Telemedicine Monitoring of Nocturnal Incidents of Treatment-Requiring Hypoglycemia in Older Adults With Type 1 Diabetes Miletus - A Feasibility Study
Phase: NA
Conditions: Diabetes Mellitus, Type 1, Hypoglycemia
Sponsor: University of Southern California

 
1 
Version 1.1 
 
1 
 
2 
 
3 
 TELEMEDICINE MONITORING OF NOCTURNAL INCIDENTS OF TREATMENT-REQUIRING 
4 
HYPOGLYCEMIA IN OLDER ADULTS WITH T1DM (TELE-MONITOR T1DM) A FEASIBILITY STUDY 
5 
 
6 
 
7 
An observational feasibility study to determine if it is possible to implement an automated 
8 
system of daily remote monitoring of CGM data to identify and contact patients who are 
9 
having episodes of hypoglycemia and/or difficulty using their CGM device. 
10 
 
11 
Study Protocol 
12 
 
13 
 
14 
Version 1.1 
15 
06/08/2018 
16 
 
 
17 

 
2 
Version 1.1 
Table of Contents 
18 
CHAPTER 1: INTRODUCTION .......................................................................................................... 4 
19 
1.1 Background Information .................................................................................................................... 4 
20 
1.2 Continuous Glucose Monitoring ......................................................................................................... 5 
21 
1.3 Preliminary Studies ............................................................................................................................ 6 
22 
1.4 Summary of Study Rationale .............................................................................................................. 7 
23 
1.5 Study Objectives ................................................................................................................................ 7 
24 
1.5.1 Primary Objectives .............................................................................................................................. 7 
25 
1.5.2 Secondary Objectives ......................................................................................................................... 7 
26 
1.6 Study Synopsis ................................................................................................................................... 8 
27 
1.6.1 Study Design ....................................................................................................................................... 8 
28 
1.6.3 Eligibility ............................................................................................................................................. 8 
29 
1.6.4 Visit and Phone Contact Schedule ...................................................................................................... 8 
30 
1.6.5 Testing and Assessments: ................................................................................................................... 9 
31 
1.6.6 Main Outcome Measures ................................................................................................................... 9 
32 
1.6.7 General Considerations ...................................................................................................................... 9 
33 
CHAPTER 2: ELIGIBILITY CRITERIA AND ENROLLMENT .................................................................... 9 
34 
2.1 Study Population ............................................................................................................................... 9 
35 
2.2 Eligibility Criteria ............................................................................................................................... 9 
36 
2.1.1 Eligibility ............................................................................................................................................. 9 
37 
2.1.2 Exclusions ......................................................................................................................................... 10 
38 
2.1.3 Assessment of Eligibility ................................................................................................................... 10 
39 
2.3 Informed Consent ............................................................................................................................ 10 
40 
CHAPTER 3: STUDY VISITS ............................................................................................................ 10 
41 
3.1 Study Visits ...................................................................................................................................... 10 
42 
3.1.1 Baseline Visit ..................................................................................................................................... 10 
43 
3.1.2 Procedures at Post Baseline Study Visits .......................................................................................... 11 
44 
3.1.3 Daily Uploading of CGM Data to Tidepool ........................................................................................ 11 
45 
3.2 TeleMonitoring ................................................................................................................................ 11 
46 
CHAPTER 4:  DATA COLLECTION AND TESTING PROCEDURES ....................................................... 11 
47 
4.1 HbA1c .............................................................................................................................................. 11 
48 
4.2 Continuous Glucose Monitoring (CGM) ............................................................................................ 11 
49 
4.3 T1D REDEEM Diabetes Distress Questionnaire ................................................................................. 11 
50 
4.4 Hypoglycemia Fear Survey ............................................................................................................... 12 
51 
4.5 Simplified Diabetes Knowledge Test ................................................................................................ 12 
52 
4.6 Assessment of Severe Hypoglycemia and Diabetic Ketoacidosis ....................................................... 12 
53 
CHAPTER 5: MISCELLANEOUS CONSIDERATIONS ......................................................................... 13 
54 
5.1 Adverse Events and Risks ................................................................................................................. 13 
55 
5.1.1 Definition .......................................................................................................................................... 13 
56 
5.2 Recording of Adverse Events ............................................................................................................ 13 
57 
5.3 Reporting Serious Adverse Events and Unexpected Adverse Device Events ...................................... 14 
58 
5.3 Risks and Discomforts ...................................................................................................................... 15 
59 
5.3.1 Risk of Hypoglycemia and Hyperglycemia ........................................................................................ 15 
60 
5.3.2 CGM Sensor Placement .................................................................................................................... 15 
61 
5.3.3 CGM Sensor Inaccuracy .................................................................................................................... 15 
62 
5.3.4 Skin Reactions ................................................................................................................................... 15 
63 
5.3.5 Fingerstick HbA1c and Blood Glucose Measurements ..................................................................... 15 
64 
5.3.6 Psychosocial Questionnaires ............................................................................................................ 15 
65 

 
3 
Version 1.1 
5.3.7. Tele-Monitor .................................................................................................................................... 16 
66 
5.3.8 Loss of Privacy .................................................................................................................................. 16 
67 
6.0 MISCELLANEOUS CONSIDERATIONS ....................................................................................... 16 
68 
6.1 Benefits ........................................................................................................................................... 16 
69 
6.2 Participant Reimbursement ............................................................................................................. 16 
70 
6.3 Participant Withdrawal .................................................................................................................... 16 
71 
6.4 Confidentiality ................................................................................................................................. 16 
72 
CHAPTER 7: STATISTICAL CONSIDERATIONS ................................................................................. 17 
73 
7.1 Sample Size ...................................................................................................................................... 17 
74 
7.2 Statistical Analyses .......................................................................................................................... 17 
75 
CHAPTER 8: REFERENCES ............................................................................................................. 18 
76 
 
