Transition of T1DM Patients Aged Over 65 Years Into AHCL (780G) Insulin Pump: the Impact on Glucose Patterns, Quality of Life Physical & Cognitive Measures, as Well as Vascular Status
Phase: NA
Conditions: Diabetes Type 1
Sponsor: Jagiellonian University

 
 
 
Study Protocol 
 
 
 
 
Full Title 
“Transition of T1DM patients aged over 65 years  into 
AHCL (780G) insulin pump: the impact on glucose 
patterns, quality of life physical & cognitive measures, as 
well as vascular status” 
Short Title 
AHCL insulin pump in older patients 
Protocol No 
1.0 
version 
3.0 
Release date 
08 June 2022 
Type of study 
A two-centers, randomized controlled, parallel group study. 
Clinicaltrials.gov # 
Will be filled after registration of the study 
Sponsor name and address: 
Prof. Tomasz Klupa 
Trial Coordinating 
Investigator  name 
Prof. Tomasz Klupa 
Trial Coordinating 
Investigator contact details 
Prof. Tomasz Klupa 
Jagiellonian University Medical College, 
Jakubowskiego 2 
30-688 Kraków, Poland 
Tomasz.klupa@uj.edu.pl 
48 697 40 30 40 
 
Participating sites and 
investigators 
Jagiellonian University Medical College, Poland 
Device under investigation 
MiniMed™ 780G Advanced Hybrid Closed Loop (AHCL))  
 
 
 

TABLE OF CONTENT 
 
1. 
BACKGROUND OF THE STUDY ..........................................................................................................3 
2. 
TRIAL DESIGN ....................................................................................................................................4 
3. 
EVENT DEFINITIONS AND REPORTING REQUIREMENTS DURING THE STUDY .............................. 13 
4. 
AVOIDANCE OF BIAS ...................................................................................................................... 14 
5. 
DATA TO BE COLLECTED .............................................................. Błąd! Nie zdefiniowano zakładki. 
6. 
INFORMATION ABOUT QOL QUESTIONNAIRE .............................................................................. 14 
7. 
DATA HANDLING AND RECORD KEEPING ...................................................................................... 14 
8. 
STATISTICS CONSIDERATIONS: SAMPLE SIZE CALCULATION AND STATISTICAL ANALYSIS ........... 15 
9. 
INFORMATION ABOUT MONITORING AND INSURANCE ............................................................... 15 
10. ETHICAL CONSIDERATIONS, REGULATORY APPROVAL PROCESS INFORMATION, REGISTRATION 
ON CLINICALTRIALS.GOV ....................................................................................................................... 15 
11. REPORTING OF ADVERSE EVENT ................................................................................................... 16 
12. PRACTICAL VALUE AND FURTHER RESEARCH ............................................................................... 16 
13. PUBLICATION PLANS...................................................................................................................... 17 
14. REFERENCES .................................................................................................................................. 17 
 
 

 BACKGROUND OF THE STUDY 
Recent advances in insulin pumps, continuous glucose monitoring (CGM) devices, and control 
algorithms have resulted in an acceleration of progress in the development of the automated systems of 
insulin delivery including advanced hybrid closed loop (HCL) insulin pumps. The results of the AHCL 
insulin pump based studies published so far are very encouraging, including that Medtronic-sponsored 
study performed at our center “Transition of CSII/CGM naïve patients directly into AHCL (780G) 
insulin pump: the impact on glucose patterns and quality of life measures” (1-6). Unfortunately there is 
little data concerning the usage of AHCL systems in older patients.  The management of these 
individuals is particularly challenging as older adults with type 1 diabetes are especially vulnerable to 
hypoglycaemia. The recent ADA/EASD consensus underlines that the use of advanced technologies in 
older individuals is useful and should not be discontinued or a priori excluded because of the older age 
(7). Since the AHCL systems are very effective in hypoglycemia prevention they could be considered 
the treatment of choice in older patients with T1DM. The open question is how effectively would older 
individuals adopt this advanced technology, how would they accept it, and if the simplicity in terms of 
everyday usage of AHCL versus less advanced technologies would be appreciated by older individuals 
with T1DM.   Older people with diabetes have a higher risk for cognitive impairment and for physical 
disability whether this may be effected by an improvement in glucose indices is unknown.  Thus, the 
aim of this study is to assess the efficacy of AHCL in people with type 1 diabetes in improving  glucose 
indices, quality of life and physical capacity  indices. 
 
 
 
 
 

 TRIAL DESIGN 
 
2.1. Objectives  
 
The primary objective of this study is to evaluate whether the AHCL (MiniMed 780G®) system 
improves glycemic control and quality of life in older (above 65 years of age) individuals with  
withT1D and if one year ACHL treatment may affect vascular improve of those patients.  
 
