Improving Glycemic Control and Clinical Outcomes in DM2 Patients in the Ambulatory Setting, a Pilot Study
Phase: NA
Conditions: Diabetes Mellitus
Sponsor: University of Maryland, Baltimore

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
COVER PAGE  
“improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
Introduction  
PI: Ilias Spanakis 
NCT 04800471 
Date: 02/26/2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
 
 
 
 
 
“improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
Introduction  
 
Managing patients with type 2 diabetes mellitus (T2DM) bears considerable challenges, as 
precise glucose monitoring and adherence to insulin therapy are necessary to guide therapeutic 
interventions. Although novel technological solutions such as automated insulin closed-loop 
delivery systems are available, many patients are treated with multiple daily insulin (MDI) 
regimens  and use point-of-care (POC) fingerstick testing for glucose monitoring. POC testing is 
a relatively painful method with multiple limitations, including insufficient glucose information, lack 
of compliance, and potential errors (e.g., handwritten logs). In addition, obtaining accurate 
information on insulin administration is hindered by the prevalent use of traditional insulin pens. 
Consequently, when making treatment decisions, healthcare professionals (HPC) often rely on 
self-reported glucose values and the assumption that patients adhere to treatment plans. 
Unfortunately, insulin adherence among patients with T2DM is problematic, and many patients 
have poor compliance with insulin therapy. 
 
Recent advancements in diabetes technology offer patients and HCPs efficient and reliable 
alternatives for obtaining glucose metrics and monitoring compliance. Continuous Glucose 
Monitoring (CGM) devices provide a sophisticated method of tracking glucose levels, gathering 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
high volumes of data continuously and automatically at frequent intervals. Additionally, Smart 
Insulin Pens (SIPs) record the timing and dosage of insulin, therefore documenting adherence.  
Utilizing software applications, data recorded by CGM and SIPs can then be shared with clinicians 
through Bluetooth and Internet connectivity.  
 
Lifestyle intervention is also an essential component of diabetes treatment and  managing patients 
with T2DM successfully involves promoting physical activity (PA). Increasing PA is associated 
with improved glycemic control, decreased risk of cardiovascular disease, and lower mortality. 
Despite its importance, most patients with T2DM remain physically inactive.   
 
Optimizing glycemic control requires, however, frequent outpatient clinic visits for medication 
adjustments. Given that over 38 million Americans live with diabetes and approximately 90-95% 
of them have T2DM , managing such a high volume can be challenging through traditional face-
to-face clinic visits.  Additionally, many patients with T2DM have underlying comorbidities that 
restrict mobility or live in remote areas, posing barriers to seeking in-person care. Telemedicine 
can serve as an alternative method of providing less time-consuming and more accessible patient 
care, allowing quicker titration of DM medications and improving monitoring and compliance in 
medication taking. However, most patients continue to be seen through face-to-face visits, and 
previously described telemedicine systems are limited by POC testing and traditional insulin 
pens.  
 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
With this study, we will perform a pilot randomized control trial (RCT) to examine the effectiveness 
and feasibility of a novel integrative telemedicine system for patients with T2DM, which combines 
CGMs, SIPs , official consultation from an exercise physiologist to promote PA and use of 
telecommunication methods. 
 