77 
 
78 
 
 
79 

 
4 
Version 1.1 
CHAPTER 1: INTRODUCTION 
80 
1.1 Background Information 
81 
Older adults with type 1 diabetes (T1D), a growing but under-evaluated population (1-4), are prone 
82 
to hypoglycemia and hypoglycemia unawareness, particularly when diabetes is longstanding. 
83 
Hypoglycemia, which in addition to producing altered mental status and sometimes seizure or loss 
84 
of consciousness, can be associated with falls leading to fractures, and cardiac arrhythmias resulting 
85 
in sudden death (5-7). Hypoglycemia must always be considered a possible contributing factor in 
86 
older adults with T1D in whom these events occur, especially when a glucose measurement is not 
87 
available from the time of the event (8). In Medicare beneficiaries with diabetes, hospitalizations 
88 
related to hypoglycemia are now more frequent than those for hyperglycemia and are associated 
89 
with high 1-year mortality (6). Emergency room visits due to hypoglycemia also are common (5). 
90 
These reports likely underestimate the risk of hypoglycemia in older adults with T1D since they 
91 
include individuals with the more prevalent type 2 diabetes in whom severe hypoglycemic events 
92 
are likely considerably less frequent than they are in individuals with T1D. 
93 
 
94 
Unlike treatment guidelines in younger individuals with T1D which focus on optimizing glycated 
95 
hemoglobin (HbA1c) levels, treatment approaches for older adults with T1D often focus on 
96 
minimizing hypoglycemia rather than attempting to achieve low HbA1c levels (9, 10). Despite these 
97 
efforts, biochemical hypoglycemia occurs frequently and severe hypoglycemia (SH) occurs more 
98 
often in older than younger adults with T1D. Data from the T1D Exchange registry has shown a 
99 
remarkably high frequency of SH in older adults with longstanding T1D: 18% of registry participants 
100 
>60 years old reported seizure or loss of consciousness due to hypoglycemia in the prior 12 months 
101 
(11). In addition, although there may be less of a push towards tight control in older adults, T1D 
102 
Exchange registry data indicate that SH is just as common with HbA1c levels >8.0% as it is for HbA1c 
103 
levels <7.0% (11). A T1D Exchange study (12) of 201 adults ≥60 years old with T1D duration ≥20 
104 
years (101 with SH in the prior year and 100 without SH in the prior 3 years) found that glucose 
105 
concentrations measured with blinded continuous glucose monitoring (CGM) were <70 mg/dL for a 
106 
median of 91 minutes per day and <50 mg/dL for 31 minutes per day. Furthermore, mean HbA1c 
107 
was similar in the individuals who had experienced SH in the prior year compared with those who 
108 
had not experienced SH in the prior 3 years (7.8% versus 7.7%). These data do not support the 
109 
strategy of “raising the HbA1c” an effective approach for hypoglycemia prevention in older adults 
110 
with T1D.  
111 
 
112 
Hypoglycemia unawareness, or the loss of physiological symptoms associated with a low blood 
113 
glucose level, is associated with duration of diabetes, making it particularly prevalent in older adults. 
114 
The presence of hypoglycemia unawareness is associated with a 20-fold increased risk for 
115 
experiencing SH (13). The prevalence of hypoglycemia unawareness was remarkably high in the T1D 
116 
Exchange of older adults (12), 147 with 58% of those with SH within the prior year having 
117 
hypoglycemic unawareness compared with 25% in those with no SH in the prior 3 years. 
118 
Furthermore, glycemic variability was significantly greater for those having experienced SH within 
119 
the prior year, supporting mechanisms beyond awareness of hypoglycemia contributing to risk for 
120 
SH in older adults with T1D.   
121 
 
122 
The occurrence of hypoglycemia and fear of hypoglycemia have adverse effects on quality of life of 
123 
both the individuals with T1D (14) and their families (15). Hypoglycemia fear and associated 
124 
behaviors impact participation in activities that are beneficial to emotional and physical well-being 
125 

 
5 
Version 1.1 
(e.g., exercise, socializing, and travelling), and may lead to intentional hyperglycemia. Diabetes-
126 
related distress (i.e., the emotions, stresses and worries associated with diabetes) is also an 
127 
important component of QOL for people with T1D and is associated with poor glycemic control, 
128 
longer duration of diabetes, higher rates of depression, and prior SH (16). 
129 
 
130 
Aging is associated with normative decline in cognitive functioning independent of any disease 
131 
process. Thus, older adults often have more difficulty learning and adopting new technologies and 
132 
following complex medication regimens. Older adults with T1D have additional risk for more 
133 
substantial cognitive impairment given increased rates of microvascular and macrovascular 
134 
complications from longstanding diabetes. We previously found that mild cognitive impairment is 
135 
common in community dwelling older adults with T1D (see preliminary data) and that it is related to 
136 
activities of daily living and everyday diabetes related tasks (17). Further, those with SH perform 
137 
poorer in some areas of cognitive function than those without SH (12) making it possible that 
138 
cognitive impairment increases the risk of a SH event. While it is possible that SH results in greater 
139 
cognitive impairment, this has not been supported in a younger T1D cohort in DCCT/EDIC followed 
140 
for over 18 years (18). The combination of cognitive difficulties and blunting of the alerting 
141 
symptoms of hypoglycemia may put older adults at high risk for hypoglycemia (19). 
142 
 
143 
1.2 Continuous Glucose Monitoring  
144 
CGM measures interstitial glucose concentrations and provides for real-time observation of glucose 
145 
levels, trend direction and alarms for when glucose drops to low levels. The components or CGM 
146 
include a receiver, a transmitter and a sensor. In December 2016, the FDA expanded the indications 
147 
for the Dexcom G5 sensor to allow for replacement of fingerstick blood glucose testing for diabetes 
148 
treatment decisions.  
149 
 
150 
Several randomized trials have demonstrated the efficacy of CGM when it is used on a regular basis 
151 
by individuals with T1D, particularly adults (20-23). Among individuals with HbA1c levels above 
152 
target, improvement has been demonstrated in HbA1c levels and in a reduction in biochemical 
153 
hypoglycemia. Among individuals with HbA1c levels at or below target, CGM has been 
154 
demonstrated to reduce biochemical hypoglycemia while at the same time maintaining excellent 
155 
HbA1c levels better than a control group (24). While these trials have found consistent glycemic 
156 
benefit with CGM use, it is clear that the amount of benefit is related to the amount of CGM use 
157 
(22, 23).  
158 
  