 
2.2. Study design 
 
The trial is a two-centers, randomized controlled, parallel group study. Patients will be followed up 
during approximatively 12 months, with preliminary evaluation concerning efficacy and safety 
performed at 6 months.  
 
 

Figure 1: Study Design 
 
 
 
 
 
 
 
Screening visit
Run-in phase (12 days), 
blinded CGM
evaluation, QoL, 
Vascular status
Randomization visit 
MDI/CSII W/WO 
CGM
Visit 1 (day 0)
Visit 2 (day 14)
Visit 3 (day 28 
- month 1) 
Visit 4 (month 3)
Visit 5 (month 6)
Visit 6 (month 9) phone 
call
Visit 7 (month 12 
minus 14 days) 
sensor change 
Visit 8 (month 12) 
Finish of blinded 
CGM, QoL, HbA1c, 
Vascular status
AHCL group
Visit 1 (day 0) 
780G system pre-reading
CGM training & initiation
Visit 2 (day 1) 
780G System Training &
Initiation in Manual Mode
Visit 3 (day 4) 
Training re-evaluation, 
Initiation of AHCL control
Visit 4 (day 7) 
phone call: Auto Mode 
initiation follow-up
Visit 5 (day 14)
Visit 6 (day 28, month 1)
Visit 7 (month 3)
Visit 8 (month 6) 
Visit 9 (month 9) 
Visit 10 (month 12)
QoL, HbA1c, vascular status 

 
 
2.3. Visits and Procedures 
2.3.1. Run-in Phase 
 
Screening visit:  
 
Patients’ eligibility assessment,  
 
obtaining of informed consent,  
 
QoL questionnaire, the WHO-5 questionnaire as well as the General Heath question will be 
used 
 
lab tests: HbA1c, eGFR, ASPAT, TSH 
 
Vascular status : Intima-media thickness-IMT, Flow-Mediated Dilatation -FMD and Laser 
Doppler Flowmetry- LDF. 
 
Sarcopenia/functional status/frailty  will be assessed using several tools: 
1) Well validated tests of balance, strength & aerobic capacity.  This will include: 
Gait, Balance & Aerobic Capacity Measurement 
The following instrument will be used to assess gait speed balance and aerobic capacity  
Timed up and Go1 2-4   
The objective of this test is to measure the ability of a person to: stand up, walk, turn around 
and sit down safely in a timely manner. The test examines most mobility skills. The 
participant is told to get up from a chair with handles, walks 3 meters, turns, walks back, and 
sit down again.  The score is according to the length of time in seconds to complete the 
task.   The score is categorized according to the risk for falls and independent walking. The 
following cut-offs are conventionally used:  less than14 seconds = independent mobility; 15-
20 seconds= semi-independent mobility may have a some what increased risk for falls & 
needs further evaluation some may need a walking aid; 20-30 seconds= dependent mobility: 
need help walking, 50% with a cane, 40% walker, 10% supervision. Some will need help in 
transfers, and most will require help using the toilet. Many in this category won’t go outside 
the home alone.  Data suggests that the timed "Up & Go" test is a reliable and valid test for 
quantifying functional mobility that may also be useful in following clinical change over time.  
6 min walk1,5-7The six-minute walk test (6MWT) measures the distance an individual is able to 
walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk 
as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as 
they traverse back and forth along a marked walkway.  The six minute walk distance in 
healthy adults has been reported to range from 400m to 700m. People with lower vs. higher 
scores on the 6 minute walk are at higher risk for falls, disability, frailty, hospitalization and 
death.  
10 meter walk8: The test examines the pace and number of steps it takes a person to pass 10 
meters. A route of 10 meters is marked by two lines and a chair is placed two meters past the 
runway end line.  The subject starts the test two meters before the runway and goes 14 
meters (two meters for acceleration at the beginning and two meters for deceleration at the 
end). The score achieved is determined by the time lapsed by the participant during walking 
along the middle 10 meters.  Subject performs the test four times, the first two times are for 
practice: measurement occurs only during the third and fourths time.  In addition to 
measuring the speed, the number of steps required to cross the short distance are also 

