Validation Study for the Alertgy Non-invasive Continuous Glucose Monitor
Conditions: Type 2 Diabetes
Sponsor: The Cleveland Clinic

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Validation study for the Alertgy non-invasive continuous glucose monitor (ANICGM) 
 
Investigators 
M. Cecilia Lansang, MD, MPH (Professor of Medicine, endocrinology staff) 
Lauren Buehler, MD, MPH (endocrinology fellow) 
 
Study sponsor  
Cleveland Clinic Innovations 
 
External personnel 
Required to set up the device: 
Marc Rippen – CEO of Alertgy 
Ryan Bailey - Director of Engineering of Alertgy   
 
Introduction 
Diabetes mellitus (DM) affects 30 million people in the United States. To achieve glucose control, 
most patients are prescribed glucose meters by their physicians. Obtaining glucose levels in this 
manner necessitates cleaning the fingers, attaching a lancet to a device (or simply using a lancet 
if a device is not available), pricking the finger with a lancet, placing a drop blood on a strip, and 
awaiting the readout that results after some chemical reactions.  Thereafter, the lancet has to be 
disposed of in a safe receptacle and the finger has to be blotted to stop the blood from oozing. 
The anxiety, pain, and tedious process have led researchers to develop other means of checking 
glucose levels.  There are now continuous glucose monitoring systems (CGMS) that entail 
inserting a subcutaneous sensor that sends readings through a transmitter.  These CGMs may 
or may not need calibration with a fingerstick glucose reading, and the subcutaneous sensor still 
has to be changed every 10 -14 days.  
The Alertgy non-invasive continuous glucose monitor (ANICGM) is a device that does not entail 
any subcutaneous insertion of a sensor. It is strapped on to the wrist, and glucose readings are 
given based on subcutaneous signals (see Description of technology and Description of device 
below).  In 2001, a non-invasive device called Glucowatch Biographer was introduced that also 
involved subcutaneous signals without needing a subcutaneous insertion. However, for various 
reasons such as long calibration period and reading inaccuracies, the product did not take off.  
The ANICGM is a promising device that might overcome the limitations of existing and previous 
methods of non-invasive glucose measurement.  
  
 

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General aim 
This study aims to validate the glucose readings taken from the ANICGM with an approved 
outpatient glucose meter in patients with type 2 diabetes  
Specific aim 
1) To determine the correlation between glucose readings using the ANICGM an AccuChek 
Inform II blood glucose meter in patients with type 2 diabetes at baseline and after 
ingestion of a glucose load throughout a complete glucose excursion 
 
-Rationale: a continuous glucose monitor needs to capture rapid postprandial glucose 
increases and returns to baseline levels 
 
2) To ascertain if the ANICGM calibration is maintained up to 14 days  
 
-Rationale: the ANICGM is being developed for use for multiple days  
 
Note: The results from the ANICGM meter will not be used to guide any aspect of the 
patient’s treatment course.  
Description of the technology 
The ANICGM uses a weak electromagnetic field generated by its wrist band sensor to look into 
the body to produce a spectrum that provides a measurement of blood glucose present in the 
wrist area of the body. The core sensing technology used is dielectric spectroscopy, and has been 
shown capable of measuring blood glucose, non-invasively, in a laboratory environment (1-3).  
The system uses proprietary and patented dielectric materials and signal processing to enhance 
performance in both selectivity and sensitivity for blood glucose measurement. 
Much like how a MRI uses a strong magnetic field and its interaction with the body to create a 
picture of what is inside, the ANICGM uses a safe weak low frequency radiofrequency field to 
take a picture of a person’s chemical spectrum, some of it specific only to blood glucose.  
The device sends and receives back signals from the wrist area that are used to generate a 
dielectric spectrum once every 6 seconds. This spectral data is stored on the device, and then 
downloaded wirelessly or through USB port to an Alertgy laptop. The POC BG using the Accuchek 
Inform II will be used to provide calibration values for the ANICGM every 5 minutes in mg/dL, 
during the calibration process. The POC BG levels will be entered into the Alertgy laptop and a 
proprietary calibration program will be used to analyze the spectral data collected and will 
generate a calibration algorithm. The Alertgy support team will provide the ANICGM data to 
compare to the POC BG data they collected concurrently during the tests. 
Description of the device  
The present band is about 5 inches long made out of inert plastic material. It is applied to the wrist 
area and adjusted to a snug fit.  All of the materials that make contact with the body are inert. A 
photo is included below.  

