
 
The immediate benefits for participants with diabetes in a brief (31 hour) tight glucose control study in a 
CRC setting are limited. However, development of a closed loop glucose control system designed for use 
in the inpatient setting may have long term benefits for this patient population, as preliminary studies 
have demonstrated improved outcomes through use of automated closed loop glucose control in this 
group in the non-ICU inpatient setting.88,89  
 
With regards to benefits to ICU patients, as has been previously noted, effective tight glucose control 
can lead to decreased morbidity rates, whether it be decreased wound infection rates in post-operative 
patients,75 or decreased renal failure and blood transfusions rates.7 In addition, mortality rates will be 
lower if the subject is able to maintain a high time in the control range,17 while at the same time 
avoiding any hypoglycemia events.15 Finally, safe and effective tight glucose control has the potential to 
lower critical illness related mortality including COVID-19 related mortality .36 
 
Long term potential benefits for the ICU patient population mainly relate to a shorter overall recovery 
period based on decreased complication rates and the potential for a shorter ICU length of stay to 
decrease mortality rates after hospital discharge.90 
 
3.1.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
 

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3.1.3.1 FAILURE OF DEXCOM G6 CONTINUOUS GLUCOSE MONITOR(S) 
The risk of complete failure of the continuous glucose monitoring system will be mitigated through use 
of two Dexcom G6 CGM systems, which will provide redundancy to this critical component of the 
FUSION artificial pancreas system. In addition, replacement of the Dexcom CGM system – sensor, 
transmitter, or receiver – will be allowed if any of these three components of an individual CGM system 
experiences a failure. 
 
The benefit of using the Dexcom G6 CGM is that the FDA has already approved this system for use as an 
integrated continuous glucose monitor (iCGM) in automated insulin dosing (AID) systems for use in 
treatment of patients with diabetes in the outpatient setting. This study and follow-up studies to be 
performed in the ICU setting will attempt to demonstrate the feasibility of using the Dexcom G6 CGM 
system in an AID system (e.g., FUSION) designed for use in the inpatient setting.  
 
In addition, the study will also demonstrate the ability of the Dexcom G6 transmitter to simultaneously 
transmit its glucose data to one medical device (e.g., the Dexcom G6 Receiver) and the Dexcom G6 App 
on a mobile phone placed 15 feet from the subject’s bed. Demonstration of this functionality is 
important, as a mobile phone device will be needed in the ICU setting to provide remote monitoring 
(e.g., outside of the room) of the subject’s continuous glucose measurements. 
 
3.1.3.2 USE OF INNACURATE CGM GLUCOSE VALUE FOR GLUCOSE CONTROL 
The risk of using an inaccurate CGM value for glucose control will be mitigated by averaging the glucose 
value of the two CGM devices. In addition, recalibration of the sensors will be performed as often as 
every 4 hours if there is a discrepancy of more than 20% between the CGM glucose values and that of 
the Reference Glucose Values. Independent Reference Glucose Values (YSI glucose analyzer) will be 
obtained frequently to ensure subject safety.  
 
The benefit of using Dexcom’s G6 CGM, which has already been approved as an iCGM, is to determine 
its accuracy in different scenarios/settings (e.g., participants with diabetes in the proposed study; 
COVID-19 patients in ICU in future study). 
 
The benefit of obtaining Reference Glucose Values every 10-60 minutes is to independently monitor for 
hypoglycemia in cases where the CGM systems are providing the FUSION system with false high glucose 
levels that could lead to hypoglycemia. The Reference Glucose Values can be used to administer rescue 
doses of intravenous dextrose in cases of severe hypoglycemia (< 54 mg/dL) or moderate hypoglycemia ( 
54-69 mg/dL) with associated neuroglycopenia symptoms. 
 

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3.1.3.3 FAILURE OF REFERENCE GLUCOSE ANALYZER 
In cases where there is no Reference Glucose Value available for a period exceeding 40 minutes, the risk 
will be mitigated through termination of the study on that subject. An additional risk of relying on 
Reference glucose analyzers is that they may produce inaccurate independent glucose results. This risk 
will be minimized by using a YSI glucose analyzer, which is the gold standard analyzer used in glucose 
control research, and which has an accuracy rate of ± 2%. The risk will be further minimized through use 
of the Nova StatStrip Glucose Hospital Meter System as a backup reference analyzer. This is the only 
point of care glucose meter currently approved by the FDA for use in the ICU setting. 
 
3.1.3.4 FAILURE OF CONTROL ALGORITHM TO PERFORM AS EXPECTED 
 
The risk of the control software to not perform as expected has been mitigated through version control 
of the software. In addition, the rules and sequencing of the software have been independently verified 
by the both the designer of the software, and the software developer. Furthermore, the control 
software to be used in this study has been tested in two simulation studies and two animal studies with 
no instances of software failure, and excellent overall glucose control capabilities as demonstrated by 
the previously mentioned results. Finally, the glucose control software has undergone an independent 
verification and validation process by an outside company (JKI) that specializes in working with the 
LabVIEW engineering software suite used to create the FUSION systems glucose control software. The 
risks of software failure will be mitigated through independent monitoring of the subject’s glucose 
values to prevent the serious risk of hypoglycemia. Complete software failure during the study would 
lead to termination of the study. 
 
The benefit of using closed loop glucose control software is demonstration of the feasibility of using this 
software to create a complete glucose control system and outweighs the noted risks. 
 
3.1.3.5 FAILURE OF SYRINGE PUMPS TO ACCURATELY DELIVER DOSES OF INTRAVENOUS 
INSULIN AND DEXTROSE 
 
The risk of the syringe pumps to not accurately deliver doses of insulin and dextrose has been mitigated 
through assessment of their accuracy prior to the study using a balance scale technique.91 This testing 
has demonstrated the accuracy of the syringe pumps to be within ± 5% from the prescribed infusion 
rate/volume. In addition, the infusion pump output rates are monitored by the glucose control software 
every 10 seconds to ensure the pump output rates match the prescribed rates from the software. If 

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these rate differences are greater than 20%, the study is temporarily stopped until the syringe pump is 
replaced. 
 
The benefits of using the KDS Legato 100 syringe pumps is that they were designed to work with the 
LabVIEW software that was used to implement the glucose controller, have a demonstrated infusion 
rate accuracy of within ± 5%, and can detect intravenous line occlusion and alert the clinician to this 
condition (e.g., occlusion) if it is detected. 
 
3.1.3.6 RISK OF IMPROPER SYRINGE PUMP SET UP 
 
The risk of the study personnel to not properly set up and use the syringe pumps will be mitigated 
through pre-study tutorials on their use, in addition to making available a standard operating procedure 
(SOP) as to their original set up and ongoing use. In addition, an IMT representative will be present on 
site throughout the entirety of the 24 hours of closed loop glucose on each subject. 
 
The benefit of using the KDS Legato 100 syringe pumps is their highly accurate dosing and their 
compatibility with the LabVIEW software used to develop the FUSION closed loop glucose control 
system being tested in this study. It is expected that the KDS Legato 100 syringe pumps will not be part 
of the final FUSION system for which marketing approval will be sought. 
 
3.1.3.7 RISK OF HYPOGLYCEMIA 
 
The risk of hypoglycemia will be mitigated through independent analysis of the subject’s blood glucose 
levels every 10-60 minutes for hypoglycemia, using a Reference glucose analyzer (YSI). If the subject has 
a glucose value less than 54 mg/dL, they will be given 15 mL of 50% dextrose as an immediate rescue 
medication to prevent any significant side effects from hypoglycemia. If the subject has a glucose value 
in the range of 54-69 mg/dL and is exhibiting signs of hypoglycemia, they will be given 15 mL of 50% 
dextrose as an immediate rescue medication to prevent any significant side effects from hypoglycemia. 
If the subject has two episodes of severe hypoglycemia, as defined by a glucose less than 54 mg/dL, the 
study will be stopped on that subject. If two subjects each experience a glucose value less than 54 
mg/dL, the overall study will be stopped.  
 
The overall risks of the study are outweighed by the potential benefit of demonstrating the safety of the 
AI based glucose control software, which is the first step in testing this software with an eventual goal of 
using it to create a closed loop glucose control system for use in the hospital setting. 
 

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4 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
 
1.                   Safety 
 
To assess the hypothesis that an AI 
based glucose controller will 
provide safe glucose control in 
participants with type 2 diabetes 
consuming three meals over the 
course of the 24-hour closed loop 
glucose control session.  
 
 
 
 
 
 
 
 
 
2. 
Efficacy 
 
To assess the hypothesis that an AI 
based glucose controller will 
provide effective glucose control in 
participants with type 2 diabetes 
consuming three meals over the 
course of the 24-hour closed loop 
glucose control session.  
 
 
 
 
 
 
 
 
 
 
 
 
The percent of all glucose values that 
are in the hypoglycemic range, when 
the latter is defined as glucose 
values less than 70 mg/dL. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The percent of all glucose values that 
are within the range of 70-180 
mg/dL. 
 
 
 
 
 
 
Avoidance of 
hypoglycemia during 
tight glucose control 
leads to decreased 
mortality rates, and thus 
measurements of the 
rate of occurrence of 
hypoglycemia can be 
considered an 
assessment of the 
overall safety of the 
glucose control system 
under study. 
 
 
 
 
 
ICU mortality rates 
increase when patients 
experience both 
hypoglycemia (< 70 
mg/dL) and 
hyperglycemia (> 180 
mg/dL). Thus, testing 
the ability of the AI 
based glucose control 
system to maintain the 
study subjects in the 
range of 70-180 mg/dL 
will give an indication of 
its ability to avoid these 
two deleterious 
glycemic states. 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
 
 
 
Secondary 
 
 
 
The secondary objectives of the 
study are to assess the controller’s 
ability to minimize glucose curve 
measurements associated with 
increased ICU morbidity/mortality 
rates, and to maximize those 
measurements associated with 
decreased ICU morbidity/mortality 
rates. 
 
 
 
 
 
 
 
1. Measure the percent of glucose 
values that are within the severe 
hypoglycemic range of 0 – < 54 
mg/dL. 
2. Measure the percent of glucose 
values that are within the 
moderate hypoglycemic range of 
54-69 mg/dL.  
3. Number of hypoglycemic (< 70 
mg/dL) events. Each event 
separated by at least one glucose 
value >= 70 mg/dL. 
4. Measure the percent of all 
glucose values that are within the 
desired glucose control range of 
100 – 140 mg/dL.  
5. Measure the percent of glucose 
values that are within the range 
of 70-140 mg/dL.  
6. Measure the percent of glucose 
values that are within the 
hyperglycemic range of > 140 
mg/dL.  
7. Measure the percent of glucose 
values that are within the range 
of 70-180 mg/dL.  
8. Measure the percent of glucose 
values that are within the 
hyperglycemic range of > 180 
mg/dL.  
9.  Mean glucose level (mg/dL). 
10.  Measure of dispersion – 
coefficient of variation. 
11. The study data will be used to 
determine the percentage of the 
Dexcom’s G6 CGM’s glucose 
values in each zone using a Clarke 
 
The chosen secondary 
endpoints are routinely 
measured in glucose 
control studies and 
serve to provide a more 
complete picture of the 
AI based glucose control 
systems ability to both 
safely and effectively 
provide glucose control. 
 
 
 
 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
error grid analysis.1 This same 
calculation will be performed on 
the average of the two Dexcom 
G6 CGM systems used by the 
FUSION system for purposes of 
glucose control. 
12. The study data will be used to 
determine if the both the 
individual Dexcom G6 CGM 
systems and their average value 
meet FDA criteria for iCGM 
accuracy with the glucose zones < 
70 mg/dL, 70-180 mg/dL, and > 
180 mg/dL.2 
 
 
Tertiary/Exploratory  
 
 
None planned 
 
 
 
 
The glucose data for the above statistical analysis will be the glucose data used by the FUSION system 
for purposes of glucose control, unless otherwise specified. 
 