159 
In addition, regular CGM users have reported substantial satisfaction with use of the device and 
160 
improved QOL (25). The JDRF funded RCT of CGM in children and adults showed a modest 
161 
improvement in hypoglycemia fear associated with CGM use in the adult cohort, but no changes in 
162 
other more general measures of QOL (23). Langendam et al. found no benefit of continuous glucose 
163 
monitoring on QOL in their Cochrane Review, although only 5 of 22 studies included QOL outcomes 
164 
(26). However, all of these studies used earlier generation CGM devices. Based on the extremely 
165 
high compliance with daily CGM use in recently completed trials coordinated by the Jaeb Center for 
166 
Health Research using the Dexcom G4 or G5 sensor, substantially higher patient satisfaction and 
167 
improvement in QOL is likely with the current generation Dexcom device.  
168 
 
169 
CGM can alert when blood glucose is low or trending downward and this information can be 
170 
automatically shared with others; features that may be particularly helpful for those at risk for SH. 
171 

 
6 
Version 1.1 
Polonsky and Hessler surveyed existing CGM users and found that older age was associated with a 
172 
greater perceived benefit in hypoglycemia safety and interpersonal support, although the mean age 
173 
of this sample was 41 years (25). Despite its potential benefits to reduce hypoglycemia and 
174 
hypoglycemia fear, CGM is used by only a small proportion of older adults with T1D. In the T1D 
175 
Exchange registry, only 19% of adults over the age of 60 are using CGM, a percentage that likely 
176 
over-represents CGM use in this age group since all of the registry participants, by selection, are 
177 
seen by an endocrinologist who has a practice focused on T1D. 
178 
 
179 
1.3 Preliminary Studies  
180 
The USC research team has experience in conducting CGM and hypoglycemia studies in older adults 
181 
with T1D. They were part of study funded by the T1D Exchange Clinic Network which was a case-
182 
control study of 201 individuals >60 years old with T1D for ≥20 years at 18 clinical sites (12). The 
183 
objective of the study was to assess potential contributory factors for the occurrence of severe 
184 
hypoglycemia, including cognitive functioning, social support, depression, hypoglycemia 
185 
unawareness, various aspects of diabetes management, residual insulin secretion (as measured by 
186 
C-peptide levels), frequency of biochemical hypoglycemia, and glycemic control and variability. 
187 
Cases (N=101) had at least one severe hypoglycemic event in the prior 12 months while controls 
188 
(N=100), frequency-matched to cases on age, had no severe hypoglycemia in the prior 3 years. 
189 
HbA1c levels (mean 7.8% versus 7.7%) and CGM-measured mean glucose (175 mg/dL versus 175 
190 
mg/dL) were similar between cases and controls. More cases than controls had hypoglycemia 
191 
unawareness; only 11% of cases compared with 43% of controls reported always having symptoms 
192 
associated with low blood glucose levels (p<0.001). Cases had greater glucose variability than 
193 
controls (p=0.008) and experienced CGM glucose levels <60 mg/dL more often than in controls 
194 
(p=0.04). Cases scored worse than controls on measures of general mental status, processing speed 
195 
and executive functioning. As expected, hypoglycemia fear was higher in cases compared with 
196 
controls.  
197 
 
198 
In this sample of non-demented, community dwelling and functionally independent older adults 
199 
with T1D, 55% of the combined sample was at least mildly impaired (compared to demographically 
200 
corrected normative data) on a brief neuropsychological test battery, with 35% in the moderate to 
201 
severely impaired range. This was clinically relevant, as cognitive performance was associated with 
202 
simulated diabetes task performance (e.g., calculating an insulin dose based on a nutritional label) 
203 
and instrumental activities of daily living (17). Due to the cross-sectional nature of this work, 
204 
however, it is not known if cognitive impairment is a cause or consequence (or both) of 
205 
hypoglycemia. In those with mild or moderate cognitive impairment, falling glucose alert and 
206 
threshold alarm features of CGM may be particularly useful to “remind” patients to check their 
207 
blood glucose when the glucose level is decreasing and approaching the hypoglycemic range.  
208 
 
209 
Additionally, we are investigators on the WISDM Trial, which is a multi-center study on the use of 
210 
CGM in individuals with type 1 diabetes who are 60 years of age and older.  It is an RCT in which 
211 
patients are randomized to CGM vs. no CGM for 6 months and then all participants will wear a CGM 
212 
for the second 6 months of the study. 
213 
 
214 

 
7 
Version 1.1 
1.4 Summary of Study Rationale  
215 
Reducing hypoglycemia is an important aspect of management of T1D in older adults, many of 
216 
whom have hypoglycemic unawareness, cognitive impairment, or both. CGM offers the opportunity 
217 
to reduce hypoglycemia and its related complications such as fractures from falls and 
218 
hospitalizations and improve QOL including reducing hypoglycemic fear and diabetes distress. 
219 
Despite these potential benefits, CGM is used by only a small proportion of older adults with T1D 
220 
(19% in the T1D Exchange registry). Previous studies assessing CGM efficacy have included only a 
221 
small number of adults ≥ 60 years of age, excluded patients most prone to SH, focused on improving 
222 
HbA1c rather than hypoglycemia, and used older generation CGM sensors. These studies are not 
223 
generalizable to the population of older adults with T1D. The potential benefit of CGM in reducing 
224 
hypoglycemia in the older adult population has not been well studied. Prior and on-going trials 
225 
compare CGM to self-monitoring of blood glucose levels, but none look at remote daily monitoring 
226 
of CGM data.  Moreover, in none of the studies is education standardized.  The follow-up of patients 
227 
is done only at routine clinic visits, without any particular oversight of glucose values on an on-going 
228 
basis.  In some cases individual patients may share their data with a family member, but these are 
229 
generally not trained medical personnel and the Dexcom provided by Medicare has the “share” 
230 
feature disabled. 
231 
 