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(This is the current model. An improved version may be available at the time of the study).  
 
Cleveland Clinic staff will be trained by a written instruction manual in the application and use of 
the device by Alertgy staff on site. As the device is automated and noninvasive, it is anticipated 
that the training period will take no longer than two hours maximum.  
Preliminary data 
Data from Alertgy in the graph below shows testing of 8 subjects in their lab showing correlation 
between the ANICGM (y-axis) and the Abbott Freestyle Neo glucometer (x-axis). 
Of the 8 subjects, 3 had type 2 diabetes (2 of whom are on insulin), 2 had prediabetes, and 3 did 
not have prediabetes or diabetes. 
Pearson’s correlation was used, R2= 0.993. 
 

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Inclusion Criteria 
Type 2 diabetes on diet or on pharmacologic treatment for diabetes 
Hemoglobin A1c (HbA1c) 7.5-10.0%  
- below 7.5%, there may not be a demonstrable blood glucose spike 
- above 10.0%, subjects are more likely to be symptomatic from hyperglycemia and 
require treatment during the study 
Age 18-75 years old 
Exclusion Criteria 
Patients taking prandial insulin 
Fasting blood glucose by fingerstick <70 mg/dL or >250 mg/dL. Hypoglycemia <70 mg/dL will be 
treated according to clinic protocol.  
Pregnancy  
ESRD 
Decompensated or acute heart failure 
Medications that might cause false readings with glucose meters: acetaminophen, ascorbic acid, 
dopamine, maltodextrin, mannitol 
Conditions that limit the ANICGM such as lesions on the forearms  
Other conditions that the investigators deem will affect the conduct of the study 

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Protocol  
There are 3 study visits: Visit 1, Visit 2 (3-14 days after Visit 1) and Visit 3 (5-14 days after Visit 
1) 
Alertgy personnel will undergo the onboarding process utilized by CCF Innovations called 
Silkroad/Red Carpet. Personnel undergoing this process complete 8 Comet modules (code of 
conduct, corporate complains, HIPPA overview and HIPPA & IS Security Awareness, Emergency 
Management, Environment of Care, Patient Safety and Energy Savings). 
Study Calendar 
  
Visit 1 
Visit 2 
Visit 3 
  
Day 1 
3-14 days 
5-14 days 
Informed Consent 
X 
  
  
Inclusion/Exclusion 
X 
  
  
Medical History  
X 
  
  
Urine Pregnancy Test * 
X 
X 
X 
Vitals 
X 
X 
X 
Comorbidities 
X 
  
  
Adverse Events Assessment 
X 
X 
X 
Medication Review 
X 
X 
X 
Ingest GlucoCrush 
X 
X 
X 
Glucose Collection (Fingersticks) 
X 
X 
X 
*Women with childbearing potential 
For all study visits 
The timing of the fingerstick blood glucose checks outlined below are approximate, as there might 
be occasions where the fingerstick might not be performed at the exact minute specified (for 
example, patient needing to go to restroom, issues with the Accuchek Inform II glucose meter, 
etc). Every effort will be made to do the fingerstick at the specified time. 
Subject fasts overnight, then proceeds to Cleveland Clinic Main Campus Adult Endocrinology 
clinic at F20.  
Vital signs will be taken. 
Women with childbearing potential will have a urine pregnancy test before each study. 
Patients will be asked to bring diabetes medications (and related devices) if requiring injections) 
to F20.   
If a subject is on basal insulin, the subject will take the basal insulin as close to the usual time as 
possible. 