5 
STUDY DESIGN  
 
5.1 
OVERALL DESIGN 
 
Tight glucose control in the ICU setting is difficult to achieve. We hypothesize that a closed loop glucose 
control system based on artificial intelligence will improve upon the glucose control currently achieved 
by open loop systems. This non-randomized Early Feasibility First in Human Study at a single study site 
will test the ability of a prototype closed loop glucose control system to provide safe and effective 
glucose control in participants with type 2 diabetes , who have insulin resistance profiles that match 
those of ICU patients.61 The study will be performed in a CRC setting on two participants with type 2 
diabetes over a time period of thirty-one hours per subject. The subjects will all consume three 
standardized meals during the 24-hour period their blood glucose levels are being controlled by the 
FUSION system. Study volunteers will be recruited from the adult endocrinology clinics of Emory 
University and/or Grady Hospital in Atlanta. Identified subjects who have been screened and enrolled in 
the study will have the study completed within two weeks of enrollment. An interim data analysis is not 
planned.  

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5.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
A non-randomized Early Feasibility Study design was chosen as this represents a first in human test of 
this artificial intelligence based closed loop glucose control system. The main goal of the study will be to 
test the safety and efficacy of the FUSION closed loop glucose control system, as measured by the 
percent of glucose values less than 70 mg/dL (safety), and the percent of glucose values in the range of 
70-180 mg/dL (efficacy). Testing in the CRC setting was chosen as it is a highly monitored environment, 
and the subjects can be carefully chosen based on inclusion/exclusion criteria. 
 
5.3 
JUSTIFICATION FOR DOSE 
 
 
For safety reasons the maximal allowed insulin dose (e.g., NovoLog) will be 0.5 units/kg/hour and the 
maximal dextrose (D10NS) infusion rate will be 4 mL/kg/hour, except during periods of dextrose 
boluses, when the maximal infusion rate will be 6.25 mL/kg/hour over a 5-minute period. These limits 
are consistent with a similar prior study.74 
 
 
5.4 
END OF STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.3. 
 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial 
globally. 
 
 
6 
STUDY POPULATION 
 
6.1 
INCLUSION CRITERIA 
 
 
A. Participants with type 2 diabetes are eligible to be included in the study only if they meet all the 
following criteria: 
 
1. Are 18-70 years of age, inclusive. 

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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 2 diabetes for a period of at least 3 months. 
4. Use insulin injections at home for glucose control. 
5. Have a hemoglobin A1c (HbA1c) in the range of 7.0 – 10.0%. 
6. Have a hemoglobin in the normal range for sex: 
a. Females: 12-15.5 grams/dL. 
b. Males: 13.5–17.5 grams/dl. 
7. Have adequate venous access sites in upper extremities. 
8. Body weight between 40 – 150 kg. 
 
 
6.2 
EXCLUSION CRITERIA 
 
A. Type 2 diabetic subjects will be excluded from the study if they meet any of the following 
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: 
a. Hepatic failure or has alanine aminotransferase (ALT) greater than 3 times the upper 
limit of normal. 
b. Has an estimated GFR <30 ml/min/1.73 m2 or End Stage Kidney Disease on renal 
replacement therapy. 

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c. Have congestive heart failure greater than class 1 on the NYHA classification system. 
d. Have a history of seizures. 
e. Have a history of cerebrovascular accident. 
f. Have a history of ischemic heart disease. 
7. For female subjects of potential childbearing age (age 18 to 55) they will be excluded if: 
a. Pregnant. 
b. Refuse to agree to a pregnancy test at the time of enrollment. 
c. 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. 
 
6.3 
LIFESTYLE CONSIDERATIONS 
 
Not applicable. 
 
6.4 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants, to meet the Consolidated Standards of Reporting 
Trials publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any serious adverse 
event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a failure 
to meet all inclusion and exclusion criteria will not be rescreened for participation in the trial. 
 
 
6.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Participants with type 2 diabetes will be recruited from the Diabetes Center at Grady Hospital and 
endocrinology clinics at Emory Healthcare, located in Atlanta, Georgia.  All adult type 2 diabetic patients 
being cared for in these clinics will be screened for inclusion in the study. The original screening will 

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include age, weight, length of diagnosis of diabetes, use of insulin in the home setting, and their most 
recent HbA1c level. Potential subjects who pass these criteria will then be assessed for exclusion criteria. 
Potential subjects who pass the exclusion criteria will be approached for participation in the study. 
Willing participants will be scheduled for enrollment during visit 2. Subjects who sign an informed 
consent during visit 2 will have blood drawn to evaluate their hemoglobin, HbA1c, ALT and creatinine 
levels. Female subjects aged 18-55 inclusive who have signed an informed consent will also have a urine 
pregnancy test performed during visit 2.  It is anticipated that 6 adult type 2 diabetic subjects will need 
to be screened to yield 2 subjects for participation in the study. It is expected that the HbA1c 
requirement will eliminate 30% of potential enrollees.   It is expected that the exclusion criteria will 
eliminate another 30% of the remaining potential enrollees. Study participants will be compensated for 
participation in the study.  
 
7 
STUDY INTERVENTION 
 
7.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
7.1.1 STUDY INTERVENTION DESCRIPTION 
 
7.1.1.1 COMPONENTS OF CLOSED LOOP GLUCOSE CONTROL SYSTEM 
 
1. Two complete Dexcom G6 continuous glucose monitoring systems – Glucose sensor, 
Transmitter, and Receiver 
2. Two mobile phones with the Dexcom G6 App 
3. One Medical Computer and associated power cord 
4. One Powered Medical Cart and associated power cord 
5. Two KDS Legato 100 syringe pumps and associated power cords 
6. Two serial data cables to attach syringe pumps to Medical Computer 
7. Two serial data cables to attach Dexcom G6 Receivers to Medical Computer 
 
7.1.1.2 VISIT 1, SCREENING 
This screening visit includes evaluating the medical history, comprising preexisting conditions and 
concomitant medications of type 2 diabetic subjects being seen at the adult endocrinology clinics of 
Emory Healthcare, located in Atlanta, Georgia. Those subjects who meet study inclusion criteria, and 
who do not meet any study exclusion criteria, will be approached for participation in the study. Willing 

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participants will be scheduled for visit 2, for purposes of obtaining an informed consent and enrolling 
them in the study. 
 
7.1.1.3 VISIT 2, ENROLLMENT 
Subjects who volunteer for the study will have the study thoroughly explained to them during visit 2. 
Subjects who willingly volunteer for the study, after having all their questions answered, will sign an 
informed consent.  Subjects who have signed an informed consent will be assigned a unique 
identification number that will remain the same throughout the study. Those subjects who have signed 
an informed consent and whose lab results obtained during visit 2 do not exclude them from the study, 
will proceed to visit 3, which must occur within 2 weeks of the date of enrollment. The following 
instructions will be given to the subjects in preparation for visit 3: 
 
1. Subjects to fast after midnight on the evening prior to visit 3. 
2. If usually taking long-acting insulin in the PM, then on the evening prior to visit 3: 
a) Take half the usual evening dose of long-acting insulin if history of nocturnal hypoglycemia. 
b) Take the full usual dose of insulin if no history of nocturnal hypoglycemia. 
3. After admission to the CRC on the morning of visit 3,  subject to administer their short acting 
insulin based on the amount of carbohydrates ingested for breakfast after their CRC admission, 
and their blood glucose value measured just prior to breakfast, per their usual home routine. 
7.1.1.4 VISIT 3, TIME 0 TO 5 HOURS (PREPARATION FOR CLOSED LOOP GLUCOSE CONTROL 
STUDY) 
 
1. 
General 
All subjects will be admitted between the hours of 0630 to 0700 to a single patient CRC room large 
enough to hold the subject, study personnel and necessary equipment. The study equipment, at a 
minimum should include a cardiac monitor, pulse oximeter, intermittent blood pressure capabilities, and 
a resuscitation cart. 
2. 
Screening Prior to Initiation of the Closed Loop Glucose Control Session 
The subjects will be tested for the presence of diabetic ketoacidosis prior to proceeding to steps 3-6 
below. This testing will include: 
i. 
Blood glucose - If the blood glucose is > 300 mg/dL, the subject will be screened for 
blood ketones. 

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ii. 
Blood ketones - The study will be cancelled if the blood ketones are > 1 mmol/L. If blood 
ketones are > 1 mmol/L, a basic metabolic panel and venous pH will be obtained to rule 
out diabetic ketoacidosis. If diabetic ketoacidosis is confirmed, the participant will be 
stabilized per the usual routine care at Emory Healthcare. 
In addition, the closed loop glucose control session of the study will not be initiated if the participant has 
symptoms requiring action (e.g., abdominal pain, vomiting, unable to eat or drink, fever ≥ 101.5), 
regardless of blood sugar or ketone levels. 
3. 
Dexcom G6 CGM devices 
The subjects will have two Dexcom G6 CGM devices placed in the abdominal position, approximately 5 
cm to the left and right of the umbilicus. The CGM devices should be placed shortly after arrival to the 
CRC facility. For the Dexcom G6 CGM labeled “#1”, enter the glucose sensors four-digit code and the 
transmitters six-digit serial number into the Dexcom G6 Receiver labeled “#1” and into the Dexcom G6 
App on the mobile phone labeled “#1”. For the Dexcom G6 CGM labeled “#2”, enter the glucose sensors 
four-digit code and the transmitters six-digit serial number into the Dexcom G6 Receiver labeled “#2” and 
into the Dexcom G6 App on the mobile phone labeled “#2”. Position the mobile phones 15-20 feet from 
the bed the subject will be using during the study. 
 
4. 
Peripheral Intravenous Lines 
For purposes of medication infusion, all subjects will have a peripheral IV placed into the antecubital 
vein of one arm. For purposes of blood removal, all subjects will have an IV placed in the contralateral 
hand in a retrograde position. The hand with the retrograde IV will be warmed to 50-55 degrees Celsius 
with a commercial warming box or warming pad for purposes of arterializing the venous blood.93 
5. 
Reference Glucose Value 
After both Dexcom CGM’s have started to return glucose values to the Dexcom Receivers, and prior to 
starting the closed loop glucose control portion of study, a blood glucose value(s) (taken from 
arterialized hand IV line) will be measured using the YSI glucose analyzer. 
6. 
Calibration of Dexcom G6 CGM’s 
If the Dexcom G6 CGM values are more than 20 mg/dL different from the YSI glucose value for CGM 
values less than 100 mg/dL, or more than 20% different from the YSI glucose value for CGM values 
greater than or equal to 100 mg/dL, the Dexcom G6 CGM’s will be calibrated against the result from the 
YSI glucose analyzer (using the Dexcom G6 receiver(s)) prior to starting the closed loop glucose control 
study. If the YSI glucose analyzer is unavailable, the CGM will be calibrated using the Nova StatStrip 
Glucose Hospital Meter System. If the Dexcom G6 Receivers are recalibrated, the matching mobile 
phone’s Dexcom App must also be recalibrated at the same time (e.g., if Dexcom Receiver #1 is 
recalibrated, also recalibrate the Dexcom G6 App in mobile phone #1). If a Dexcom G6 sensor is 
recalibrated, a follow up CGM one hour after calibration must be within 20 mg/dL of the YSI Reference 
Glucose Value for CGM values less than 100 mg/dL, or within ± 20% of the YSI Reference Glucose Value 

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for CGM values greater than or equal to 100 mg/dL. If a CGM is felt to be inaccurate - cannot be 
calibrated to meet the aforementioned standards – it may be replaced. 
 
