Continuous Glucose Monitoring for Post-kidney Transplantation in Pre-existing Type 2 Diabetes
Conditions: Kidney Transplant
Sponsor: The Cleveland Clinic

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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Continuous glucose monitoring for post-kidney 
transplantation in pre-existing type 2 diabetes 
 Study Protocol 
 
 
NCT Number: Pending 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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Continuous glucose monitoring for post-kidney 
transplantation in pre-existing type 2 diabetes 
 
 
Department of Endocrinology 
Cleveland Clinic 
9500 Euclid Avenue, Desk F-20 
Cleveland, Ohio, 44195 
USA 
 
 
 
Correspondence to:  
 
Maria Cecilia Lansang, MD, MPH 
Endocrinologist 
9500 Euclid Ave, Desk F-20, Cleveland, 
Ohio, 44195 216-445-5246, 
lansanm@ccf.org 

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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1. BACKGROUND AND SIGNIFICANCE 
About 20,000 kidney transplants take place yearly in the US. Diabetes (DM) is the most common cause 
for end-stage kidney disease (ESKD) [1] and the most common clinical condition listed for kidney 
transplant (31%) [2]. Glucose levels are relatively controlled during ESKD (due to prolonged insulin 
action, reduced glycogen stores, decreased renal gluconeogenesis). Glycemic control is then disrupted in 
the early post-transplant period because these processes are reversed with the transplanted kidney, 
patients develop insulin resistance from high dose glucocorticoids and other anti-rejection medications, 
and their appetites increase [3].  
Cleveland Clinic performs around 250 kidney transplants a year, and has successfully reduced the 
patients’ length of hospital stay (LOS) post-transplant from 5 days down to 3 days by developing an 
enhanced recovery after surgery (ERAS) pathway that has a large outpatient diabetes management 
component. That is, patients no longer stay in the hospital to have their multiple daily insulin injection 
(MDII) doses adjusted. This necessitates having a reliable source of glucose readings when they are 
discharged to adjust their MDII doses and avoid hyperglycemia/hypoglycemia, and potentially reduce 
readmissions, rejection, and delayed graft function. Continuous glucose monitoring (CGM) is a method 
of measuring patients’ glucose readings every 5-10 minutes via subcutaneous insertion of a sensor, 
reducing or even eliminating the need for painful fingerpricks (fingerpricks can be done as needed if 
there is discrepancy between the CGM reading and the patients’ clinical scenario). 
2. SPECIFIC OBJECTIVES: 
 
1)  Primary objectiveobjective  
To characterize the glucometrics ( description of glucose readings in relation to target goals, as 
discussed in the Methods section ), achieved by a CGM-based insulin titrating protocol for 
glucocorticoid taper for post kidney transplant patients  
 
 
2) Secondary objective:  
To explore the relationship between CGM glucometrics and rates of readmission, rejection, and 
delayed graft function in post kidney transplant patients 
 
 
3. RESEARCH DESIGN AND METHODS 
 
3.1Primary endpoints 
1) Ambulatory glucose profile (AGP) data glucometrics such as time in range, time below range, 
time above range, and glucose variability (coefficient of variation)  
 
2) Readmission 
 
3) Rejection 
 
4) Delayed graft function 
 
3.2 Secondary endpoints 
          1)   Levels of HbA1c at 3 months and 6 months post-transplant 
          2)  Diabetes medication adjustment at each time point (SEE schedule of assessments) 

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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If YES, which of the 
following occurred 
(can be more than 
one answer) 
• 
reduction of any insulin dose 
• 
stopped the scheduled insulin 
• 
stopped the correction insulin 
• 
stopped the basal insulin  
• 
started a non-insulin medication 
If NO, which of the 
following occurred 
(can be more than 
one answer) 
• 
stayed on the same insulin doses 
• 
increased one or more insulin doses  
• 
started a non-insulin medication without decreasing the dose of 
insulin 
 