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A baseline fingerstick blood glucose (BG) will be taken using the clinic’s Accuchek Inform II 
glucose meter (time -60 min); this is needed to determine eligibility. 
If BG 70-150 mg/dL subject will hold their morning medications or delay taking their diabetes 
medication until after the procedure (except for basal insulin as above) upon instructions of the 
investigator. 
If BG 151-250 mg/dL, subject will take their diabetes medication at the usual time to prevent 
symptomatic hyperglycemia.  
The ANICGM will be placed on the wrist. Measurements from the ANICGM start immediately. 
There will be a period of 20 minutes to allow the ANICGM to stabilize to body temperature. 
Fingerstick BG will be repeated at time -30 min, -15 min, and 0 min for baseline validation. 
At time 0 min, subjects ingest 75 g oral glucose drink (GlucoCrush) 
For Visit 1:  
Since the ANICGM is using new technology that depends on calculating the slope of the 
fingerstick glucose change to individualize the calibrations, it is crucial to have frequent 
fingersticks during Visit 1 for the first hour after the glucose challenge (GlucoCrush). 
After the GlucoCrush, fingerstick BG will be done every 5 minutes for 2 hours. 
Other continuous glucose devices have done monitoring as frequently as this (see attachment, 
figure 7, from Choi H, Naylon J, Luzio S, Beutler J, Birchall J, Martin C, Porch A. Design and In 
Vitro Interference Test of Microwave Noninvasive Blood Glucose Monitoring Sensor. IEEE Trans 
Microw Theory Tech. 2015 Oct 1;63(10 Pt 1):3016-3025) 
 
For Visit 2 and Visit 3:  
Fingerstick BG will be taken every 15 minutes for 2 hours after ingestion of GlucoCrush 
Other continuous glucose devices have done monitoring as frequently as this (see attachment, 
figure 8, from Choi H, Naylon J, Luzio S, Beutler J, Birchall J, Martin C, Porch A. Design and In 
Vitro Interference Test of Microwave Noninvasive Blood Glucose Monitoring Sensor. IEEE Trans 
Microw Theory Tech. 2015 Oct 1;63(10 Pt 1):3016-3025) 
For all study visits 
Wrist device is removed after each study visit. In-between patients, either same or different day, 
the device will be cleaned by using Super Sani Cloth wipes, which are the disinfectants we have 
in the endocrine clinic (active ingredients: dimethyl ethylbenzyl ammouinum chloride, isopropyl 
alcohol) 
 
 

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Sample Size 
It is expected that 10-15 subjects will be enrolled, and that there will be up to 24 paired measures 
on Visit 1 (every 5 minutes for 2 hours), and 8 paired measures (every 15 minutes for 2 hours) 
each of the follow-up days.  If no errors on the Clarke error grid are observed (as in the preliminary 
data), the error rate based on the “rule of three”, will be constrained to be no more than 0.5% 
overall (based on 600 total measures), and no greater than 5% within subject (Jovanovic and 