All blood for independent glucose analysis will be drawn from the retrograde venous line in the warmed 
hand. The drawn blood will be immediately analyzed for glucose in the preferential order of 1) YSI 
glucose analyzer, 2) Nova StatStrip Glucose Hospital Meter System. These blood glucose values will be 
known as the Reference Glucose Values. If the arterialized venous line stops working, it may be 
replaced. If an arterialized venous line is unavailable for blood draws for a period exceeding 40 minutes, 
the study on that subject will be terminated. 
 
All reference blood glucose values (both YSI and Nova StatStrip) will be manually recorded on the 
studies case report form, however, they will not be used by the FUSION system for purposes of glucose 
control (except to calibrate the Dexcom G6 CGM’s, as necessary). 
 
All subjects will be allowed to drink water throughout the course of the study. No glucose containing 
drinks will be allowed during the closed loop portion of the study. Subjects will remain confined to 
either the bed or a bedside chair throughout the course of the study. Subjects will use a bedside 
commode for bathroom breaks in order to prevent any interruption to their closed loop glucose control 
session.  
 
The following supplies will be needed to complete the study: 1) four 4-way stopcocks, 2)  two IV tubing 
(non-microbore) of 12 foot length for purpose of attaching the glucose controllers syringe pumps to the 
subject, 3) Ten 60 mL BD syringes filled with D10 normal saline (study site research pharmacy to fill 
these 60 mL syringes using their standard sterile technique), 4) Four 60 mL BD syringes filled with 
NovoLog insulin mixed in normal saline to a concentration of 1 unit/mL (study site research pharmacy to 
fill these 60 mL syringes using their standard sterile technique). The FUSION system (Figure 18) will be 
supplied by the study sponsor. 
 
7. Resuming insulin regimen after the intervention 
 
On the morning after completing the study device insulin infusion patient will resume their home insulin 
according to their usual regimen:  
a)To take half the usual evening dose of long-acting insulin and resume long-acting insulin in the 
evening.  
b)Take the full usual dose of basal insulin if administering insulin in the morning prior to enrollment. 
7.1.1.5 VISIT 3, TIME 5 TO 29 HOURS (CLOSED LOOP GLUCOSE CONTROL SESSION) 
 

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The closed loop glucose control session will not begin until the following criteria has been met: 
1. Both Dexcom G6 CGM’s are returning glucose values and have been calibrated – if necessary; or 
replaced – if necessary.  
 
Please refer to the below SOP document for the calibration procedure for the Dexcom G6 CGM’s, setting 
up the FUSION system, and initiating it’s software: 
 
FUSION System SOP 
 
To better simulate how the FUSION system will be used in the ICU setting, no run-in period will be 
performed prior to the subject consuming the first meal. During the 24-hour closed loop glucose control 
study (time 5 to 29 hours), blood glucose control will be performed autonomously by Ideal Medical 
Technologies FUSION glucose control system.  For safety reasons, the subjects blood glucose will be 
independently measured every 10-60 minutes on a YSI glucose analyzer. These independent Reference 
Glucose Values will not be used by the FUSION system for glucose control. After 2-3 hours of confirmed 
CGM accuracy (e.g., from 0900 to 1200), the closed loop glucose control session will begin. The first 
meal consumed during the closed loop glucose control session will be lunch.  
 
Lunch will consist of 60 grams of carbohydrate (45-60% of total meal Kcal’s) and be consumed beginning 
at 1200 hours (the beginning of the closed loop glucose control session). Dinner will consist of 75 grams 
of carbohydrates (45-60% of total meal Kcal’s) and be consumed beginning at 1800 hours (6 hours after 
beginning of closed loop glucose control session). Breakfast will consist of 50 grams of carbohydrate (45-
60% of total meal Kcal’s) and be consumed beginning at 0800 hours the day after the closed loop 
session began (20 hours after beginning of closed loop glucose control session). 
 
Subjects will be allowed to have snacks between the hours of 2100 on day 1 and 0600 hours on day 2 of 
their CRC study. Subjects will preselect their breakfast, lunch, and dinner meal choices from the CRC 
menu prior to the study. These meals will be unannounced to the FUSION system. Once the closed loop 
glucose control period has ended after 24 hours of glucose control, the control software will be stopped, 
and the subject will be disconnected from all intravenous infusions. 
 
If the subjects are removed from the study due to the occurrence of two severe hypoglycemic events (< 
54 mg/dL), the subjects will have their glucose values measured with a Reference glucose analyzer (e.g., 
YSI) every 10 minutes, until their glucose values are > 80 mg/dL. They will then have additional glucose 
levels drawn every 30 minutes, until they have consistent glucose levels in the range of 80-250 mg/dL 
for a period of at least two hours. See Recovery Period (Page 91) for details with regards to 
subcutaneous insulin doses to be received prior to discharge from the Clinical Research Center. 
 

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The insulin and dextrose 60 mL medication syringes may not be used for more than 24 hours. Although 
the study should be terminated after a period of 24 hours (e.g., may not go longer than 24 hours), if for 
any reason the study period is longer than 24 hours (e.g., on orders from the principal investigator), the 
insulin and dextrose medication syringes must be exchanged for new medication syringes. To be clear, 
the insulin and dextrose medication syringes may not be used for a period of time exceeding 24 hours. 
 
7.1.1.6 VISIT 3, TIME 29 TO 31 HOURS (OBSERVATION AFTER CLOSED LOOP GLUCOSE 
CONTROL SESSION) 
 
At the end of the subjects 24 hour closed loop glucose control session, they will be fed lunch consisting 
of 60 grams of carbohydrate (45-60% of total meal Kcal’s). The subjects will resume control of their 
blood glucose per the protocol instructions (see IMT2022-1-P2) once the closed loop glucose control 
period has ended. After finishing their lunch, the subjects will continue to have their blood glucose level 
analyzed by the YSI glucose analyzer every 30 minutes. When their blood glucose is in the range of 80-
250 mg/dL for a period of at least two hours after the end of their closed loop glucose control session, 
their intravenous catheters will be removed, and they will be discharged from the CRC. If their blood 
glucose level is less than 80 mg/dL, they will be given additional snacks until their blood glucose is 
greater than 80 mg/dL. If the subjects require additional snacks, they will continue to have their blood 
glucose measured every 30 minutes by the YSI glucose analyzer until their glucose has been stable in the 
range of 80-250 mg/dL on four consecutive values, after which time their intravenous catheters will be 
removed, and they will be discharged from the CRC unit. If their blood glucose is greater than 250 mg/dl 
they will self-administer their usual short acting insulin per the protocol instructions and their blood 
glucose will be monitored every 30 minutes until it is less than 250 mg/dL, at which time they may be 
discharged from the CRC unit. 
 
If usually taking long-acting insulin in the PM, then on the morning after completing the study device 
insulin infusion: 
a)Take half the usual evening dose of long-acting insulin if history of nocturnal hypoglycemia. 
b)Take the full usual dose of insulin if no history of nocturnal hypoglycemia. 
7.1.1.7 STUDY TERMINATION  
 
On each subject the study will be immediately terminated for any of the following reasons: 1) subject 
experiences two glucose values less than 54 mg/dL, 2) subject develops a glucose value less than 54 
mg/dL, and a previous study subject has already experienced one or more glucose values less than 54 
mg/dL, 3) subject develops any other complications or symptoms that in the opinion of the principal 
investigator warrants stopping the study, 4) subject or subject’s legal representative requests 

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withdrawal from the study, 5) Reference Glucose Values not available for a period exceeding 40 
minutes, 6) One Dexcom G6 CGM glucose values are unavailable for a period exceeding 3 hours,  7) Both 
Dexcom G6 CGM glucose values are unavailable for a period exceeding 20 minutes, and 8) Any 
unanticipated adverse device effect (UADE). 
 
7.1.1.8 OTHER 
Refer to Protocol 1 (IMT2022-1-P1) for other materials needed to complete the study. 
Refer to Protocol 2 (IMT2022-1-P2) for meal challenge in diabetic subjects. 
 
7.1.2 DOSING AND ADMINISTRATION 
 
The dosing of intravenous insulin and intravenous dextrose will be determined by the glucose value 
measured by the Dexcom G6 continuous glucose monitors, the difference between this measurement 
and the desired glucose range of 100-140 mg/dL, the glucose rate of change, the current weight based 
doses of intravenous insulin and/or dextrose, and the rules of Ideal Medical Technologies FUSION 
glucose control system. 
 
7.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
7.2.1 ACQUISITION AND ACCOUNTABILITY 
 
Ideal Medical Technologies FUSION closed loop glucose control system that is to be utilized in this study 
will be hand delivered by a representative of Ideal Medical Technologies to the Emory University Clinical 
Research Center at least two weeks prior to the initiation of the study. This will allow for adequate in-
servicing of the principal investigator and all pertinent study personnel as to the use of the complete 
closed loop glucose control system. The study site will store this system in a secure location so that only 
study personnel who will be participating in the study will have access to it. After the study has either 
been completed or cancelled, all equipment supplied to the study site by Ideal Medical Technologies will 
be immediately returned to Ideal Medical Technologies (at Ideal Medical Technologies expense). 
 
7.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
Medical Device Labeling 
 

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The medical device under study in this Early Feasibility Study protocol will be labeled as follows: 
 
“Ideal Medical Technologies 
18 North Kensington Rd 
Asheville, NC 28804 
1-828-337-9960 
leondej@idealmedtech.com 
Storage & Operating temperature of 41-95 F 
Contraindicated for use in subjects with: 1) Creatinine > 3 mg/dL, 2) hepatic failure, 3) Alanine 
aminotransferase > 3 times the upper limit of normal, 4) Pregnancy, 5) Known sensitivity to 
NovoLog, 6) Known sensitivity to any components of the Dexcom G6 continuous glucose monitor 
sensors, 7) NYHA congestive heart failure classification > 1, 8) History of cerebrovascular accident, 
9) History of ischemic heart disease, 10) History of seizures 
Adverse effects: May cause hypoglycemia 
Hazards: None known 
Interfering devices: None known 
Interfering substances: Hydroxyurea, high dose acetaminophen (> 1 gram every 6 hours) 
CAUTION  Investigational device. Limited by Federal (or United States) law to 
investigational use" 
 
 
7.2.3 PRODUCT STORAGE AND STABILITY 
 
Store and operate all components of medical device under study at room temperatures in range of 41-
95 degrees Fahrenheit. 
 
 
7.2.4 PREPARATION 
 
Not applicable. 
 

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7.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Not applicable. 
 
 
7.4 
STUDY INTERVENTION COMPLIANCE 
 
Adherence to the study protocol will be determined on-site monitoring by Ideal Medical Technologies 
personnel during each closed loop glucose control session. In addition, any deviations from the study 
protocol will be documented on the CRF. Ideal Medical Technologies will review the CRF forms after 
each study session to ensure adherence to the studies inclusion criteria, exclusion criteria, and for the 
presence of a signed informed consent document. Please refer to the following document for the 
studies monitoring plan: 
 
001_IMT_CRC_T2DM_Clinical Monitoring Plan 
 
 
7.5 
CONCOMITANT THERAPY 
 
Not applicable. 
 
7.5.1 RESCUE MEDICINE 
 
The study site will supply rescue medication that will be obtained locally. The following rescue 
medications may be used: 
 
1. 15 mL of 50% Dextrose for intravenous delivery (IV push), every 10 minutes as needed. 
2. Glucagon (1 mg/mL) for Intramuscular or intravenous delivery. May give repeat dose 15 minutes 
after first dose. 
 