232 
1.5 Study Objectives  
233 
1.5.1 Primary Objectives  
234 
Primary Aim 1: To determine the effect of continuous remote CGM reporting coupled with a 
235 
telemedicine intervention (Tele-CGM program) on rates of hypoglycemia in adults with T1D >65 
236 
years old. 
237 
Working Hypothesis: Participants using the Tele-CGM program will have a reduction in 
238 
hypoglycemia (as measured by the amount of time spent with glucose both below 54 mg/dl and in 
239 
the range of 54-70 mg/dl) compared with participants followed in usual care using CGM. 
240 
1.5.2 Secondary Objectives 
241 
Secondary Aim 1: To determine the effect of the Tele-CGM program on rates of CGM adherence and 
242 
successful use in adults with T1D >65 years old. 
243 
Working Hypothesis: Participants using the Tele-CGM program will have an increase in weekly time 
244 
spent wearing functional CGM devices compared with participants followed in usual care using 
245 
CGM.  This should improve CGM-based outcomes due to the relationship between CGM weekly 
246 
utilization and CGM benefits. 
247 
Secondary Aim 2: To determine the effect of the Tele-CGM program on quality of life (as measured 
248 
by reduction in hypoglycemic fear and improved diabetes specific distress, emotional wellbeing, and 
249 
ratings of global health), in adults with T1D > 65 years of age. 
250 
Working Hypothesis: Participants using the Tele-CGM program will have an improved quality of life 
251 
compared with participants followed in standard care without it. 
252 

 
8 
Version 1.1 
Secondary Aim 3:  To determine the effect of the Tele-CGM program on costs for the care of adults 
253 
with T1D >65 years old. 
254 
 Working Hypothesis: Participants using the Tele-CGM program will have a reduction in the need for 
255 
emergency department or urgent clinic visits, as well as paramedic services.  Telemedicine visits and 
256 
automated remote monitoring are much less expensive and potentially more effective than in-
257 
person visits. 
258 
Additional Secondary and Exploratory Aims: Secondary analyses of CGM data will be performed to 
259 
look for patterns and trends will to assess whether changes in metrics such as glucose variability or 
260 
time in range can predict episodes of hypoglycemia. Rates of SH events, ER visits, hospitalizations, 
261 
falls, and fractures will be assessed. The study will provide the opportunity to explore factors that 
262 
may mediate or moderate the relationships between CGM glucose levels and study outcomes, 
263 
including method of insulin administration (pump versus injection), presence of cognitive 
264 
impairment, frailty, hypoglycemic unawareness, glycemic variability, and scores on baseline and 
265 
subsequent QOL and cognitive function measures. 
266 
1.6 Study Synopsis 
267 
1.6.1 Study Design 
268 
This study is a single center pilot study 
269 
 
270 
1.6.2 Sample Size: 10 subjects  
271 
1.6.3 Eligibility  
272 
1) Diagnosis of type 1 diabetes  
273 
2) Age >65 years old 
274 
3) No serious illnesses where life expectancy is <1 year  
275 
4) Insulin regimen involves either use of an insulin pump or multiple daily injections of insulin.  
276 
5) Understand the study requirements and agree to comply with all study visits and procedures, 
277 
including the use of the study CGM. 
278 
6) Fluent in English or Spanish 
279 
7) Must have a smart phone 
280 
1.6.4 Visit and Phone Contact Schedule 
281 
Participants from our clinic population who fit the entry criteria will be asked to join the study. 
282 
 
283 
Baseline Visit—Visit 0 
284 
1.  Obtain informed consent 
285 
2.  Administer questionnaires 
286 
3.  Measure point of care A1C 
287 
4.  Start study Dexcom CGM device (those already on CGM will change to the study device). 
288 
5.  The patient will be signed into Tidepool using a research code name and email. 
289 
 
290 
Visit 1—2 weeks 
291 
1.  14 days worth of data will be downloaded from the patient’s CGM device. 
292 
2.  Systems will be checked to be sure they are functioning 
293 
3.  Remote monitoring program will be activated. 
294 

 
9 
Version 1.1 
4.  Telemedicine procedure will be discussed with patient; emergency contact numbers will be 
295 
obtained in case patient cannot be reached 
296 
 
297 
Visit 2—14 weeks 
298 
1.  Administer questionnaires 
299 
2.  Measure point of care A1C.  
300 
3.  Collect CGM data and compare to baseline 
301 
1.6.5 Testing and Assessments:  
302 
• Continuous glucose monitoring (CGM) 
303 
• Tidepool cloud upload 
304 
• Laboratory testing:  Point of care HbA1c  
305 
• Telemedicine outreach 
306 
• T1D REDEEM diabetes distress questionnaire 
307 
• Hypoglycemia Fear Survey 
308 
• Assessment of Severe Hypoglycemia and Diabetic Ketoacidosis 
309 
1.6.6 Main Outcome Measures  
310 
Primary Outcome: Rates of hypoglycemia 
311 
Second Outcome:  Adherence to CGM 
312 
Secondary Outcome: Changes in quality of life (as measured by reduction in hypoglycemic fear and 
313 
improved diabetes specific distress, emotional wellbeing, and ratings of global health) 
314 
Secondary Outcome:  Change in A1C 
315 
Secondary Outcome:  Change in time in range 
316 
1.6.7 General Considerations 
317 
The study is being conducted in compliance with the ethical principles that have their origin in the 
318 
Declaration of Helsinki and with the standards of Good Clinical Practice.  
319 
 
320 
 
321 
CHAPTER 2: ELIGIBILITY CRITERIA AND ENROLLMENT 
322 
2.1 Study Population 
323 
Participants in the study must meet criteria as described below.   
324 
2.2 Eligibility Criteria 
325 
2.1.1 Eligibility  
326 
1) Diagnosis of type 1 diabetes  
327 
2) Age 65 - 75 years old 
328 
3) No serious illnesses where life expectancy is <1 year  
329 
4) Insulin regimen involves either use of an insulin pump or multiple daily injections of insulin.  
330 