 
Categorical and continuous variables that will be collected closest to time of signed consent (last 
available recorded value for continuous variables):  
1) Age 
2) Sex 
3) Weight 
4) Height 
5) BMI 
6) HbA1c and serum glucose reading 
7) Glucometrics based on CGM AGP, and individual CGM glucose reading download (Freestyle Libre 
readings are averaged every 5 minutes) 
8) Serum creatinine 
9) eGFR 
10) Original kidney disease 
11) Length of hospital stay for kidney transplant admission 
12) Readmission (including reason) 
13) Delay of graft function (defined as needing dialysis in the first 7 days post-transplant) 
14) Rejection 
15) Diabetes mediation and dose 
16) Appetite (qualitative: poor, fair, good, great) 
17) Carbohydrate intake (dietary recall): grams of carbohydrate per meal 
18) Prednisone taper schedule (standard upon inclusion but will note if changed to rapid)  
19) Tacrolimus, other anti-rejection medication dose 

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20) Transferred to what type of provider (PCP/local endocrinologist/CCF endocrinologist) after 3 months 
21) CGM upload (Enrollment –visit 10) with Abbott Libre. CGM upload  (after visit 10) if patient has other 
CGM prescribed- percent of CGM time above range, in range, below range (TAR, TIR, TBR), or very high, 
high, in range, low, very low 
22) Freestyle Libre or other CGM use pre and post-transplant 
 
a) If not on CGM: what are the patients' reasons for not being on a CGM, or for not using 
consistently (e.g. insurance issues, durable medical equipment company delay, does not want to 
continue, no mobile app, provider not refilling/not incorporating into management) 
 
b) If utilizing Freestyle Libre CGM, allow us to look at  retrospective data OR patient to upload 
AGP from the previous visit. If patient on a different CGM, patient to upload AGP from previous visit.  
3.3 Recruitment 
A total of 20 patients that are post kidney transplant, will undergo intervention until 3 months post-
transplant. Informed consent will be obtained prior to start of study. The final visit will be at 3 months. 
Patients will be discharged to their local endocrinologist or primary care physician at this 3-month mark. 
Data will continue to be gathered for 3 more months after exit from intervention.   
Enrollment will be within the first 2 weeks of hospital discharge.  
Screening of patients will be done through the inpatient endocrinology consult list (seen in various floors 
in the main campus hospital), or the endocrine kidney transplant clinic list (patients seen at Q8). 
Endocrine providers (physicians, nurse practitioners, pharmacists) who take care of qualifying patients 
will inform patients of this study at their visits again only mentioning a research study involving CGMs 
and kidney transplant patients.  The endocrine providers will notify the study staff if the patient has 
questions or would like to learn more.  The study staff will follow-up with the patients, provide and 
thoroughly review the consent. The patients will be given time to review the consent ask questions prior 
to making a decision to participate.  The consenting process will take place in a private exam room if 
outpatient, or in the hospital room if still admitted to the hospital. The process will be documented in 
EPIC.  
 Visits are standard of care (SOC) at the Kidney Transplant Clinic or at the Endocrinology clinic and will be 
virtual or in-person or telephone encounter (see table). Visits are twice a week for the first 3 weeks post 
discharge. Following this, visits will be every two weeks until the end of the steroid taper(final steroid 
dose), usually 7.5mg daily by 56 days after transplant (see table below). This is part of SOC.  
Standard prednisone taper 
Post op day         
Prednisone dose 
2 
60 mg twice a day 
3 
50 mg twice a day 
4 
40 mg twice a day 

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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5 
30 mg twice a day 
6 
30 mg AM and 15 mg PM 
7-13 
30 mg in AM 
14-27 
20 mg in AM 
28-41 
15 mg in AM 
42-55 
10 mg in AM 
56 and beyond 
7.5 mg in AM 
 