 The 50% dextrose and Glucagon rescue medications should be used to treat the following two 
conditions: 
 
1) Severe hypoglycemia, which is defined as a blood glucose value less than 54 mg/dL. 
2) Moderate hypoglycemia, which is defined as a blood glucose value in the range of 54-69 mg/dL, which 
is accompanied by any of the following neurological signs of hypoglycemia: Anxiety, irritability, sweating, 
hunger, shakiness, fatigue, pale skin, lethargy, seizures. 

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These medications will be hand pushed into the subject’s intravenous line by the study nurse, or given 
by intramuscular injection in the case of Glucagon. The date and time of rescue medication 
administration as well as the name and dosage regimen of the rescue medication will be recorded on 
the case report forms. 
 
 
8 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
8.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
On each subject the study will be immediately terminated for any of the following reasons: 
 
1. Subject experiences two glucose values less than 54 mg/dL. 
2. Subject experiences one glucose value less than 54 mg/dL, and a previous study participant has 
already experienced one or more glucose value less than 54 mg/dL. 
3. Subject develops any other complications or symptoms that in the opinion of the principal 
investigator warrants stopping the study. 
4. Subject or subject’s legal representative requests withdrawal from the study. 
5. Subject develops any signs of diabetic ketoacidosis (e.g., blood glucose > 300 mg/dL for more 
than 1 hour with simultaneous blood ketones > 1 mmol/L). 
6. For any unanticipated adverse device effect. 
 
If subjects are removed from the study due to hypoglycemia or the development of diabetic 
ketoacidosis, they will have ongoing monitoring and care in the CRC as noted in Recovery_Period. If a 
subject signs an informed consent but does not receive closed loop glucose control, they may be 
replaced. If a subject begins the closed loop glucose control portion of the study, they may not be 
replaced. 
 
8.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request. 
 
The reason for subject withdrawal or involuntary removal from the study will be recorded on the CRF. If 
subjects withdraw themselves from the study, no lab work will be obtained at the time of their 
withdrawal, other than one final blood glucose value.  If a subject signs an informed consent but does 

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not receive closed-loop glucose control, they may be replaced. If a subject begins the closed loop 
glucose control portion of the study, they may not be replaced. 
 
As the study is limited to 31 hours of glucose control/monitoring, no long term follow up will done for 
the subjects who either complete the study, or for those who are withdrawn for any reason, except as 
required to record and monitor any adverse events or unanticipated problems. 
 
8.3 
LOST TO FOLLOW-UP 
 
Not applicable. 
 
9 
STUDY ASSESSMENTS AND PROCEDURES 
 
9.1 
EFFICACY ASSESSMENTS  
 
The following procedures/evaluations will be performed on the subjects: 
 
1. Review of medical history and inclusion/exclusion criteria to determine eligibility for the study. 
This may be performed by any qualified study personnel. 
2. Obtain informed consent. This may be performed by any qualified study personnel. 
3. Draw blood for creatinine, alanine aminotransferase, hemoglobin and HbA1c. These labs will be 
analyzed in the hospital’s central laboratory. For women of childbearing age of 18-55 years 
inclusive, obtain a urine pregnancy test. Blood draw will be performed by any qualified 
personnel. If these results have already been obtained as part of the subject’s routine laboratory 
studies, the already obtained results may be used to assess the subject for inclusion/exclusion 
criteria. 
4. For subjects who have signed an informed consent and whose lab results do not exclude them 
from the study, an appointment for visit 3 will be set. This appointment must occur within 2 
weeks of the date the informed consent was signed.  
5. During visit 3, the subject will undergo closed loop control of their blood glucose level from time 
5 to 29 hours utilizing Ideal Medical Technologies FUSION closed loop glucose control system. 
Refer to the SOP for set up, initiation and use of this system. To initialize the glucose control 
software the study RN will enter the patient’s weight (Kg), study identification number, and 
initial Reference Glucose Value. The glucose control range of 100-140 mg/dL will be 
automatically defaulted to by the glucose control software. On initiation of the closed loop 
glucose control session the study RN will obtain a blood sample for glucose analysis from the 
arterialized venous line every 30 minutes. This blood sample will be immediately analyzed for 

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blood glucose on the YSI glucose analyzer and the Nova StatStrip Glucose Hospital Meter 
System. Results from these two tests will be entered into the appropriate case report form as 
soon as they become available. If the reference glucose level is stable after 4 hours of closed 
loop glucose control, it will be checked every 1 hour. If there is a 20% difference between the 
Reference Glucose Value and the Dexcom G6 CGM’s, a Reference Glucose Value will be obtained 
every 30 minutes. If the Reference Glucose Value is less than 70 mg/dL, it will be checked every 
10 minutes.  This process will repeat itself for the entire period of closed loop glucose control 
(time 5 to 29 hours). The study RN will be responsible for making sure the insulin and dextrose 
syringes in the syringe pumps being used for glucose control remain at least 25% full (at least 15 
mL volume remaining in 60 mL BD syringe) throughout the course of the closed loop glucose 
control study. 
6. A total of approximately 80 blood draws for glucose analysis will be obtained during the study. 
The blood volume removed with each blood draw will be 0.5 mL, for a total blood loss of no 
more than 50 mL’s. This is in addition to the 10 mL removed previously for lab analysis to verify 
eligibility for the study. The total volume of blood removed from the subject for purposes of 
completing this study should be less than 80 mL’s over a period of 2 weeks. 
7. At the conclusion of the study the two Dexcom G6 CGM’s and the two intravenous lines will be 
removed from the subject by the study RN. The subjects will be discharged from the CRC when 
they have met the discharge criteria noted in the study protocol (IMT2022-1-P2). 
 
 
The subjects who have participated in the study will be given the following information after conclusion 
of the study: 
 
1. Their average glucose value over the period of closed loop glucose control. 
2. Their CV value over the period of closed loop glucose control. 
3. Their percent time in range < 70 mg/dL over the period of closed loop glucose control. 
4. Their percent time in range 70-180 mg/dL over the period of closed loop glucose control. 
5. Their percent time in range > 180 mg/dL over the period of closed loop glucose control. 
 
 
9.2 
SAFETY AND OTHER ASSESSMENTS 
 
9.2.1 SAFETY 
 
The exclusion criteria which are used to screen for potential subjects eliminates those with hepatic 
failure, signs of significant hepatic disease as defined by an alanine aminotransferase greater than three 

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times the upper limit of normal, severe renal failure, subjects with significant congestive heart failure, 
subjects with a history of ischemic heart disease/cerebrovascular accident/seizures and eliminates all 
females who are pregnant. The purpose of these exclusion criteria is to avoid first in human trials on 
subjects with severe organ compromise, and exposure of a fetus to an untested medical device. 
 
Independently monitoring blood glucose values every 10-60 minutes will ensure subject safety should 
they experience hypoglycemia that the closed loop glucose control system is either unaware of or is 
unable to effectively treat. This monitoring will allow for early intervention in case the subjects 
experience severe hypoglycemia (< 54 mg/dL) or moderated hypoglycemia (54-69 mg/dL) with clinical 
signs of hypoglycemia. 
 
9.2.2 HALTING CRITERIA 
 
Halting guidelines: 
 
1. A subject experiences two glucose values less than 54 mg/dL. 
2. A subject develops a glucose value less than 54 mg/dL, and a previous study subject has already 
experienced one or more glucose values less than 54 mg/dL. 
3. A glucose level less than 70 mg/dL that results in signs of hypoglycemia, including anxiety, 
irritability, sweating, hunger, shakiness, fatigue, pale skin, lethargy, or seizures. 
4. A glucose level less than 70 mg/dL that alters the subject’s mental status/physical functioning 
and that requires assistance from another person for recovery. 
5. Two subjects develop diabetic ketoacidosis during the closed loop glucose control sessions. 
6. Any unanticipated adverse device effect. 
 
The halting criteria of two severe hypoglycemic events on any one subject, or one severe hypoglycemic 
event on any two subjects ensures that the study will be stopped if the FUSION closed loop glucose 
control system is not capable of preventing severe hypoglycemia from occurring. Additionally, the 
halting criteria of two subjects developing diabetic ketoacidosis will ensure the study is stopped if the 
FUSION system is not able to prevent the development of diabetic ketoacidosis. 
   
9.2.3 PHYSICAL EXAM/LABS 
 

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The visit 1 physical exam will be limited to recording the subject’s weight. No vital signs will be recorded. 
During the closed loop glucose control portion of the study the subject’s vital signs will be monitored 
with a frequency of at least every 1 hour. 
 
No EKG’s will be needed for purposes of completing this study. No radiologic studies will be needed for 
purposes of completing this study. 
 
The screening labs which are part of the exclusion criteria will be performed in the central laboratory. 
The blood for these labs will be stored as per institution specific guidelines as the study itself does not 
require that the blood used for these studies be stored for any length of time. The overall blood volume 
needed for purposes of completing the study is estimated to be approximately 50 mL but may be as 
much as 80 mL. 
 
9.2.4 SPECIAL ASSAYS 
 
The Reference glucose samples to be done at the bedside will be performed on a YSI 2900 glucose 
analyzer. The study personnel will require specialized training on use of the YSI 2900 glucose analyzer 
prior to initiating the study, if they have not previously been trained on its use. In addition, the study 
personnel will also need training on the use of the Nova StatStrip Glucose Hospital Meter System prior 
to initiation of the study. 
 
9.2.5 USE OF EXISTING MEDICAL RECORD DATA 
 
For purposes of performing the screening criteria the existing medical records available at the time of 
the subject’s routine visit to the adult endocrinology clinic will be used whenever possible. In addition to 
medical history and physical exam information, this may also include use of necessary lab work to 
include creatinine, alanine aminotransferase, hemoglobin, HbA1c, and urine pregnancy test.  
 
9.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
9.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related. 
 

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9.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 
 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, a persistent or significant incapacity, or substantial disruption of the ability to conduct normal life 
functions. Important medical events that may not result in death or be life-threatening may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the 
participant and may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition.  
 
 
9.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
 
9.3.3.1 SEVERITY OF EVENT 
 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines 
will be used to describe severity:  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. For 
purposes of this study, the following will be considered severe adverse events: 
 
1. Death 
2. A life threatening experience 
3. Persistent or significant disability/incapacity 
4. Seizure secondary to hypoglycemia 
5. Myocardial infarction that is temporally related to a hypoglycemic (< 70 mg/dL) event 

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6. Cardiac dysrhythmia that that is temporally related to a hypoglycemic (< 70 mg/dL) event 
7. Blood glucose < 54 mg/dL 
8. Diabetic Ketoacidosis: meeting all criteria: symptoms such as polyuria, polydipsia, nausea, or 
vomiting, serum ketones > 1.5 mmol/L, either arterial blood pH < 7.30 or venous pH < 7.24, or 
serum bicarbonate < 15. DKA is suspected as either the primary or a contributing cause for these 
findings. 
9. Considered severe for any other reason. 
Study site personnel must alert Ideal Medical Technologies Inc. or its designee of any severe adverse 
event (SAE) within 48 hours of investigator awareness of the event via an agreed upon method. Alerts 
issued via telephone are to be immediately followed with official notification on study-specific SAE 
forms. See attachment IMT2022-1-A1 for serious adverse event form. 
 
 
9.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial of a 
medical device, the medical device under study must always be suspect.  
 
• 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility 
that the study intervention caused the AE, or there is a temporal relationship between the study 
intervention and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
 
 
9.3.3.3 EXPECTEDNESS  
 
The principal investigator will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
 

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9.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an adverse event (AE) or severe adverse event (SAE) may come to the attention of 
study personnel during study visits or upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report CRF. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to medical device under study (assessed only by those 
with the training and authority to make a diagnosis), and time of resolution/stabilization of the event. 
All AEs occurring while on study must be documented appropriately regardless of relationship. All AEs 
will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The Principal Investigator or his designee will record all reportable events with start dates occurring any 
time after informed consent is obtained until 1 (for non-serious AEs) or 3 days (for SAEs) after the last 
day of study participation.  At each study visit, the investigator will inquire about the occurrence of 
AE/SAEs since the last visit.  Events will be followed for outcome information until resolution or 
stabilization. 
 