 
10 
Version 1.1 
5) Understand the study requirements and agree to comply with all study visits and procedures, 
331 
including the use of the study CGM. 
332 
6) Fluent in English or Spanish 
333 
7) Use of an iPhone that can stream data into Tidepool 
334 
2.1.2 Exclusions 
335 
1) Subject anticipates the need to use Tylenol or other pain-relieving medications containing 
336 
acetaminophen. 
337 
2) Subject is currently pregnant or lactating or plan on becoming pregnant during the course of the 
338 
study.   
339 
3) Subject is blind 
340 
4) Subject cannot follow instructions due to a medical condition or mental illness.  
341 
5) Subject has a known allergy to medical adhesive. 
342 
2.1.3 Assessment of Eligibility 
343 
Eligibility will be assessed as part of usual care and review of clinic records. 
344 
 
345 
2.3 Informed Consent 
346 
Individuals who are interested in participating in this study must be willing to sign a written consent 
347 
in order to participate.  
348 
 
349 
 
350 
CHAPTER 3: STUDY VISITS 
351 
3.1 Study Visits   
352 
Study visits will occur at  
353 
• Baseline 
354 
• 14 days (+3 days)  
355 
• 14 weeks (+7 days)  
356 
 
357 
Additional office visits may occur as needed. 
358 
3.1.1 Baseline Visit 
359 
After informed consent is obtained, the following will be done: 
360 
1) Information will be collected from the chart and solicited from the participant with respect 
361 
to: emergency contact information, medications, medical conditions, physical exam, 
362 
management, demographics, exercise, nutrition, insulin use, and other diabetes 
363 
management factors.  
364 
2) HbA1c  
365 
3) Questionnaires: 
366 
• T1D REDEEM diabetes distress questionnaire 
367 
• Hypoglycemia Fear Survey 
368 
• Simplified Diabetes Knowledge Test 
369 
• Assessment of Severe Hypoglycemia and Diabetic Ketoacidosis 
370 
4) CGM device will be provided and sensor will be inserted and instructions on calibration, use, 
371 
and maintenance issues will be provided 
372 
5) Tidepool account set-up and training 
373 

 
11 
Version 1.1 
3.1.2 Procedures at Post Baseline Study Visits  
374 
The following procedures will be performed at each visit, unless otherwise specified:  
375 
• Assessment of compliance with CGM  
376 
• Solicitation of the occurrence of adverse events, including falls, hospitalizations, emergency 
377 
department visits, severe hypoglycemia, and diabetic ketoacidosis  
378 
• Assessment of device issues  
379 
• CGM skin assessment  
380 
• Review of glucose data and insulin dosing and recommendations for changes in diabetes 
381 
management  
382 
• HbA1c determination using a point of care device at 14 weeks 
383 
3.1.3 Daily Uploading of CGM Data to Tidepool 
384 
CGM data will automatically upload to the Tidepool system through the subject’s existing iPhone via 
385 
the iPhone Health app. 
386 
3.2 TeleMonitoring  
387 
This will consist of an out going call/email to the patient if one of the following occur has occurred in 
388 
the past 24 hours:  ≥4 hours without CGM signal, ≥2 hours 54 – 70 mg/dl and/or 15 minutes <54 
389 
mg/dl.  The study coordinator will be alerted each morning though the Tidepool program to patients 
390 
who fit these criteria.  The outgoing call/email will consist of questions to find out why the event 
391 
happened and then suggestions on how to trouble shoot to avoid issues in the future.  If needed the 
392 
participant will be seen in person for an education/training session. 
393 
 
394 
If the patient cannot be reached within 6 hours, the patient’s emergency contact will be notified if 
395 
the PI feels that such out reach is warranted. 
396 
 
397 
 
398 
CHAPTER 4:  DATA COLLECTION AND TESTING PROCEDURES 
399 
4.1 HbA1c 
400 
HbA1c will be obtained using the point of care Siemens DCA Vantage Analyzer at Baseline, and at 14 
401 
weeks. 
402 
4.2 Continuous Glucose Monitoring (CGM) 
403 
A commercially available DexCom G5 or G6 CGM device will be provided and a sensor will be 
404 
inserted.  The participant will receive instructions on calibration, insertions, maintenance, use, and 
405 
removal of the sensor. 
406 
4.3 T1D REDEEM Diabetes Distress Questionnaire 
407 
The T1D REDEEM Diabetes Distress Questionnaire (9) measures several dimensions of stress related 
408 
to having type 1 diabetes. It consists of the following 7 subscales: Subscale 1 - Powerlessness (5 
409 
items); Subscale 2 – Management Distress (4 items); Subscale 3 – Hypoglycemia Distress (4 items); 
410 
Subscale 4 – Negative Social Perceptions (4 items); Subscale 5 – Eating Distress (3 items); Subscale 6 
411 
– Physician Distress (4 items); Subscale 7 – Friend/Family Distress (4 items). Each question has a 6-
412 
choice Likert response format. Administration time is approximately 10 minutes. 
413 

 
12 
Version 1.1 
4.4 Hypoglycemia Fear Survey 
414 
The Hypoglycemia Fear Survey measures several dimensions of fear of hypoglycemia among adults 
415 
with type 1 diabetes (10).  It consists of a 10-item Behavior subscale that measured behaviors 
416 
involved in avoidance and over-treatment of hypoglycemia and a 13-item Worry subscale that 
417 
measures anxiety and fear surrounding hypoglycemia, each with a 5-choice Likert response format.  
418 
Administration time is approximately 10 minutes. 
419 
4.5 Simplified Diabetes Knowledge Test 
420 
The Simplified Diabetes Knowledge Test (11) consists of 23 knowledge test items developed by the 
421 
Michigan Diabetes Research Training Center (MDRTC). These items represent a test of general 
422 
knowledge of diabetes and are answered in a true/false/don’t know format. The psychometric 
423 
properties provide information regarding the reliability of the various groups of items, as well as a 
424 
difficulty index (percent of patients who scored this item correctly), and an item to group total 
425 
correlation for each item. These data can be reported when describing the use of the test. 
426 
Administration time is approximately 15 minutes.    
427 
4.6 Assessment of Sever Hypoglycemia and Diabetic Ketoacidosis 
428 
The Assessment of Severe Hypoglycemia and Diabetic Ketoacidosis is an interviewer administered 
429 
survey assessing if the subject had any episodes of severe hypoglycemia and/or diabetic 
430 
ketoacidosis since their last study visit. Events are recorded to assess frequency, as is type of 
431 
assistance required to treat the event. Administration time is approximately 5 minutes. 
432 
 