At Enrollment, insertion of Freestyle Libre 2 (or later version) sensor will be placed on upper arm. An 
account will also be set up on Libreview.com. This is part of SOC with diabetic patients who use CGMs. 
The patient will be asked to sign up on the product’s platform (in this case for Freestyle Libre Abbott 
products, Libreview.com). We will be collecting data from the CGM ambulatory glucose profile (AGP) 
report or from phone/reader if we are unable to link to the patient’s portal for certain visits. An insulin 
dosing protocol would be set up per patient. The patients would have already been seen by the 
inpatient endocrine team during the admission for their kidney transplant and would have been 
discharged on multiple daily insulin injection (MDII). This is part of the early recovery after surgery 
(ERAS)  pathway that we have developed with the kidney transplant team.  When patient is outpatient, 
we address dosing in order of priority by reducing or increasing the corresponding insulin by 10-100%. 
The range is wide to account for some doses that might be small (e.g. 2 units of rapid-acting insulin, for 
prednisone dose reduction, and for a change in appetite). We also make allowance for changing to non-
insulin medications, as shown in the table. 
 
Acceptable percentage of time that glucose levels are at a certain range, and insulin 
adjustment 
Glucose e and percentage of time it is acceptable for 
glucose levels to be in these ranges 
Insulin adjustment by 10-100% 
(the range is wide to account for 
some doses that might be small, 
such as 2 units of rapid-acting 
insulin, for prednisone dose 
reduction, and for a change in 
appetite 
Time in very high 
range (>250mg/dL) 
5% or less 
Increasing the corresponding 
insulin if above 5% 

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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Time in high (181-
250 mg/dL) plus 
very high range 
25% or less 
Increasing the corresponding 
insulin if above 25% 
Time In Range 
 
In range (70-180 
mg/dL) 
70% or greater 
Continue to monitor but 
decrease if prednisone dose is 
decreasing 
Time Below Range 
 
Time in low range 
(54-69 mg/dL) plus 
very low range 
4% or less 
Reducing the corresponding 
insulin if above 4% with option 
to reduce even if 4% or less 
(because we want to avoid 
further hypoglycemia) 
Time in very low 
range (<54 mg/dL) 
1% or less 
Reducing the corresponding 
insulin if above 1% with option 
to reduce even if 1% or less 
(because we want to avoid 
further hypoglycemia) 
Other insulin protocols 
Serum creatinine or 
eGFR is still 
elevated 
 
Dose adjustments will be 
towards giving less insulin 
Attempt to stop mealtime insulin and substitute with medication below 
Prednisone dose is 
10mg daily or less 
CGM shows >70% time in range 
There is no contraindication to 
the medication to be started 
Keep or reduce basal insulin. Keep the correction scale insulin while initiating medication 
changes below. Order with which medication switch is to be made; proceed to the next one 
on the list if there is contraindication or plan restriction.  

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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1. GLP-1 agonist 
2. DPP-4 inhibitor 
3. Sulfonylurea 
4. Unable to use the other DM medication types yet at this early phase post-transplant 
Stop correction scale insulin. As allowed by CGM pattern, increase basal insulin if needed to 
eliminate correction scale insulin.  
Next attempt is to stop the basal insulin by increasing the dose of the GLP-1 agonist or DPP-
4 inhibitor or sulfonylurea, or addition of a sulfonylurea to the GLP-1 agonist or DPP-4 
inhibitor.  
 
 
 
 
 
 
 
 
 
 
Outline of procedures 
Events 
Enrollment 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Time points 
within 2 
weeks of 
hospital 
dis-charge 
1 week post 
discharge 
+/-3 days* 
2 weeks post 
discharge 
+/-3 days* 
3 weeks post 
discharge 
+/-3 days* 
Week 
5 
+/-3 
days* 
Week 
7 
+/-3 
days* 
Week 
9 
+/-3 
days* 
Week 12 
(3 mo) 
+/- 1 
month 
Week 18 
(4.5 
months) 
Week 24 
 (6 mo) 
+/- 1 
month 
 
In-person 
In-person or virtual 
 
Telephone encounter 
(unless patient wants an 
in-person or virtual visit) 
In-person 
preferred, 
virtual if 
needed 
Telephone 
encounter 
(unless 
patient 
wants an 
Telephon
e 
encounter 
(unless 
patient 