Unsolicited adverse events are not applicable to this study. 
 
 
9.3.5 ADVERSE EVENT REPORTING  
 
Adverse events will be reported by the Principal Investigator to the Institutional Review Board and study 
sponsor if in the opinion of the Principal Investigator the adverse event was caused by or related to use 
of the medical device under study. 
 
9.3.6 SERIOUS ADVERSE EVENT REPORTING  
 

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If during the course of this study a serious adverse event occurs, the Principal Investigator shall 
complete an Unanticipated Adverse Device Effect Form and submit to the study sponsor and to the 
reviewing Institutional Review Board (IRB) as soon as possible, but in no event later than 10 working 
days after the investigator first learns of the effect.  The study sponsor is responsible for conducting an 
evaluation of an unanticipated adverse device effect and shall report the results of such evaluation to 
the Food and Drug Administration (FDA), the IRB and the Principal Investigator within 10 working days 
after the sponsor first receives notice of the effect. Thereafter, the sponsor shall submit such additional 
reports concerning the effect as FDA requests. 
 
 
9.3.7 REPORTING EVENTS TO PARTICIPANTS  
 
Adverse Events and Serious Adverse Events will be reported to the participants of this study if in the 
opinion of the Principal Investigator they are related to the medical device under study. 
 
9.3.8 EVENTS OF SPECIAL INTEREST  
 
Any medical device malfunction that either impedes or prevents the carrying out of this study will be 
reported to the sponsor, IRB, and regulatory agencies. 
 
9.3.9 REPORTING OF PREGNANCY  
 
If during the course of this study, a subject has signed an informed consent and is found to be pregnant 
prior to the treatment phase of the study, this subject will be informed of the positive pregnancy test 
and the fact that this excluded them from the treatment phase of the study. 
 
 
9.4 
UNANTICIPATED PROBLEMS 
 
9.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
Unanticipated problems will be considered those that involve risks to participants or others to include, 
in general, any incident, experience, or outcome that meets all the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-

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approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
 
This definition could include an unanticipated adverse device effect, any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects. 
 
9.4.2  UNANTICIPATED PROBLEM REPORTING  
 
The Principal Investigator will report unanticipated problems (UPs) to the sponsor and the reviewing 
Institutional Review Board (IRB). The UP report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
This report shall be submitted as soon as possible, but in no event later than 10 working days after the 
investigator first learns of the effect. A sponsor who conducts an evaluation of an unanticipated adverse 
device effect shall report the results of such evaluation to the FDA, the reviewing IRB, and to the  
Principal Investigator within 10 working days after the sponsor first receives notice of the effect. 
Thereafter the sponsor shall submit such additional reports concerning the effect as FDA requests.    
 
 
9.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 

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Not applicable. 
 
10 STATISTICAL CONSIDERATIONS  
 
A formal Statistical Analysis Plan (SAP) will not be developed for this study, thus formal null and 
alternative hypothesis will not be stated. 
 
 
10.1 STATISTICAL MEASUREMENTS 
 
Primary Safety and Efficacy Endpoints:  
 
1. 
Safety 
The safety of the FUSION system will be determined by its ability to avoid hypoglycemia in adult type 2 
diabetic patients consuming three meals over a period of 24 hours. Safety will be measured by 
calculating the percent of all glucose values that are within the hypoglycemic range of less than 70 
mg/dL. 
 
Statistics – No statistical comparison will be made for this measurement. 
 
2. 
Efficacy 
The efficacy of the FUSION system will be determined by its ability to maintain glucose in the normal 
range in adult type 2 diabetic patients consuming three meals over a period of 24 hours. Efficacy will be 
measured by calculating the percent of all glucose values that are within the normal glucose range of 70-
180 mg/dL. 
 
Statistics – No statistical comparison will be made for this measurement. 
 
 
Secondary Efficacy Endpoints: 
 
The secondary objectives of the study are to assess the controller’s ability to minimize glucose curve 
measurements associated with increased ICU morbidity/mortality rates, and to maximize those 
measurements associated with decreased ICU morbidity/mortality rates. 
1. 
Measure the percent of glucose values that are within the severe hypoglycemic range of 0- <54 
mg/dL.  

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Statistics – No statistical comparison will be made for this measurement. 
2. 
Measure the percent of glucose values that are within the moderate hypoglycemic range of 54-
69 mg/dL. 
Statistics – No statistical comparison will be made for this measurement. 
3. 
Measure the number of hypoglycemic (< 70 mg/dL) events. 
Statistics – No statistical comparison will be made for this measurement. 
4. 
Measure the percent of all glucose values that are within the desired glucose control range of 
100-140 mg/dL.  
Statistics – No statistical comparison will be made for this measurement. 
5. 
Measure the percent of glucose values that are within the range of 70-140 mg/dL. 
Statistics – No statistical comparison will be made for this measurement. 
6. 
Measure the percent of glucose values that are within the hyperglycemic range of > 140 mg/dL. 
Statistics – No statistical comparison will be made for this measurement. 
7. 
Measure the percent of glucose values that are within the range of 70-180 mg/dL. 
Statistics – No statistical comparison will be made for this measurement. 
8. 
Measure the percent of glucose values that are within the hyperglycemic range of > 180 mg/dL. 
Statistics – No statistical comparison will be made for this measurement. 
9. 
Measure the mean glucose value in mg/dL. 
Statistics – No statistical comparison will be made for this measurement. 
10. 
Measure of dispersion – coefficient of variation. 
Statistics – No statistical comparison will be made for this measurement. 
11. 
The study data will be used to determine the percentage of paired glucose values (continuous 
glucose monitors and the average of the two continuous glucose monitors versus the YSI reference) in 
each zone using a Clarke error grid analysis.1 No statistical comparison will be made for this 
measurement. 
12. 
The study data will be used to determine if FDA criteria for iCGM accuracy have been met for 
the three glucose ranges of < 70 mg/dL, 70-180 mg/dL, and > 180 mg/dL. 
a. Statistics for iCGM glucose range < 70 mg/dL. 
i. Percent values within ± 15mg/dL of Reference glucose (Acceptable = >85%) 
ii. Percent values within ± 40 mg/dL of Reference glucose (Acceptable = >98%) 
iii. Percent of Reference Glucose Values > 180 mg/dL (Acceptable = none) 
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i. Percent values within ± 15% of Reference glucose (Acceptable = > 70%) 
ii. Percent values within ± 40% of Reference glucose (Acceptable = > 99%) 
c. Statistics for iCGM glucose range > 180 mg/dL 
i. Percent values within ± 15% of Reference glucose (Acceptable = > 80%) 
ii. Percent values within ± 40% of Reference glucose (Acceptable = > 99%) 
iii. Percent of Reference Glucose Values < 70 mg/dL (Acceptable = none) 
 
The glucose data for the above statistical analysis will be the glucose data used by the FUSION system 
for purposes of glucose control, unless otherwise specified. 
 
10.2 SAMPLE SIZE DETERMINATION 
 
As this is a first in human study of a medical device a statistically determined sample size was not used. 
Rather, the subject number of two was chosen as it was recommended by the FDA considering this is a 
first in human study of a high risk medical device. 
 
The anticipated dropout rate after subjects have begun closed loop glucose control is less than 10%, 
which should not significantly affect the study results. No interim analysis is planned. Given the small 
sample size no subgroup analysis is planned.  
 
10.3 POPULATIONS FOR ANALYSES 
 
Not applicable. All subjects who begin closed loop glucose control will be used for analysis. 
 
10.4 STATISTICAL ANALYSES 
 
10.4.1 GENERAL APPROACH 
 
The data will be presented as median and interquartile range (25-75), except for the Clarke error grid 
analysis which will be presented as percent of values in zones A, B, C, D and E.  
 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
1. To determine percent time in range < 70 mg/dL for each subject, the calculation is as follows: 
 
(# of glucose values in range < 70 mg/dL/total number of all glucose values) * 100 

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This result will be presented as median and interquartile range (25-75). 
 
2. To determine percent time in range 70-180 mg/dL for each subject, the calculation is as follows: 
 
(# of glucose values in range 70-180 mg/dL/total number of all glucose values) * 100 
 
This result will be presented as median and interquartile range (25-75). 
 
 
 
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
For the secondary endpoints that measure percent time in range, the values will be calculated as noted 
above in 9.4.2. These results will be presented as median and interquartile range (25-75).  
 
The number of hypoglycemic events less than 70 mg/dL will be presented as median and interquartile 
range (25-75).  
 
The mean glucose level will be presented as mean ± SD. 
 
The coefficient of variation will be presented as median and interquartile range (25-75). 
 
The Clarke error grid analysis will be presented as a graph of the Clarke error grid. The YSI and Dexcom 
G6 data will be analyzed to determine the percent of all values that are in zones A, B, C, D and E. 
 
The FDA criteria for iCGM systems will be presented as percent of the CGM values meeting the FDA’s 
criteria for each of the three glucose ranges.2 
 
 
10.4.4 SAFETY ANALYSES 
 
For the safety primary endpoint of percent time in range < 70 mg/dL, the calculation is as follows: 
 
(# of glucose values in range < 70 mg/dL/total number of all glucose values) * 100 
 
This result will be presented as median and interquartile range (25-75).  
 

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Each AE or SAE will be independently reported as percent of patients experiencing the event. SAE’s that 
require stopping the study prematurely will be separately reported in a table. If the principal 
investigator feels the AE or SAE’s are secondary to the intervention this will be reported in the final 
study summary. Any rescue medicine that is used per 6.5.1 will be separately reported as percent of 
subjects requiring rescue medicine. 
 
10.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
The following baseline characteristics will be recorded at the start of the study, 1) age, 2) sex, 3) 
duration of diabetes (years), 4) diabetes therapy at time of CRC study [e.g., insulin, oral anti-
hyperglycemic + insulin], 5) HbA1c level, 6) Height (cm), 7) Body weight (Kg), 8) body mass index [BMI], 
9) starting blood glucose (mg/dL). 
 
10.4.6 PLANNED INTERIM ANALYSES  
 
Planned interim analysis- None. 
 
 
10.4.7 SUB-GROUP ANALYSES 
 
Not applicable. 
 
10.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Not applicable. 
 
10.4.9 EXPLORATORY ANALYSES 
 
None planned. 
 
11 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
11.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
 
11.1.1 INFORMED CONSENT PROCESS 

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11.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.  The following consent materials are submitted with this 
protocol: 
 
IMT_CRC_T2DM_Informed Consent 
 
11.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
For subjects who are not native English speakers, a study site provided medical translator will be made 
available for purposes of reviewing the informed consent document and answering any questions the 
subject has with regards to the study or the informed consent document. Family members will not be 
allowed to serve as translators. 
 
11.1.2 STUDY DISCONTINUATION AND CLOSURE 

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This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study participants, the Institutional Review Board, 
the Investigational Device Exemption (IDE)/study sponsor and regulatory authorities.  If the study is 
prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform study 
participants, the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for the 
termination or suspension.   
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or FDA. 
 
 
11.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. No 
information concerning the study or the data will be released to any unauthorized third party without 
prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or medical device company supplying the medical device may 
inspect all documents and records required to be maintained by the Principal Investigator, including but 
not limited to, medical records (office, clinic, or hospital) and pharmacy records that are pertinent to the 
study, for the participants in this study. The clinical study site will permit access to such records. 
 