433 
4.7 Tidepool.  https://tidepool.org/ 
434 
Tidepool is an open source, not-for-profit company focused on “liberating data from diabetes 
435 
devices, supporting researchers, and providing free software to people with diabetes and their care 
436 
teams.”  Tidepool is the program that is used routinely in our clinic to assess data from diabetes 
437 
devices. As part of clinical care all patients are encouraged to upload their data to Tidepool for 
438 
analysis. Currently we have over 250 patients streaming data into Tidepool.  However, data is not 
439 
analyzed on a daily basis, but rather on as “as needed” basis if a patient contacts the clinic with a 
440 
problem. 
441 
 
442 
Tidepool is an open source platform because they want to catalyze innovation, so they make their 
443 
code and designs openly available. They also believe that the healthcare industry needs more 
444 
sharing and greater transparency, and being open source is one way to make a difference.  
445 
 
446 
Tidepool complies with all HIPAA privacy, security and breach notification regulations. Tidepool 
447 
enters into Business Associate Agreements (BAAs) with requesting clinics, and also has 
448 
subcontractor BAAs with our underlying technology service providers (e.g., Amazon Web Services 
449 
and Google). 
450 
 
451 
Tidepool is an FDA registered entity. The software is listed with the FDA under regulations 880.6310 
452 
and 862.2120 as Class I/Exempt medical devices and Medical Data Display Systems. Tidepool 
453 
complies with all applicable FDA regulations including 21 CFR 820 Quality System Regulations. Class 
454 
I/Exempt and MDDS software are exempt from FDA part 510(k) filing and approval requirements. 
455 
 
456 
 
457 

 
13 
Version 1.1 
CHAPTER 5: MISCELLANEOUS CONSIDERATIONS 
458 
5.1 Adverse Events and Risks 
459 
5.1.1 Definition  
460 
Reportable adverse events will include the following: severe hypoglycemia as defined below, 
461 
hyperglycemia/diabetic ketoacidosis (DKA) as defined below, all device-related events with 
462 
potential impact on participant safety, all falls or fractures, emergency room visits, and all events 
463 
meeting criteria for a serious adverse event. Skin reactions from sensor placement are only 
464 
reportable if severe and/or required treatment.  
465 
 
466 
Hypoglycemic events are recorded as Adverse Events only if the event required assistance of 
467 
another person due to altered consciousness, and required another person to actively administer 
468 
carbohydrate, glucagon, or other resuscitative actions. This means that the participant was impaired 
469 
cognitively to the point that he/she was unable to treat himself/herself, was unable to verbalize his/ 
470 
her needs, was incoherent, disoriented, and/or combative, or experienced seizure or coma. These 
471 
episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. If plasma 
472 
glucose measurements are not available during such an event, neurological recovery attributable to 
473 
the restoration of plasma glucose to normal is considered sufficient evidence that the event was 
474 
induced by a low plasma glucose concentration.  
475 
 
476 
Hyperglycemic events are recorded as Adverse Events if evaluation or treatment was obtained from 
477 
a 801 health care provider or if the event involved DKA, as defined by the Diabetes Control and 
478 
Complications Trial (DCCT), and had all of the following:  
479 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting;  
480 
• Serum ketones >1.5 mmol/L or large/moderate urine ketones;  
481 
• Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and 
482 
• Treatment provided in a health care facility  
483 
 
484 
In addition, hyperglycemia not meeting the definition of DKA will be reported as an adverse event if 
485 
emergency evaluation or treatment was obtained at a health care facility; these events are 
486 
considered Adverse Events and not Serious Adverse Events (SAE) unless one of the criteria for SAE is 
487 
met.  
488 
5.2 Recording of Adverse Events  
489 
Throughout the course of the study, all efforts will be made to remain alert to possible adverse 
490 
events or untoward findings. The first concern will be the safety of the study participant, and 
491 
appropriate medical intervention will be made.   
492 
 
493 
All reportable adverse events whether volunteered by the participant, discovered by study 
494 
personnel during questioning, or detected through physical examination, laboratory test, or other 
495 
means will be reported on an adverse event form. Since the goal of the study is to provide unique 
496 
daily monitoring, AE’s may be noted by the study coordinator before the patient would routinely 
497 
report them.  The study investigator reviews each adverse event form. 
498 
 
499 
The study investigator will assess the relationship of any adverse event to be related or unrelated by 
500 
determining if there is a reasonable possibility that the adverse event may have been caused by the 
501 

 
14 
Version 1.1 
study intervention. To ensure consistency of adverse event causality assessments, investigators 
502 
should apply the following general guideline when determining whether an adverse event is related:  
503 
 
504 
Yes  
505 
There is a plausible temporal relationship between the onset of the adverse event and the study 
506 
intervention, and the adverse event cannot be readily explained by the participant’s clinical 
507 
state, intercurrent illness, or concomitant therapies; and/or the adverse event follows a known 
508 
pattern of response to the study intervention; and/or the adverse event abates or resolves upon 
509 
discontinuation of the study intervention or dose reduction and, if applicable, reappears upon 
510 
re-challenge. 
511 
 
512 
No  
513 
Evidence exists that the adverse event has an etiology other than the study intervention (e.g., 
514 
pre-existing medical condition, underlying disease, intercurrent illness, or concomitant 
515 
medication); and/or the adverse event has no plausible temporal relationship to study 
516 
intervention.  
517 
 
518 
The intensity of adverse events will be rated on a three-point scale: (1) mild, (2) moderate, or (3) 
519 
severe. It is emphasized that the term severe is a measure of intensity: thus, a severe adverse event 
520 
is not necessarily serious. For example, itching for several days may be rated as severe, but may not 
521 
be clinically serious.  
522 
 