counted.  Studies have a shown that better gait speed is associated with a lower risk for 
functional decline, hospitalization and mortality.9,10 
Berg Balance Scale (BBS):  The berg balance test includes 14 tasks which evaluate static and 
dynamic balance. Each task receives a score of 0 to 4 points - depending on the quality and 
task execution time.40-42 The maximum score is 56 points. The scores are dichotomized in the 
following manner:  
1. Scores below 36 indicate impairment with an increased risk for falls. 
2. Scores between 37-45 indicate need for a walking aid in order to walk in a safe manner. 
3. Scores above 45 indicate an independent walker without an increased risk of falls.  
The equipment used for the Berg balance test is a step stool, a mat table, a chair with arms, a 
tape measure, a stopwatch, a pen, and a table.  Studies have shown that individuals with 
scores indicating impaired balance are at increased risk of falls resulting in hospitalizations 
and deaths.11  
 Four Square Step Test (FSST) 12 
The test evaluates dynamic balance in a high functional level and features walk forward 
backwards left and right above 2 90 cm and 2.5 cm high long sticks that divid the floor into 
four squares. The participant is stands in square 1 facing no. 2 square. The goal is to walk as 
quickly as possible in all the squares in the following order: from 1 to- 2,3,4,1,4,3,2 and 1 
without touching the sticks. The score is the time required to complete the entire route.   
 
Grip Strength 
The maximum grip strength is examined utilizing the Jammer dynamometer.  The test is 
conducted in a neutral hand position and repeated three times. The score is the average 
strength in kg this is compared to the general population according to age and gender.43-46 
30 second chair stand.   
The purpose of this test is to assess lower body strength.  The participant is required to rise 
from sitting position with arms crossed as many times as possible in 30 seconds. Scoring is 
according to the number of stand executed in 30 seconds.47  
 
Fried Scale 
Frailty is defined as the presence of at list three components.34  
i. Weight loss: “In the last year have you lost more than 10 pounds unintentionally (not 
due to dieting or exercise)?  
ii. Poor endurance and energy: as indicated by self-report of exhaustion. Self-report 
exhaustion, identified by two questions from the CES-D scale. 
iii. Low Physical Activity level: kilocalories expended per week, calculated adjusted 
according to age and gender. 
iv. Walk time: over seven seconds to pass three meters 
 
 
2) Participants will be asked to install an app developed in-house for the assessment of clinical 
sarcopenia in older people with diabetes (EFSD grant).   
 
Cognitive function will be assessed at baseline using the Montreal  Cognitive Assessment 
(MOCA)13 and a digital version of the Digital Symbol Substitution Test (DSST)14 

 
 
. 
 
Run-in phase:  
 
Patient continues MDI/CSII treatment as per routine procedures 
 
The patient will be instructed to perform ≥ 4 blood glucose (BG) measurements per day 
 
Blinded CGM evaluation is performed for 12 days.  
 
Randomization visit:  
 
BG meter data download, data review and optimization of MDI/CSII management.  
 
Blinded CGM data download.  
 
Patients will be randomized to either: 
o MiniMed 780G AHCL system, also referred to AHCL group 
o MDI/CSII 
 
Randomization will be done by Random Allocation Software to allow fair distribution among sites and 
eliminate place for bias. http://random-allocation-software.software.informer.com/2.0/ 
 
2.3.2. Study phase 
 
Both groups will have a similar number of visits in order to minimize bias. However, the AHCL group 
will have 2 additional visits to allow for patients to be trained on the AHCL system.  
 
 
MDI/CSII group:  
The patient continues MDI/CSII treatment as per routine procedures  
 
Visit 1 (day 0, can be combined with the randomization visit): BG meter data download, data 
review and optimization of MDI management.  
 
Visit 2 (Visit 1 + 14 days, window +/- 3 days): BG meter data download, data review and 
optimization of MDI management 
 
Visit 3 (Visit 2 + 14 days, window +/- 3 days – month 1): BG meter data download, data review 
and optimization of MDI/CSII management 
 
Visit 4 (month 3): BG meter data download, data review and optimization of MDI/CSII 
management 
 
Visit 5 (month 6): BG meter data download, data review and optimization of MDI/CSII 
management, blinded CGM evaluation start. Preliminary evaluation  
 
Visit 6 (month 9) – phone call 
 
Visit 7 (month 12 minus 14 days) - phone call: blinded CGM - sensor change.  
 
 Visit 8 (Visit 6 + 6 days, window +/- 1 day): QoL questionnaire, blood sample for HbA1c lab 
test, blinded CGM data download, . vascular status : Intima-media thickness-IMT, Flow-
Mediated Dilatation -FMD and Laser Doppler Flowmetry- LDF. 
 
  
 
Study conclusion. 

 
 
 
AHCL group:  
 
Visit 1 (day 0, can be combined with the randomization visit): the patient will get the pre-
reading materials on the 780G system, to be read before Visit 2. CGM training and initiation. 
 
Visit 2 (Visit 1 + 1 day, window +7 days): 780G system training and initiation in Manual Mode.  
 
Visit 3 (Visit 2 +3 days, window +3 days): 780G system data download. Auto Mode readiness 
assessment. 780G system initiation in Auto Mode with AHCL control 
 
Visit 4 (Visit 3 + 3 days, window +1 day) – phone call: Auto Mode initiation follow-up. 
 