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The study participant’s contact information will be securely stored for internal use during the study. At 
the end of the study, all records will continue to be kept in a secure location for as long a period as 
dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at Emory University Healthcare. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be 
identified by a unique study identification number. The study data entry and study management 
systems used by Emory University Healthcare research staff will be secured, and password protected. At 
the end of the study, all study databases will be de-identified and archived at Emory University 
Healthcare. 
 
 
11.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Not applicable. 
 
11.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Medical Monitor 
Francisco J Pasquel, MD, MPH 
Assistant Professor of Medicine 
Division of Endocrinology, Metabolism, and 
Lipids 
Dr. Leon DeJournett 
Chief Medical Officer 
Emory University School of Medicine 
Ideal Medical Technologies 
Emory University School of Medicine 
Division of Endocrinology, Metabolism, and 
Lipids 
69 Jesse Hill Jr Drive SE 
Atlanta, GA 30303 
 
Ideal Medical Technologies 
18 N Kensington Rd 
Asheville, NC 28804 
404-778-1695 
  
828-337-9960 
fpasque@emory.edu 
leondej@idealmedtech.com 
 

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11.1.6 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of an Independent Safety Monitor (ISM) who will be a nurse 
with relevant expertise, whose primary responsibility is to provide independent safety monitoring in a 
timely fashion. This is accomplished by review of adverse events, immediately after they occur or are 
reported, with follow-up through resolution. The ISM evaluates individual and cumulative participant 
data when making recommendations regarding the safe continuation of the study. The ISM will provide 
input to both the Principal Investigator and the IRB. The ISM will be an employee of Emory University. 
 
 
11.1.7 CLINICAL MONITORING 
 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with ICH GCP, and with 
applicable regulatory requirement(s).  
 
• 
Ideal Medical Technologies will provide personnel to ensure safe use of its FUSION closed loop 
glucose control system and to monitor for adherence to all aspects of the study protocol 
throughout each of study sessions. The IMT personnel will be present on site throughout each 
24 hour closed loop glucose control session, however, IMT personnel will not interact with 
participants or their identifiable data. All study records will undergo a comprehensive review 
(100% data verification) by an Ideal Medical Technologies representative after completion of 
each study session to verify ongoing adherence to the study protocol. This review may occur 
remotely and must be completed prior to continuing with the subsequent study sessions. This 
review will include a monitoring report that will be sent to the PI via email prior to continuing 
with the study. Any issues raised during this review process must be addressed by the PI prior 
to continuing with the study. 
• 
Independent audits will not be conducted.  
 
The formal monitoring plan can be seen in the following document: 
 
001_IMT_CRC_T2DM_Clinical Monitoring Plan 
 

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11.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation, and completion.  An individualized quality management plan will 
be developed to describe a site’s quality management. 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written SOPs, the monitors will verify that the clinical trial is conducted, and data are 
generated and biological specimens are collected, documented (recorded), and reported in compliance 
with the protocol, ICH GCP, and applicable regulatory requirements (e.g., GLP, Good Manufacturing 
Practices (GMP)).  
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
 
11.1.9 DATA HANDLING AND RECORD KEEPING  
 
11.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
Principal Investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into REDCap, a FDA compliant data capture system 

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provided by Emory University Healthcare. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
 
 
11.1.9.2 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Council on Harminosation (ICH) region and until there are no pending or 
contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the IDE/study sponsor. It is the responsibility of the IDE/study sponsor to 
inform the investigator when these documents no longer need to be retained. 
 
 
11.1.10 
PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or Manual of 
Procedures (MOP) requirements. The noncompliance may be either on the part of the participant, the 
investigator, or the study site staff. As a result of deviations, corrective actions are to be developed by 
the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation.  All deviations must be 
addressed in study source documents and reported to the study sponsor.  Protocol deviations must be 
sent to the reviewing Institutional Review Board (IRB) per their policies. The Principal Investigator is 
responsible for knowing and adhering to the reviewing IRB requirements. The protocol deviations will 
also be reported to the FDA as required. 
 
 
11.1.11 
PUBLICATION AND DATA SHARING POLICY 

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This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. 
This study will be registered with ClinicalTrials.gov. 
 
For any peer reviewed articles submitted for publication that arise out of the results of this study, the 
Principal Investigator or the Principal Investigators designated co-investigator will serve as lead author. 
In addition, the following two Ideal Medical Technologies (sponsor) employees will also be named 
authors of any and all publications that arise out of the results of this study: 
 
1. Jeremy DeJournett 
2. Leon DeJournett 
 
 
11.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the medical device 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership has established policies and procedures for all study group members to disclose all conflicts 
of interest and will establish a mechanism for the management of all reported dualities of interest. 
 
Conflicts of interest: 
 
Leon DeJournett – Owns stock in Ideal Medical Technologies. 
 
Jeremy DeJournett – Owns stock in Ideal Medical Technologies. 

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11.2 ADDITIONAL CONSIDERATIONS 
This section should include a description of any additional considerations not currently covered in this 
protocol template, such as particular institutional or IRB-related requirements.  
 
11.2.1 DATA IDENTIFICATION 
Subjects who have signed an informed consent will be assigned a unique identification number that will remain the 
same throughout the study. This identification number will be used to identify the subject, for purposes of 
initiating the FUSION system at the start of the study. This number will be visible on the FUSION systems graphical 
user interface throughout the 24 hour closed loop glucose control session and will be the only subject identifier 
displayed on the FUSION systems graphical user interface. The FUSION systems graphical user interface will not 
display any information that could be used to directly identify the subject (e.g., name, date of birth, social security 
number). This study will use only de-identified data. 
11.2.2 ROLE OF IDEAL MEDICAL TECHNOLOGIES PERSONNEL IN STUDY 
Ideal Medical Technologies personnel will be present throughout the 24 hour closed loop glucose control session 
to assist the study personnel with use of the FUSION system. This assistance will be limited to the following: 
1. Explanation of the components of the FUSION system including the connecting cables and power cords 
2. Explanation of the powering up process of the FUSION system 
3. Explanation of how to use the two syringe pumps that are part of the FUSION system 
4. Explanation of how to load the insulin and dextrose medication syringes into the two syringe pumps 
5. Explanation of how to change the medication syringes used in the syringe pumps 
6. Explanation of the proper set up of the medication (e.g., insulin and dextrose) and carrier solution (e.g., ½ 
NS) intravenous lines 
7. Explanation of how to enter the data needed to initiate the FUSION system (e.g., unique identification 
number and weight in kg) 
8. Explanation of how to start the closed loop glucose control session 
9. Explanation of how to pause the closed loop glucose control session 
10. Explanation of how to end the closed loop glucose control session 
11. Explanation of how to extract study data from the FUSION system at the end of the closed loop glucose 
control session 
12. Explanation of how to power down the FUSION system 
13. Explanation of how to properly store the FUSION system 
 
Ideal Medical Technologies personnel will not attempt to interact with the study subjects in any way. Ideal Medical 
Technologies personnel will provide no medical care for the study subjects. Ideal Medical Technologies personnel 

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will not personally extract the study data from the FUSION system. Ideal Medical Technologies personnel will not 
analyze the study data (this analysis will be performed by Emory University study personnel). 
 
11.3 ABBREVIATIONS 
 
AE 
Adverse Event 
AI 
Artificial Intelligence 
ALT 
Alanine Aminotransferase 
AP 
Artificial Pancreas 
BD 
Becton Dickinson 
BMI 
Body Mass Index 
CGM 
Continuous Glucose Monitor 
CM 
Centimeter 
CRC 
Clinical Research Center 
CRF 
Case Report Form 
CT 
Computerized Tomography 
CV 
Coefficient of Variation 
dL 
Deciliter 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Forms 
EFS 
Early Feasibility Study 
FDA 
Food and Drug Administration 
G 
Gram 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HbA1c 
Hemoglobin A1c (glycosylated hemoglobin) 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
iCGM 
Integrated continuous glucose monitor 
ICH 
International Council on Harmonisation  
ICU 
Intensive Care Unit 
IDE 
Investigational Device Exemption 
IMT 
Ideal Medical Technologies 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
IV 
Intravenous 
KBS 
Knowledge Based System 
KDS 
KD Scientific 
Kg 
Kilogram 
L 
Liter 
LOS 
Length of Stay 

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mg 
Milligrams 
mg/dL 
Milligrams/deciliter 
MIMO 
Multiple Input Multiple Output 
min 
Minute 
mL 
Milliliter 
mL/kg/hour 
Milliliters/kilogram/hour 
mM 
Millimole 
mmol 
Millimole 
mmol/L 
Millimole/Liter 
MOP 
Manual of Procedures 
MPC 
Model Predictive Control 
n 
Number 
NA 
Not Applicable 
NIH  
National Institutes of Health 
NYHA 
New York Heart Association 
P 
Probability 
PD 
Proportional Derivative 
PI 
Principal Investigator 
PID 
Proportional Integral Derivative 
QA 
Quality Assurance 
QC 
Quality Control 
RN 
Registered Nurse 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SE 
Sensor Error 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
STAT 
Immediately 
TIR hi 
Time In Range high 
TIR lo 
Time In Range low 
units/kg/hour 
Units/Kilogram/hour 
unit/mL 
Unit/Milliliter 
UP 
Unanticipated Problem 
USA 
United States 
YSI 
Yellow Springs Instrument 
% 
Percent 

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11.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Herpe TV, Espinoza M, Haverbeke N, Moor BD, den Berghe GV. Glycemia prediction in critically ill patients 
using an adaptive modeling approach. J Diabetes Sci Technol 2007;1:348-56. 
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http://inpatient.aace.com/sites/all/files/Yale_IIP_MICU120-160_2011.pdf.) 

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Davidson PC, Steed RD, Bode BW. Glucommander: a computer-directed intravenous insulin system shown 
to be safe, simple, and effective in 120,618 h of operation. Diabetes Care 2005;28:2418-23. 
64. 
Wintergerst KA, Deiss D, Buckingham B, et al. Glucose control in pediatric intensive care unit patients 
using an insulin-glucose algorithm. Diabetes Technol Ther 2007;9:211-22. 
65. 
Vogelzang M, Zijlstra F, Nijsten MW. Design and implementation of GRIP: a computerized glucose control 
system at a surgical intensive care unit. BMC Med Inform Decis Mak 2005;5:38. 
66. 
NICE SUGAR study treatment algorithm. 2009. (Accessed 10-4-16, 2016, at 
https://studies.thegeorgeinstitute.org/nice/docs/ALGORITHM.pdf.) 
67. 
Man CD, Micheletto F, Lv D, Breton M, Kovatchev B, Cobelli C. The UVA/PADOVA Type 1 Diabetes 
Simulator: New Features. J Diabetes Sci Technol 2014;8:26-34. 
68. 
Kovatchev BP, Breton M, Man CD, Cobelli C. In silico preclinical trials: a proof of concept in closed-loop 
control of type 1 diabetes. J Diabetes Sci Technol 2009;3:44-55. 
69. 
Patek SD, Bequette BW, Breton M, et al. In silico preclinical trials: methodology and engineering guide to 
closed-loop control in type 1 diabetes mellitus. J Diabetes Sci Technol 2009;3:269-82. 
70. 
Schrauwen E, Cox E, Houvenaghel A. Escherichia coli sepsis and endotoxemia in conscious young pigs. Vet 
Res Commun 1988;12:295-303. 
71. 
Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol 
Physiol 2008;295:L379-99. 
72. 
Boonen E, Vervenne H, Meersseman P, et al. Reduced cortisol metabolism during critical illness. N Engl J 
Med 2013;368:1477-88. 
73. 
Hwu CM, Kwok CF, Chiang SC, et al. A comparison of insulin suppression tests performed with 
somatostatin and octreotide with particular reference to tolerability. Diabetes Res Clin Pract 2001;51:187-93. 
74. 
Leelarathna L, English SW, Thabit H, et al. Feasibility of fully automated closed-loop glucose control using 
continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial. Crit Care 
2013;17:R159. 
75. 
Okabayashi T, Shima Y, Sumiyoshi T, et al. Intensive versus intermediate glucose control in surgical 
intensive care unit patients. Diabetes Care 2014;37:1516-24. 
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Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital 
management perspective. JAMA Surg 2013;148:907-14. 
77. 
HAI Data and Statistics. 2016. (Accessed December 6, 2016, 2016, at 
https://www.cdc.gov/hai/surveillance/.) 
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Rhodes A, Ferdinande P, Flaatten H, Guidet B, Metnitz PG, Moreno RP. The variability of critical care bed 
numbers in Europe. Intensive Care Med 2012;38:1647-53. 