Description of the Integrated Telemedicine Model   
Our integrated telemedicine system is described below. First, to obtain glucose/insulin data, we 
will use a) CGM devices (Dexcom G6) and b) SIPs (Medtronic InPens for short-acting insulin and 
Insulclock Caps for long-acting insulin. Insulclock data will only be used for recording compliance 
and not for treatment decisions). Using Bluetooth technology and software applications, glucose, 
and insulin data from CGMs and SIPs will be sent to patients' smartphones, allowing them to 
make the recommended treatment decisions (e.g., prevent hypoglycemia, extra-correction insulin 
for hyperglycemia treatment, among others). Next, using program applications (i.e., Dexcom 
Clarity, Medtronic InPen), CGM/SIP reports will be generated to provide information relating to 
insulin nonadherence and patterns of hypo-hyperglycemia. Finally, HCPs will review the 
generated reports through commercial internet or Wi-Fi and use telecommunication systems (i.e., 
VA Video Connect (VVC), secure messaging (SM), or telephone call) to communicate with the 
patients and provide treatment recommendations. Additionally, during these telemedicine visits, 
an exercise physiologist (EP) will meet with participants remotely every three months. At the first 
EP appointment, a personalized and evidence-based PA  prescription will be developed using 
information provided by the subjects to carry out the prescription (e.g., tips for making time to stay 
active and referral to technical instruction videos). In subsequent follow-up telemedicine visits, EP 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
provider will give personalized feedback on successes and challenges with performing PA and 
T2D behavioral skills. 
 
Patient Population-Study Procedures 
 
In this prospective, randomized control pilot study will be conducted at the Baltimore VA Medical 
Center (BVAMC), 30 patients with T2DM will be enrolled.  Subjects who met at least one inclusion 
and none of the exclusion criteria defined below they will participate after they signed an informed 
consent.  
Inclusion Criteria: 
Insulin-treated patients with DM2 (treated with basal-bolus insulin regimens (MDI), ± non-insulin 
medications) and Uncontrolled glycemic control 
 
Exclusion Criteria: 
• 
History of type 1 DM (DM1) 
• 
Pregnant Patients 
• 
Extensive skin changes/disease or allergies that preclude wearing the CGM sensor 
• 
Subjects who have end-stage renal disease requiring dialysis 
• 
Significant psychiatric illness or any other condition rendering the subject incapable of 
understanding the objectives and potential consequences of the study 
 
Participants will be randomly assigned using a computer-generated random sequence at a 1:1 
ratio to either the Telemedicine group or the Standard of Care (SoC) group. All participants will 
be followed for six months, unless they died or if they withdrew consent and decided not to 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
continue participating in the study. No sample size calculations are provided due to the pilot 
nature of this study. Instead, we used a convenience sample of 30 subjects. This study was 
approved by the BVAMC IRB Committee. 
Following consent, subjects in both groups will have a baseline research visit where they will be 
placed on a ("blinded") Dexcom G6 CGM device for ten days to obtain baseline CGM glucose 
data. A baseline assessment of PA will be obtained by completion of the Senior Fitness test. 
Subjects will be then randomized to either Telemedicine or the Standard of Care (SoC).  
Participants in the telemedicine group will be educated about the appropriate use of the 
telemedicine system components. They will be asked to use their CGMs for ongoing 
automatic glucose monitoring, SIPs for insulin administration with recording insulin use, 
software applications, and VVC, SM, and telephone for telemedicine visits. Participants 
in the SoC will receive diabetes education as per standard of care (i.e., frequency of POC 
checking and proper insulin administration, among others). They will be asked to use 
POC for glucose monitoring and traditional insulin pens for insulin administration, and 
they will be asked to document POC, and insulin use as per standard of care. 
Then, following the initial baseline visit, patients in the Telemedicine group will have the 
following interventions: 
 
i)  in-person (Initial) Clinic Visit (Day 0):  