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in-person 
visit) 
wants an 
in-person 
visit) 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Libreview 
Account Set-
up, CGM 
insertion, 
CGM teaching 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CGM 
download 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xa2 
 
Xa2 
 
Demographics
- age, sex, 
weight, height 
(height only 
on 
enrollment), 
BMI 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Labs - serum 
crea/eGFR/se
rum glucose 
Optional for 
some visits, 
but these are 
SOC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
      X 
 
 
 
 
 
 
 
 
 
X 
 
X 
Appetite 
evaluation  
(poor, fair, 
good, great) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Carbohydrate 
intake 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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(approximate 
grams, dietary 
recall) 
Diabetes 
medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Transplant 
medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ambulatory 
glucose 
profile (AGP) 
and individual 
glucose 
reading 
downloads 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb  
Xb  
Document - 
Readmission/ 
rejection/ 
delayed graft 
function 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Note: All visits and labs are Standard of Care (SOC). Serum crea/eGFR are ordered by the kidney 
transplant team. A1c is ordered by the endocrine team.  
*Window variances measured in business days 
a For those who remain on it; fingerstick for those who do not 
b If still on CGM; survey if not on CGM 
 
3.4 Statistical Methods 
The goal of the present study is not hypothesis testing, but rather estimation.  With 20 patients, and 
assuming that the standard deviation in the time in range will be no more than 20%, and time in range 
levels will be moderately correlated over time (r = 0.5), estimated changes in time in range will be 
estimated to within ±9.4%.  Additionally, there will be at least 80% power to detect mean changes of at 
least 13.3% in time in range over time within patients. This sample size will allow us to generally 
estimate precision of the prevalence of binary events such as readmission and delay of graft function to 
within ±20% provided that the event rate is less than 30%. 

Protocol Version 2, Dated 6-24-2024 
 
 
 
 
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Patient characteristics will be summarized overall and by group using means and standard deviations for 
continuous measures and frequencies and percentages for categorical factors. MedicationMedication 
adjustment as well as binary events such as readmission, rejection and delayed graft function rates will 
be estimated at each time point and compared over time using McNemar tests or generalized mixed 
effect models. Toevaluate continuous measures such as HbA1c and AGP metrics over time, paired t-tests 
or linear mixed models will be used. In these models, time will be the main predictor.   Estimated HbA1c 
and glucometrics levels at each time with 95% confidence limits will be estimated from the model.  
Linear mixed models are valid under the assumption of missing at random. This will be evaluated 
graphically and, if necessary, sensitivity analyses will be performed to evaluate the potential effects of 
the missing data over time. If glucometric time measures are close to the extremes of the distribution 
(i.e. near 0 or 1), then an alternate approach using beta regression to estimate the levels and changes 
may be performed. Time to readmission and rejection will be estimated using Kaplan-Meier analysis. If 
interim analyses result in a change to the insulin dosing protocol, results will be presented overall, and 
then separately for the first 10 and last 10 patients.  Stratification of results may also be performed 
based on the timing of enrollment relative to the transplant.  Analysis will be performed using SAS 
software (version 9.4; Cary, NC) or R software (version 4.1; Vienna, Austria).  Given that this is a pilot 
study, we will perform all tests using a 0.05 significance level, and focus on estimation to allow for future 
research, if warranted.  
 
4. STUDY POPULATION 
 
This is a non-randomized perspective single arm study with a planned enrollment of 20 patients.   
4.1 Inclusion Criteria 
1. Sex: men and women 
2. Ethnicity: all ethnic groups 
3. Age: ≥ 18  
4. Known type 2 diabetes before kidney transplant 
5. Kidney transplant alone 
6. On multiple daily insulin injection 
7. Standard prednisone taper 
8. Smart phone – compatible with the LibreView App 
 
   4.2 Exclusion Criteria 
1. Simultaneous pancreas-kidney transplant 
2. Allergy to Freestyle Libre components including adhesive 
3. Use of vitamin C at doses 500 mg or greater 
4. Blood dyscrasias that prevent hemoglobin A1c interpretation 
5. Lack of mobile app accessibility 
6. Rapid prednisone taper 
In the uncommon scenario, if a patient is started on a standard prednisone taper and converted to a 
rapid prednisone taper. The patient would remain in the study.  
 