523 
Adverse events will be coded using the MedDRA dictionary.  
524 
 
525 
Adverse events that continue after the study participant’s discontinuation or completion of the 
526 
study will be followed until their medical outcome is determined or until no further change in the 
527 
condition is expected. 
528 
5.3 Reporting Serious Adverse Events and Unexpected Adverse Device Events  
529 
A serious adverse event is any untoward occurrence that:  
530 
• Results in death.  
531 
• Is life-threatening (a non-life-threatening event which, had it been more severe, might have 
532 
become life-threatening, is not necessarily considered a serious adverse event).  
533 
• Requires inpatient hospitalization or prolongation of existing hospitalization.  
534 
• Results in persistent or significant disability/incapacity or substantial disruption of the ability 
535 
to conduct normal life functions (sight threatening).  
536 
• Is a congenital anomaly or birth defect.  
537 
• Is considered a significant medical event by the investigator based on medical judgment 
538 
(e.g., may jeopardize the participant or may require medical/surgical intervention to prevent 
539 
one of the outcomes listed above).  
540 
 
541 
An Unanticipated Adverse Device Event is defined as an adverse event caused by, or associated with, 
542 
a device, if that effect or problem was not previously identified in nature, severity, or degree of 
543 
incidence.  
544 
 
545 
Serious or unexpected device-related adverse events must be reported to the IRB within 24 hours.  
546 

 
15 
Version 1.1 
Other reportable adverse events and device malfunctions (with or without an adverse event) will be 
547 
reported within 3 days of the investigator becoming aware of the event to the IRB. 
548 
Device complaints not associated with device malfunction or an adverse event must be reported 
549 
within 7 days of the investigator becoming aware of the event. 
550 
5.3 Risks and Discomforts  
551 
5.3.1 Risk of Hypoglycemia and Hyperglycemia 
552 
As a patient with diabetes, there is always a risk of having a low blood sugar (hypoglycemia) or high 
553 
blood sugar (hyperglycemia).  Symptoms of low blood sugar can include sweating, weakness, 
554 
shaking, and not feeling well.  Symptoms of high blood sugar may include increased thirst, tiredness, 
555 
blurred vision, and irritability. Instructions will be given to you to make diabetes management 
556 
decisions based on the study BGM or CGM.   You should check your blood glucose with the study 
557 
provided meter whenever you question the symptoms or expectations do not match the CGM reading.   
558 
5.3.2 CGM Sensor Placement 
559 
The CGM sensor may cause pain when it is inserted into the skin, similar to a pump site insertion or 
560 
insulin injection.  Rarely, a skin infection can happen at the site of insertion of the sensor.  Itchiness, 
561 
redness, bleeding, and bruising at the insertion site may occur.  An allergy to the tape that holds the 
562 
sensor to the skin is possible.  The risk of skin problems could be greater if you use a sensor for 
563 
longer than it is supposed to be used. There is a chance that the sensor or needle may break under 
564 
your skin.  This is not expected to occur; but, if it does, you should ask your study doctor what to do.   
565 
5.3.3 CGM Sensor Inaccuracy  
566 
There is a small risk of using CGM for insulin dosing, without a confirmatory BGM measurement, 
567 
due to the accuracy of the sensor and the possibility of an adverse event if the CGM glucose value 
568 
substantially deviates from the true glucose level, particularly when an insulin bolus is given. This 
569 
risk has been mitigated by advising participants to check the blood glucose when symptoms or 
570 
expectations do not match the CGM reading. The G5 and G6 are FDA approved with this 
571 
recommendation in the label. 
572 
5.3.4 Skin Reactions  
573 
There is a low risk for developing a local skin infection at the site of the sensor needle placement. 
574 
Itchiness, redness, bleeding, and bruising at the insertion site may occur as well as local tape 
575 
allergies.  
576 
 
577 
During each follow-up visit, each site where a CGM sensor has been worn will be assessed by study 
578 
personnel. Both acute and non-acute changes will be assessed. If a skin reaction is classified as 
579 
severe (the observation is extremely noticeable and bothersome to participant and may indicate 
580 
infection or risk of infection or potentially life-threatening allergic reaction) an Adverse Event Form 
581 
will be completed.  
582 
5.3.5 Fingerstick HbA1c and Blood Glucose Measurements  
583 
Fingersticks may produce pain and/or ecchymosis at the site. 
584 
5.3.6 Psychosocial Questionnaires  
585 
As part of the study, participants will complete psychosocial questionnaires, which include 
586 
questions about their private attitudes, feelings and behavior related to diabetes. It is possible that 
587 
some people may find these questionnaires to be mildly upsetting. Similar questionnaires have been 
588 
used in previous research and these types of reactions have been uncommon.  
589 

 
16 
Version 1.1 
5.3.7. Tele-Monitor 
590 
The main intervention in this study—daily monitoring of CGM data—could cause some patients 
591 
more anxiety because someone is “judging them” daily.  If someone objects to this approach they 
592 
will not be recruited into the study; if someone decides they don’t like the intensity of observation 
593 
they can opt out of the Tele-Monitor.  It is possible that daily interventions could worsen, rather 
594 
than improve, glycemic control by insulin dose adjustments that are too frequent.  In order to 
595 
mitigate this risk, all insulin dose adjustments will be made be the PI who is experienced in T1D 
596 
management and the frequency of adjustments will be reduced as clinically indicated. 
597 
5.3.8 Loss of Privacy 
598 
The study will collect data downloaded from study provided CGMs. The researchers will have 
599 
detailed information about daily diabetes habits. Some people may be uncomfortable with this. 
600 
Tidepool, Inc. will have access to CGM data but it will not be identified under the participant’s name. 
601 
To reduce risk of privacy loss, the Tidepool account will be set up using a study ID number instead of 
602 
subject names and a study email address.  Many of the participants in this study will already have a 
603 
Tidepool account as part of their clinical care.  The research accounts will be kept separately. 
604 
 
605 
The study may include other risks that are unknown at this time. 
606 
 
607 
 
608 
6.0 MISCELLANEOUS CONSIDERATIONS 
609 
6.1 Benefits  
610 
It is expected that the Tele-monitor will provide patients with an increased level of security, 
611 
especially at night and that frequent contacts will help improve their glucose control. 
612 
 