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
This will be a typical in-person clinic visit. Vital signs, medications, and a medical history 
will be obtained. POC values will be reviewed, and DM medication adjustments will be 
performed. CBC, BMP, HbA1c, and urine creatinine/microalbumin will be obtained per 
usual care. 
ii) Telemedicine visits (~every three weeks until +180 days [end of RCT]): 
Approximately every three weeks, patients will have remote visits using the DAT clinic. 
HCPs obtained CGM and SIP data using software applications (as above). Trends of 
hyperglycemia and hypoglycemia and their relationship with insulin administration will be 
identified, leading to adjustments of diabetes medications (insulin or non-insulin). 
Communication will be done by VVC, SM, or by phone. Patients will be evaluated more 
(i.e., if acute changes are needed after hypoglycemic events) or less frequently (i.e. if no 
changes on medications are needed). At the last remote visit (+180 days), all patients will 
have repeat lab work of CBC, BMP, HbA1c, and urine creatinine/ microalbumin. 
iii) Consultation (telecommunication) by an exercise physiologist (Days 0, +90 days, +180 
days [end of RCT]):  
On day 0, the exercise physiologist will evaluate baseline PA data and medical history, 
telecommunicate with each participant regarding their PA goals, facilitators, and barriers, 
and will write a PA prescription (frequency/intensity/duration/type) following best practices 
64. On days +90 and +180, he will discuss progress, set motivational intermediate goals 
to reach the long-term PA prescription objectives, and will modify exercises as needed. 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
iv)  Research Visit: At +180 days (end of RCT): 
Subjects will be placed on a "blinded" CGM. After ten days, Veterans will be asked to 
return the CGM, which will be downloaded. Subjects will complete the Senior Fitness 
test  for PA evaluation. 
Following the initial baseline visit, subjects  in the SoC group will have  the following 
interventions: 
i) One in-person (Initial) Clinic Visit (Day 0):  
This visit will be identical to the in-person visit that subjects will be randomized to the 
Telemedicine group had on Day 0.  
ii) Two in-person Clinic Visits (Day +90, +180):  
Subjects will have  a typical clinic in-person visit. Vital signs and HbA1c will be obtained, 
physical examinations will be performed, and POC values (either by report, logbook, or 
glucometer) will be reviewed. Information regarding insulin use and adherence will be 
obtained through patient reporting. DM medication adjustments will be performed, and 
patients will be instructed to increase their PA as clinically indicated. 
iii) One Research Visit: This visit will be at +180 days (end of RCT) and will be identical 
to the research visit of the Telemedicine clinic group. 
 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
Outcome Measures 
The purpose of this trial will be to examine the feasibility of the above interventions (CGMs, SIPs, 
Telecommunication systems and promoting PA by EP) combined as a single telemedicine 
intervention and examine whether it can lead to improvement in hyperglycemia, as defined by a 
decrease in HbA1c (primary outcome). Secondary outcomes will be time in range (TIR) 70-180 
mg/dL, time below range (TBR) <70 mg/dL, TBR <54 mg/dl, time above range (TAR ≥180 mg/dL 
and TAR≥250 mg/dl. In addition, we will evaluate differences in hypoglycemic events (CGM 
glucose <70 mg/dL for at least 15 minutes), clinically significant hypoglycemic episodes (CGM 
glucose< 54mg/dL for at least 15 minutes), and nocturnal hypoglycemia. For glucose variability, 
we will evaluate if there is a difference in the Coefficient of Variation (CV).  
STATISTICAL ANALYSIS 
Student's t-test will be used to compare baseline characteristics of the two groups. For 
continuous outcome measures (e.g., HbA1c, time <54 mg/dl, etc.), we will use linear 
regression analyses (SAS proc genmod with a normal distribution and identity link). For 
outcome measures that will be counts (e.g., number of hypoglycemic episodes <54 
mg/dl), we will use Poisson regression (SAS proc genmod with a Poisson distribution and 
a log link). Regardless of the type of regression we will use, the model will be change in 
outcome= baseline value + group + time + group + time where group will be control or 
telemedicine and time will be baseline, three-month, or six-month. We will calculate 
estimated values at each time point using the mean value of the outcome at baseline, 
baseline value, (SAS LSMeans statement with a pdiff option). Comparisons of baseline 

“Improving Glycemic Control in DM2 Patients in the Ambulatory Setting” 
PI Ilias Spanakis 
NCT04800471 
 
 
characteristics will be performed using Student's t-test. A two-tailed P ≤ 0.05 will indicate 
significance.