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4.3 Adverse Events and Data Monitoring Committee (DMC) 
 
There will not be a data monitoring committee for this pilot project. Any AE or SAE will be reported to 
the PI, Sponsor and IRB in a timely manner once they have been disclosed to study personnel.  
 
Unanticipated non-serious adverse events assessed by the PI as being either caused by, or related to, 
the study procedures, will be reported using the Adverse Event Report form.   
 
The following adverse events are anticipated as a result of the blood collection required per the study 
procedures: pain, bruising, bleeding or infection at the site where the blood was collected from the 
subject.  Fainting may also occur as a result of blood collection. Because these events are anticipated, 
they do NOT need to be reported using the Adverse Event Report form as long as they are not assessed 
as serious. If assessed as serious, then they need to be reported. 
 
There may be some risks from wearing the Continuous Glucose Monitor (CGM) 
• 
Skin irritation at the insertion site which may include redness and rash 
• 
Infection at the insertion site (redness, soreness, warm or hot skin, drainage noted) 
• 
Discomfort 
• 
The sensor may fall off accidentialy and need to be reinserted 
• 
Exposing the sensor to MRI, CT scan, diathermy (electrically induced heat or the use of high 
frequency electromagnetic current as used in physical therapy or surgery), or x-ray may cause 
damage and incorrect readings. Patients will be asked to remove the sensor for these 
procedures. 
• 
The sensor should not be submerged more than 3 feet (1 meter) or kept underwater longer than 
30 minutes at a time.  
 
Interim analysis of glucometrics: 
Even though there is no DMC, we would like to see if our insulin dosing parameters are related to severe 
hyperglycemia and severe hypoglycemia. As such, we will do interim analysis after 10 patients.  If among 
the first 10 patients, at least 4 patients report Time in Very High Range > 10% of the time, or Time in 
Very Low Range >5% of the time, then the insulin dosing protocol will be reviewed and modified. 
 
5. DATA HANDLING AND RECORD KEEPING: 
 
A file database will be created for data collection accessible only by authorized study personnel. 
Information will be entered into the database as it is collected and patients finish the study. Each patient 
will be assigned a study number consecutively as they are enrolled. Only the study number will be used 
to identify all study-related documents such as case report forms. A master list of study numbers linked 
to patient identifiers will be maintained by the study coordinator in a secured location. Study data will 
be collected and managed using REDCap (Research Electronic Data Capture); this will include patient 
identification number, medical record number, age, gender, and ethnicity. 
If a subject withdraws from the trial or is lost to follow-up, then the subject’s data which has already 
been collected will be retained by the investigator, entered into the database and used for the study 
reporting. 
6. ETHICS: 

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The study will be conducted in compliance with ICH GCP and applicable regulatory requirements, and in 
accordance with the Declaration of Helsinki. 
Voluntary signed informed consent will be obtained from each study subject prior to initiating any 
research interventions. Informed consent will be documented in the subject’s medical record. 
This study is subject to the review and approval of the Cleveland Clinic Institutional 
Review Board prior to initiating any study activities. 
 
7. PUBLICATION PLAN: 
 
Upon study completion, the data generated will be submitted in abstract form to an endocrine-,  
diabetes-, or kidney transplant-related meeting, and subsequently submitted  to a journal for 
consideration for publication. 
 
 
8. CITATIONS: 
 
Burrows NR et al. Reported Cases of End-Stage Kidney Disease — United States, 2000–2019. MMWR 
Recomm Reports. 2022;71(11):412-415 
Hart A et al. OPTN/SRTR 2019 Annual Data Report. Am J Transplant 2021;21(2):21-137 
Iqbal A, Zhou K, Kashyap SR, Lansang MC. Early Post-Renal Transplant Hyperglycemia. J Clin Endocrinol 
Metab. 2022 Jan 18;107(2):549-562