613 
It is possible that participants will not directly benefit from being a part of this study. However, it is 
614 
also possible that the blood glucose information from the monitor along with the information and 
615 
instructions provided for management decisions will be useful for participants’ diabetes self-
616 
management.  
617 
6.2 Participant Reimbursement  
618 
The study will provide the BG and CGM and related supplies, for the study.  
619 
 
620 
Participants who complete the study will be able to keep the study CGM devices, assuming that the 
621 
devices are functioning at the end of the study. Sensors for the CGM to be used after the study will 
622 
be the participant’s responsibility.  
623 
6.3 Participant Withdrawal  
624 
Participation in the study is voluntary, and a participant may withdraw at any time.  
625 
6.4 Confidentiality  
626 
For security purposes, participants will be assigned an identifier that will be used instead of their 
627 
name. Protected health information gathered for this study will not be shared. All of the Tidepool 
628 
data will be streaming into to a computer that is secured and password protected.  An email 
629 
address and date of birth will be created for creating an account in Tidepool, which sends the CGM 
630 
data to Tidepool. This information will be accessible to Tidepool.  All files will include only the 
631 
participant’s identifier; no names or personal information will be included.   
632 

 
17 
Version 1.1 
CHAPTER 7: STATISTICAL CONSIDERATIONS 
633 
7.1 Sample Size 
634 
10 subjects will be recruited to participate.  This number was chosen based on the usual sample size 
635 
done in pilot studies such as these, which range (in the literature) from 8 – 12 subjects.  This study is 
636 
primarily a proof of concept to show that the Tele-monitor program works effectively. 
637 
7.2 Statistical Analyses 
638 
The main goal of this project is to determine study feasibility of the intervention thus statistical 
639 
considerations were not used. 
 
640 

 
18 
Version 1.1 
CHAPTER 8: REFERENCES 
641 
 
642 
1. Graham C, Waldo D. Type 1 Diabetes in Medicare: Use of Services & Program Expenditures in 
643 
2010.Diabetes. 2013; 64:A332.  
644 
2. Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, et al. Changes in diabetes-related 
645 
complications in the United States, 1990-2010. N Engl J Med. 2014; 370:1514-23.  
646 
3. Ioacara S, Lichiardopol R, Ionescu-Tirgoviste C, Cheta D, Sabau S, Guja C, et al. Improvements in life 
647 
expectancy in type 1 diabetes patients in the last six decades. Diabetes Res Clin Pract. 2009; 86:146-51.  
648 
4. Lawrence JM, Imperatore G, Dabelea D, Mayer-Davis EJ, Linder B, Saydah S, et al. Trends in Incidence 
649 
of Type 1 Diabetes Among non-Hispanic White Youth in the United States, 2002-2009. Diabetes. 2014.  
650 
5. Geller AI, Shehab N, Lovegrove MC, Kegler SR, Weidenbach KN, Ryan GJ, et al. National estimates of 
651 
insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. 
652 
JAMA Intern Med. 2014; 174:678-86.  
653 
6. Lipska KJ, Ross JS, Wang Y, Inzucchi SE, Minges K, Karter AJ, et al. National trends in US hospital 
654 
admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA 
655 
Intern Med. 2014; 174:1116-24.  
656 
7. Stahn A, Pistrosch F, Ganz X, Teige M, Koehler C, Bornstein S, et al. Relationship between 
657 
hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular 
658 
diseases: silent hypoglycemias and silent arrhythmias. Diabetes Care. 2014; 37:516-20.  
659 
8. Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, et al. Frequency and predictors 
660 
1215 of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study. Diabet 
661 
Med. 2005; 22:749-55.  
662 
9. American Diabetes Association. 6. Glycemic Targets. Diabetes Care. 2015; 38:S33-S40.  
663 
10. Chiang JL, Kirkman MS, Laffel LM, Peters AL. Type 1 Diabetes Through the Life Span: A Position 
664 
Statement of the American Diabetes Association. Diabetes Care. 2014; 37:2034-54.  
665 
11. Weinstock RS, Xing D, Maahs DM, Michels A, Rickels MR, Peters AL, et al. Severe hypoglycemia and 
666 
diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin 
667 
Endocrinol Metab. 2013; 98:3411-9.  
668 
12. Weinstock RS, DuBose SN, Bergenstal RM, Chaytor NS, Peterson C, Olson BA, et al. Risk Factors 
669 
Associated With Severe Hypoglycemia in Older Adults With Type 1 Diabetes. Diabetes Care. 2015. 
670 
13. Pedersen-Bjergaard U, Pramming S, Heller SR, Wallace TM, Rasmussen AK, Jorgensen HV, et al. 
671 
Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and 
672 
selection. Diabetes Metab Res Rev. 2004; 20:479-86.  
673 
14. Martyn-Nemeth P, Schwarz Farabi S, Mihailescu D, Nemeth J, Quinn L. Fear of hypoglycemia in 
674 
adults with type 1 diabetes: impact of therapeutic advances and strategies for prevention - a review. J 
675 
Diabetes Complications. 2016; 30:167-77. 
676 
15. Jorgensen HV, Pedersen-Bjergaard U, Rasmussen AK, Borch-Johnsen K. The impact of severe 
677 
hypoglycemia and impaired awareness of hypoglycemia on relatives of patients with type 1 diabetes. 
678 
Diabetes Care. 2003; 26:1106-9.  
679 
16. Sturt J, Dennick K, Due-Christensen M, McCarthy K. The detection and management of diabetes 
680 
distress in people with type 1 diabetes. Curr Diab Rep. 2015; 15:101.  
681 
17. Chaytor NS, Riddlesworth TD, Bzdick S, Odegard PS, Gray SL, Lock JP, et al. The relationship 
682 
between neuropsychological assessment, numeracy, and functional status in older adults with type 1 
683 
diabetes. Neuropsychol Rehabil. 2015:1-15.  
684 
18. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and 
685 
Complications Study Research G. Long-Term Effect of Diabetes and Its Treatment on Cognitive 
686 
Function. N Engl J Med. 2007; 356:1842-52. 
687