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National Health Expenditures 2015 Highlights. 2016. (Accessed December 6, 2016, at 
ttps://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-
reports/nationalhealthexpenddata/downloads/highlights.pdf.) 
80. 
Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multi-centre controlled trial on tight 
glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 
2009;35:1738-48. 
81. 
Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe 
sepsis. N Engl J Med 2008;358:125-39. 
82. 
Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest 2007;117:868-70. 
83. 
Krinsley JS, Keegan MT. Hypoglycemia in the critically ill: how low is too low? Mayo Clin Proc 2010;85:215-
6. 
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Diabetes C, Complications Trial/Epidemiology of Diabetes I, Complications Study Research G, et al. Long-
term effect of diabetes and its treatment on cognitive function. N Engl J Med 2007;356:1842-52. 
85. 
Hulkower RD, Pollack RM, Zonszein J. Understanding hypoglycemia in hospitalized patients. Diabetes 
Manag (Lond) 2014;4:165-76. 
86. 
Uijtendaal EV, Zwart-van Rijkom JE, de Lange DW, Lalmohamed A, van Solinge WW, Egberts TC. Influence 
of a strict glucose protocol on serum potassium and glucose concentrations and their association with mortality in 
intensive care patients. Crit Care 2015;19:270. 
87. 
Singleton MJ, Soliman EZ, Bertoni AG, Whalen SP, Bhave PD, Yeboah J. Effect of Intensive Glycemic and 
Blood Pressure Control on QT Prolongation in Diabetes: The ACCORD Trial. Diabetes 2020;69:2186-93. 
88. 
Thabit H, Hartnell S, Allen JM, et al. Closed-loop insulin delivery in inpatients with type 2 diabetes: a 
randomised, parallel-group trial. Lancet Diabetes Endocrinol 2017;5:117-24. 
89. 
Takahashi G, Sato N, Matsumoto N, et al. Preliminary study on glucose control with an artificial pancreas 
in postoperative sepsis patients. Eur Surg Res 2011;47:32-8. 
90. 
Williams TA, Ho KM, Dobb GJ, et al. Effect of length of stay in intensive care unit on hospital and long-term 
mortality of critically ill adult patients. Br J Anaesth 2010;104:459-64. 
91. 
Batista E. Calibration and use of syringe pumps.  16th International Congress of Metrology; 2013; Paris, 
France. 
92. 
Visentin R, Dalla Man C, Kudva YC, Basu A, Cobelli C. Circadian variability of insulin sensitivity: 
physiological input for in silico artificial pancreas. Diabetes Technol Ther 2015;17:1-7. 
93. 
Nauck MA, Blietz RW, Qualmann C. Comparison of hyperinsulinaemic clamp experiments using venous, 
'arterialized' venous or capillary euglycaemia. Clin Physiol 1996;16:589-602. 
94. 
Goldberg PA, Kedves A, Walter K, Groszmann A, Belous A, Inzucchi SE. "Waste not, want not": determining 
the optimal priming volume for intravenous insulin infusions. Diabetes Technol Ther 2006;8:598-601. 

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95. 
Liu D, Moberg E, Kollind M, Lins PE, Adamson U, Macdonald IA. Arterial, arterialized venous, venous and 
capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia. 
Diabetologia 1992;35:287-90. 
 

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Protocol 1 – Preparation of Subject for Visit 3 
(IMT2022-1-P1) 
 
1.1 
Study Materials (Visit 3) 
The following materials will be available in the subject’s CRC room for purposes of performing the closed 
loop glucose control study. 
A) 
Four 60 mL BD syringes filled with NovoLog insulin mixed in normal saline to a concentration of 
1 unit/mL (study site research pharmacy to fill these 60 mL syringes using their standard sterile 
technique). Must be available by 1200 hours on day of CRC study. 
B) 
Ten 60 mL BD syringes filled with D10 normal saline (study site research pharmacy to fill these 
60 mL syringes using their standard sterile technique). Must be available by 1200 hours on day 
of CRC study. 
C) 
One 500 mL bags of normal saline and one 500 mL bag of one-half normal saline and associated 
intravenous tubing needed to infuse via an intravenous pump. 
D) 
Two intravenous pumps (these are in addition to the IMT supplied syringe pumps used by the 
FUSION system). 
E) 
One hundred TB syringes for purposes of withdrawing blood from the arterialized hand vein. 
F) 
Nova StatStrip Glucose Hospital Meter System, including at least 100 glucose test strips. 
G) 
Yellow Springs Instrument (YSI) blood glucose analyzer that has been calibrated per the 
manufacturer’s specifications on the day of the study. This glucose analyzer should be allowed 
to equilibrate in the designated study room for a period of at least forty-eight hours prior to 
each subject’s study session. All YSI supplies of enough quantity to run one hundred blood 
samples must be available prior to starting the study. 
H) 
FUSION glucose control system (Figure 18) to be provided by the studies sponsor at least 2 
weeks prior to the studies onset. 
I)  
Four 12-foot lengths of non-microbore intravenous tubing for purposes of infusing solutions 
(e.g., insulin, D10NS, ½ NS) into the subject. 

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1.2 
Continuous Intravenous Infusion Set Up 
A) 
Run one-half normal saline at 10 mL/hour via the peripheral IV that will be used to infuse the 
insulin and/or D10NS. Refer to below diagram (Figure 24) for the setup of the 1/2NS, insulin, 
and dextrose lines. The intravenous tubing used for the insulin infusion should be flushed with 
50 mL of insulin solution prior to being connected to the peripheral IV.94 Run normal saline at 10 
mL/hour via the retrograde peripheral IV to maintain patency between blood draws. 
 
 
 
 
D10NS - FUSION 
½ Normal Saline 
Insulin - FUSION 
Figure 24 – Illustration of set up of insulin, dextrose, and normal saline infusions for the FUSION closed loop 
glucose control system. 

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Protocol 2 – Meal Challenge in Type 2 Diabetic Subjects 
(IMT2022-1-P2) 
MEAL CHALLENGE PROTOCOL 
Type 2 diabetic subjects will be admitted to the CRC between 0630 to 0700 hours after an overnight 
fast. 
Methods Overview: 
After admission to the CRC, catheters will be placed in one antecubital vein for purpose of insulin and or 
D10NS infusion, and in a contralateral arm vein in a retrograde fashion for purposes of blood draws. 
Precaution to Avoid Electrostatic Discharge from Affecting FUSION System 
Touching the FUSION system when your body has a build-up of static electricity may cause an 
electrostatic discharge (e.g., flow of electricity) into the FUSION system. It is unknown if this would 
adversely affect the performance of the FUSION system. In order to mitigate against the risk of study 
personnel introducing an electrostatic discharge into the FUSION system, the following precaution must 
always be taken prior to touching the FUSION system: 
1. Touch a metal table that is positioned near the FUSION system but is not in contact with 
the subject or the FUSION system. This procedure must be performed prior to each 
interaction (e.g., touching) with the FUSION system. 
Meal Challenge Protocol: 
• 
Obtain a YSI glucose value. If the Dexcom G6 CGM’s glucose value is > ± 20 mg/dL for CGM 
values < 100 mg/dL, or > 20% different for CGM values >= 100 mg/dL as compared to the YSI 
glucose value, the Dexcom G6 CGM’s Receiver will be calibrated using this YSI glucose value, 
prior to starting the study. If a CGM does not meet the aforementioned accuracy standards one 
hour after being calibrated, it may be replaced. 
• 
MAKE SURE BOTH DEXCOM G6 CGM’S ARE RETURNING GLUCOSE VALUES WITHIN THE 
AFOREMENTIONED ACCURACY STANDARDS, PRIOR TO STARTING THE STUDY. 
• 
Once both Dexcom G6 CGM’s have met the previously noted accuracy standards, and both 
Dexcom G6 CGM’s are returning glucose values, use the YSI glucose value taken at 1200 hours, 
to initiate the FUSION systems software for purposes of beginning the closed loop glucose 
control session (refer to SOP of FUSION system). 

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• 
Obtain Reference Glucose Values for analysis on the YSI glucose analyzer every 10-60 minutes 
between times 5 to 29 hours, based on the following criteria: 
1. Every 30 minutes for the first 4 hours of the closed loop session. 
2. Every 1 hour between hours 4-24 of the closed loop session, if the blood glucose is 
stable (e.g., in range of 80-180 mg/dL) during the first 4 hours of the study. 
3. Every 10 minutes if the Reference (e.g., YSI) glucose values are less than 70 mg/dL. 
Continue with every 10 minutes Reference Glucose Values until the Reference glucose 
levels are greater than 80 mg/dL. 
4. Every 10 minutes if the either of the Dexcom G6 CGM’s is less than 80 mg/dL. Continue 
with every 10 minutes Reference Glucose Values until the Dexcom G6 CGM glucose 
levels are greater than 80 mg/dL. 
5. Every 30 minutes if there is a greater than 20% difference between the Reference 
Glucose Value (e.g., YSI) and either of the Dexcom G6 CGM’s. 
6. Every 30 minutes if the Reference or Dexcom G6 CGM(s) have been greater than 200 
mg/dL for more than one hour consecutively. 
▪ 
If the Dexcom G6 CGM has alerted that the glucose level is more than 200 
mg/dL for more than one hour consecutively, test the subject’s blood for 
ketones to rule out development of diabetic ketoacidosis. If the blood ketones 
are greater than 1 mmol/L, call the study’s principal investigator for further 
instructions. 
• 
At time 5 hours ( ̴ 1200 hours on day 1) begin lunch with 60 grams of carbohydrate as soon the 
closed loop glucose control session begins (Figure 25). 
• 
At time 11 hours ( ̴ 1800 hours on day 1) begin dinner with 75 grams of carbohydrate. 
• 
At time 25 hours ( ̴ 0800 hours on day 2) begin breakfast with 50 grams of carbohydrate. 
• 
At time 29 hours ( ̴ 1200 hours on day 2) end the closed loop glucose control session and have 
the subject eat lunch with 60 grams of carbohydrates. 
• 
From time 29 to 31 hours ( ̴ 1200 to 1400 hours on day 2) measure the subject’s glucose values 
every 30 minutes using the YSI glucose analyzer. After conclusion of the closed loop glucose 
control session, when the subject has glucose values in the range of 80-250 mg/dL for a period 
of at least two hours, remove IV catheters from subject, and have subject self-administer insulin 
per the instructions noted in #15 below.  
• 
After conclusion of the closed loop glucose control session, if the subject has any glucose values 
less than 80 mg/dL, offer subject additional snacks, and recheck their blood glucose every 30 
minutes until it is greater than 80 mg/dL. After conclusion of the closed loop glucose control 
session, when the subject has glucose values in the range of 80-250 mg/dL for a period of at 
least two hours, remove their IV catheters and discharge the subject from the CRC unit. 