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Levy, 1997).  Confidence limits for the agreement will depend on the within and between subject 
variability measures, so formal power calculations on this measure of agreement is not possible.  
Statistical analysis 
Agreement between glucose measures between systems will be evaluated graphically using 
Bland-Altman plots, and Clarke error grids.  Error rates from the Clarke error grid will be 
calculated, and 95% confidence limits will be calculated overall, by subject and by day within 
subject.  Similarly, limits of agreement from the Bland-Altman plots will be adjusted to account for 
repeated measures, as described by Bland and Altman (2007).  Analysis will be performed using 
SAS software (version 9.4; Cary, NC).   
Possible adverse effects 
The materials for the wrist band are inert and the potential for allergy is low. 
Fingersticks can cause pain and discomfort. 
The Accucheck Inform II needs a small drop of blood for each fingerstick. 
Ingesting GlucoCrush may cause high blood glucose if diabetes is not in optimal control   
Should a patient develop acute hyperglycemia with symptoms such as increased thirst/vision 
changes/headache, patients will be hydrated and assessed for the need for insulin. The F20 clinic 
has regular insulin and/or fast-acting insulin. 
As with any patient who comes to the clinic and develops hypoglycemia, a hypoglycemia protocol 
is in place for study participants. Signs and symptoms of hypoglycemia include, but are not limited 
to: weakness, restlessness, nervousness, hunger, and sweating. If a patient develops 
hypoglycemia during the study follow up period (defined as blood sugar < 70 mg/dL), he/she will 
be administered 4 oz. (120ml) of juice. If the patient is unable to consume carbohydrate sources 
by mouth, he/she will receive an intramuscular glucagon injection, which is readily available in the 
clinic. 
Due to the potential risk for hypo- and hyperglycemia during the study period, patients will be 
strongly encouraged to have assisted transportation to and from the visit. In the event that this is 
not possible, the investigators will assess the subjects individually which might include 
recommendations to check fingerstick blood glucose at home prior to the visit, taking glucose 
tablets, staying after the study for observation and fingerstick blood glucose checks. 
Compensation 
Each study participant will be compensated $300 for each completed visit, with a total potential 
to earn $900 if all three visits are completed.  
Informed Consent 
Written informed consent will be obtained from the subjects.  
 
 
 

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Relationship between Alertgy and Cleveland Clinic 
Cleveland Clinic, along with University Hospitals and JumpStart, is a founding partner in the 
Cleveland location of the Silicon Valley headquartered organization called PlugNPlay 
platform.  The company has a Cleveland location which opened in 2018 and is located at the 
Global Innovation Center (downtown Cleveland).   
Alertgy, was a company that was accepted into the first batch PlugNPlay companies.  Numerous 
meetings were held with Cleveland Clinic, Metro & University Hospitals to show the 
technology.  Subject Matter Experts were convened to learn more about the technology and 
provide feedback as to how the technology could be enhanced and used in the market. 
Cleveland Clinic (Innovations & Endocrinology and Metabolic Institute) and Alertgy agreed to work 
together to validate the effectiveness of the company’s initial noninvasive blood glucose 
monitoring wristband.  Cleveland Clinic will recruit 15 people to determine if the product 
characteristics are functioning and are reliable. 
Cleveland Clinic will be performing product viability and design work.  Additionally, Cleveland 
Clinic Innovations is performing market analytics, business plan development support and STTR 
application review support.   Cleveland Clinic is being compensated for their work.   
Alertgy is remunerating $57,000 to Cleveland Clinic for services.  Cleveland Clinic will also receive 
a convertible note from Alertgy for $23,000.  Should the proof of concept work validate that the 
technology works, Cleveland Clinic will exercise the convertible note.  If the testing proves that 
the device does not work, Cleveland Clinic will not exercise the note.    
References 
1. Park JH, Kim CS, Choi BC, Ham KY. The correlation of the complex dielectric constant 
and blood glucose at low frequency. Biosens Bioelectron. 2003 Dec 15;19(4):321-4 
2. Freer B. Feasibility of a wireless non-invasive glucose monitor. Department of electrical 
microelectronic engineering. Rochester Institute of Technology. Masters of Science 
thesis 2011 
3. Jovanovic BD, Levy PS.  A Look at the Rule of Three. The American Statistician. 
1997;51(2):137-9. 
4. Bland JM, Altman DG. Agreement between methods of measurement with multiple 
observations per individual. J Biopharm Stat 2007;17:571–582.  
5. Choi H, Naylon J, Luzio S, Beutler J, Birchall J, Martin C, Porch A. Design and In Vitro 
Interference Test of Microwave Noninvasive Blood Glucose Monitoring Sensor. IEEE 
Trans Microw Theory Tech. 2015 Oct 1;63(10 Pt 1):3016-3025