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• 
After conclusion of the closed loop glucose control session, if the subject has any glucose values 
greater than 250 mg/dL, have subject administer short acting insulin according to their usual 
home regime and recheck the subjects blood glucose value every 30 minutes until it is less than 
250 mg/dL for a period of at least two hours, then remove their IV catheters and discharge the 
subject from the CRC unit. 
 
Potential Problems. 
Severe hypoglycemia, less than 54 mg/dl may be associated with adrenergic response symptoms 
(tachycardia, sweating, palpitations) and neuroglycopenia symptoms (impaired cognition, coma, 
seizures).  Based upon previous studies, patients can sustain hypoglycemia for approximately 30 min to 
an hour. 
 
To avoid risk to our human subjects, vital signs will be monitored closely. Frequent independent glucose 
measurement will be performed (every 10-60 minutes) to minimize the risk of severe hypoglycemia (< 
54 mg/dL) or moderate hypoglycemia (54-69 mg/dL) with the above noted symptoms. The protocol calls 
for rescue doses of 15 mL of D50 for severe hypoglycemia or moderate hypoglycemia with symptoms. In 
addition, the study on any one subject will be terminated if they experience two severe hypoglycemia 
events (< 54 mg/dL). The overall study will be terminated if two subjects experience a severe 
hypoglycemia event (< 54 mg/dL).  
 
Patients with a history of cerebrovascular accident, seizure disorder, and ischemic heart disease will not 
be recruited for this study. 
 
 
 
 

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5.  Body Measurements: Weight:  __________ kg   Height:  __________ cm 
 
 
6.  Vital signs:  
Temp _______          RR _______          HR   ________     Time of collection: _____:_____ 
 
BP ______ / ______          Time of collection: _____:_____ 
 
7.  Perform Point of Care Testing (POCT) blood glucose (BG) with YSI glucose analyzer every 10-60 
minutes from time 5 to 29 hours (see Reference_Glucose_Values ) 
 
Result: _____ mg/dL, Time: _________ (24 hour clock) 
Note: Notify study team if the BG is < 70 mg/dl or > 300 mg/dl. 
 
8.  Dexcom G6 CGM(s) 
 
 Visit 3 (Time 0 to 5 hours): Place one Dexcom G6 CGM in the abdomen 5 cm to the right of the 
umbilicus. Place a second Dexcom G6 CGM in the abdomen 5 cm to the left of the umbilicus. Make 
sure the Dexcom G6 Transmitters are labeled “#1” and “#2”. These labels should be in a clearly 
visible position after the Transmitters have been attached to the Dexcom G6 glucose sensors. Once 
both Dexcom CGM’s begin to return glucose values, obtain a Reference Glucose Value using the YSI 
glucose analyzer. If either of the Dexcom CGM’s do not meet accuracy standards (see Calibration) 
they may be calibrated. If one hour after calibration the CGM(s) still do not meet accuracy 
standards, they may be replaced. The closed loop glucose control session may not begin until both 
Dexcom CGM’s meet accuracy standards. 
 
Visit 3 (Time 5 to 29 hours):  Inspect the CGM sites and ensure proper performance and 
communication to the two Dexcom G6 Receivers that are labeled “#1” and “#2”, and that are part 
of the FUSION system (Figure 18); ensure communication with the Dexcom G6 APP on the two 
mobile phones labeled “#1” and “#2”; replace CGM(s) if necessary. Inspect the CGM insertion sites 
for any potential adverse events (e.g., bleeding, skin irritation, infection).  Remove CGM(s) if 
necessary. 
 
9.  Research staff to calibrate and Quality Control the YSI 2900 glucose analyzer. 
 
10.  Two IV Catheters placements: 
- 
One antecubital intravenous line (for infusion of insulin and dextrose) with an 18-20 gauge 
catheter with two 3-way gang stopcock (insulin from FUSION system in first stopcock, 
dextrose from FUSION system in second stopcock). First stopcock closest to subject, second 
stopcock furthest from subject. 
- 
One IV (18-20 gauge catheter) in contralateral hand (from antecubital IV) placed in a 
retrograde fashion for purposes of blood draws. This hand to be warmed as noted below. 

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- 
Study nurse to inspect IV sites on an hourly basis, or whenever subject complains of pain at 
IV site. 
- 
  
a) Run ½ normal saline @ 10 mL/hr using a standard IV pump through the IV line used to 
infuse insulin and/or dextrose from the FUSION system. 
b) Run normal saline @ 10 mL/hr using a standard IV pump through the IV line used for 
blood draws. 
11.  Set the temperature to somewhere between 50-55 °C 
 
Arm with retrograde hand IV that is to be used for blood sampling will be kept warm by use of a 
heating pad or similar device to increase blood flow in order to achieve “arterialized” samples.95  
 
12.  Standard Blood Collection Protocol per CRC guidelines 
 
RN: Draw BG from retrograde line: Draw 0.5 mL blood to be transferred to micro-tubes for Study 
Site to process and measure using a YSI glucose analyzer and Nova StatStrip every 10-60 minutes 
(time 5 to 29 hours). 
 
13.  Meal Challenge Protocol 
Time 5 hours ( ̴1200 on day 1): Subject to consume lunch with 60 grams of carbohydrate. 
Time 11 hours ( ̴ 1800 on day 1): Subject to consume dinner with 75 grams of carbohydrate. 
Time 25 hours ( ̴0800 on day 2): Subject to consume breakfast with 50 grams of carbohydrate. 
 
Carbohydrates should make up 45-60% of the total Kcal’s of each meal. 
 
Time 5 to 29 hours: Closed loop control of blood glucose with FUSION system (Figure 18), to control 
range of 100-140 mg/dL. 
 
14.  RECOVERY PERIOD – Time 29 to 31 hours 
 
A. Time 29 hours - Subject to resume outpatient subcutaneous insulin injections: 
i. 
Subjects routinely injecting long acting insulin only in the morning will take a dose of long 
acting insulin at 2/3 of their normal dose. ___ units given at __ __  : __ __ (24 hour clock) 
 
ii. Subjects routinely injecting long acting insulin morning and evening will take a dose of long 
acting insulin at 1/2 their normal morning dose and be instructed to take their evening dose as 
usual. ___ units given at __ __:__ __ (24 hour clock) 
 
iii. Subjects routinely injecting long acting insulin only in the evening will take a dose of long acting 
insulin at 1/3 of their normal dose and be instructed to take their evening dose as usual. 
___ units given at __ __:__ __ (24 hour clock) 
 

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iv. Subjects will administer their short acting insulin at time 29 hours based on their 29 hour YSI 
glucose value and carbohydrate content of their lunch consumed at 29 hours, per their usual 
home routine – short acting insulin dose based on any needed correction dose and amount 
needed to cover carbohydrate content of lunch. 
 
B. Time 29 hours - Subject to consume lunch with 60 grams of carbohydrate. 
 
Check blood glucose every 30 minutes with YSI glucose analyzer – Times 29, 29.5, 30, 30.5, 31 
hours, etc., until blood glucose in range of 80-250 mg/dL for a period of at least two hours after 
the completion of the closed loop glucose control session. If the subject is removed from the 
study early due to the presence of hypoglycemia (e.g., < 54 mg/dL or < 70 mg/dL with 
neuroglycopenic symptoms), they will have ongoing monitoring in the CRC until they have had 
glucose values in the range of 80-250 mg/dL for a period of at least two hours. If their glucose 
values are less than 70 mg/dL, they will have Reference Glucose Values measured every 10 
minutes until such time as their glucose values are greater than 80 mg/dL. If the subject develops 
signs of diabetic ketoacidosis, they will have a basic metabolic panel and venous pH drawn. If the 
subject develops diabetic ketoacidosis, they will be stabilized and have ongoing care per the usual 
routine of Emory Healthcare. 
 
15.  Remove both IV catheters once the subjects blood glucose is in the range of 80-250 mg/dL for a 
period of at least two hours after the completion of the closed loop glucose control session. This 
criterion will not be met prior to time 31 hours ( ̴ 1400 hours of 2nd day in the CRC). May discharge 
from CRC unit once this criterion has been met. 
16.  End of Study Blood Glucose Level, BG: ____ mg/dL, Time: _________ (24 hour clock) 
 
Glucose must be between 80-250 mg/dL before discharge. 
 
17.  Subjects will be instructed to check their blood glucose levels at home using their blood glucose 
meter, after discharge from the Clinical Research Center, at the following times: 
1. On arrival at home. 
2. Before dinner. 
3. At 9 P.M. 
4. On awakening the next morning. 
 
Subject to call study coordinator with concerns they have about their glucose levels or any other 
issue. 
 
 
 

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Attachment 1 
Serious Adverse Event Report Form 
IMT2022-1-A1 
 
Serious Adverse Event 
An adverse event is any untoward medical event associated with use of a drug or drug delivery system in 
humans, whether or not it is considered related to a drug or drug delivery system. For purposes of this 
study, a Serious Adverse Event (SAE) is any adverse event from this study that results in one of the 
following outcomes: 
 
• 
Death 
• 
A life threatening experience 
• 
Persistent or significant disability/incapacity 
• 
Seizure secondary to hypoglycemia 
• 
Myocardial infarction that is temporally related to a hypoglycemic (<70 mg/dL) event 
• 
Cardiac dysrhythmia that that is temporally related to a hypoglycemic (<70 mg/dL) event 
• 
Any other complication related to hypoglycemia 
• 
Blood glucose < 54 mg/dL 
• 
Considered significant for any other reason 
 
 
 
 
 

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Serious Adverse Event (SAE) Report Form 
 
DEMONSTRATION OF AN ARTIFICIAL INTELLIGENCE 
BASED CLOSED LOOP GLUCOSE CONTROL SYSTEM AS 
A THERAPEUTIC MODALITY IN TYPE 2 DIABETIC 
PATIENTS 
 
Protocol Number: 
IMT2022-1 
Site:  _____________________________________ 
Pt ID: ________________________ 
 
 
1. 
SAE Onset Date:  _______________ (dd/mm/yyyy) 
2. 
SAE Stop Date: _________________(dd/mm/yyyy) 
 
3. 
Location of serious adverse event: _________________________________ 
 
4. 
Was this an unexpected adverse event?        Yes        No   
 
5. 
Brief description of participant(s) with no personal identifiers:  
Sex:   F    M      Age: ______    
 
Diagnosis for study participation: _____________________ 
 
6. 
Brief description of the nature of the serious adverse event (attach description if more space needed): 
___________________________________________________________________ 
__________________________________________________________________________ 
 
7. 
Category of the serious adverse event:   

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o Death – date __/___/___  (dd/mm/yyyy)  
 
    
o Complication from severe hypoglycemia 
o Life-threatening 
 
  
         
 
 
  
o Hospitalization- prolonged 
  
 
 
 
  
 
o Disability / incapacity 
 
o Required intervention to prevent permanent impairment 
Other:________________________________________ 
8. 
Intervention type:   
 
 Medication or Nutritional Supplement: specify___________ 
 Device: Specify: ________________________ 
 Surgery: Specify: ________________________ 
 Behavioral/Life Style: Specify: _____________________ 
 
 
9. 
Relationship of event to intervention: 
 
o  Related - The AE is known to occur with the study intervention, there is a reasonable possibility 
that the study intervention caused the AE, or there is a temporal relationship between the study 
intervention and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
 
o Not related - There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
 
10. 
Was study intervention discontinued due to event?   Yes    
No 
 
11. 
What medications or other steps were taken to treat serious adverse event?  

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12. 
List any relevant tests, laboratory data, history, including preexisting medical conditions 
 
 
 
 
13. 
 Type of report: 
 
  Initial   
  Follow-up 
  
  Final 
 
 
Signature of Principal Investigator: _______________________ Date: _______