Visit 5 (Visit 4 + 7 days, window +/- 3 days): 780G system data download, therapy assessment 
and optimization 
 
Visit 6 (Visit 5 + 14 days, window +/- 3 days, month 1): 780G system data download, therapy 
assessment and optimization 
 
Visit 7 (month 3): 780G system data download, therapy assessment and optimization 
 
Visit 8 (month 6): 780G system data download, therapy assessment and optimization. 
Preliminary evaluation of efficacy and safety (see primary and secondary endpoints except 
for vascular status assessment) 
 
Visit 9 (month 9):  
 
Visit 10 (month 12): 780G system data download, QoL questionnaire, blood sample for HbA1c 
lab test, vascular status : Intima-media thickness-IMT, Flow-Mediated Dilatation -FMD and 
Laser Doppler Flowmetry- LDF. 
 
  
 
 
Study Conclusion 
 
 
2.4. Inclusion criteria  
 
1. Age over 65 years 
2. T1DM 
3. Willing to participate in a study for the specified duration 
4. Willing to perform ≥ 4 finger stick blood glucose measurements daily 
 
5. Willing to wear the system continuously throughout the study 
6. Glycosylated hemoglobin (A1C) value less than 10.0% at time of screening visit 
7. Treated with MDI/CSII (with exclusion of 780G) 
8. Willing to perform at least 4 BGM/day, when on MDI/CSII 
9. Lack of advanced complications of diabetes, eGFR>30 
 
2.5. Exclusion criteria 
1. Severe concurrent illness 
2. Laboratory abnormalities, or medications that might affect study participation,  
3. Severe renal impairment (eGFR<30) 

4. hemoglobin A1c value above 10% 
5. previous treatment with  780G 
 
2.6. Study endpoints  
 
Primary endpoint:  
 
Between group difference in the percentage of time spent within range with sensor glucose (SG) 
between 70–180 mg/dL (TIR) (3.9-10.0 mmol/L). 
 
Secondary endpoints: 
 
Between groups difference in the percentage of participants achieving TIR >70% 
 
Between group difference in the percentage of time spent: 
o in hyperglycemic range with SG > 250 mg/dL (13.9 mmol/L) 
o in hyperglycemic range with SG > 180 mg/dL (10.0 mmol/L) 
o in hypoglycemic range with SG < 54 mg/dL (3.0 mmol/L) 
o in hypoglycemic range with SG < 70 mg/dL (3.9 mmol/L) 
The above 4 endpoints will be also categorized by daytime (06:01 to 23:59) and night-time (00:00 to 
06:00). 
 
Between group difference in the mean glucose level 
 
Between group difference in the glycemic variability measure by SD and CV 
 
Between group difference in the HbA1c levels 
 
Between group difference in the Diabetes Quality of Life (QoL) questionnaire score. 
 
 
 
Differences in baseline vs end of the study in vascular status as measured with IMT, FMD, LDF 
 
Difference in physical capacity indices listed in screening visit   
 
Safety endpoints:  
 
Number of severe hypoglycemic episodes  
 
Number of DKA events 
 
Number of hospitalisations 
 
2.7. Devices usage in the study 
2.7.1. Run-in Phase 
The Guardian™ Link 3 transmitter and Guardian™ Sensor 3 will be used in a blinded manner to collect 
CGM data for 2 weeks at baseline in all participants.The Guardian™ Link 3 transmitter will not be linked 
to a MiniMed™ pump, and therefore the sensor data will  not be visible to the subject. 
The data will be downloaded from the transmitter in the hospital to a computer by study team 
members, using a transmitter dock (Dock) and a specific software (Download Utility software). This 
data will not be used for therapy adjustment during the study. It will only be used for study data 
analysis. 
 
 

2.7.2. MDI/CSII Group 
Blinded CGM will be used at study end for 2 weeks to collect CGM data in the MDI/CSII group. The 
process will be the same as described for the run-in phase.  
 
 
 
2.7.3. AHCL Group 
 
 
In addition, patients from the AHCL group will use the MiniMed 780G AHCL system with 
Guardian™ Sensor 4.  
The AHCL system will be initiated first in Manual Mode (i.e. without AHCL control) with suspend before 
low feature (Visit 1).  
The validated protocol for SAP initiation, as previously described (8). In short, the protocol inputs the 
current insulin program (MDI) and calculates a 10–20% reduction in total daily dose, with a 40/60 
basal/bolus distribution in four or five basal rates. Insulin-to-carbohydrate ratio (ICR) settings utilize 
the formula of 300–450/total daily dose (TDD) and the formula of 90–110/TDD (mmol/L) with two CF 
settings; the nighttime CF factor is set 10–20% higher than the daytime CF. Active insulin is set time 
(3 h); suspend before low feature is turned on with a threshold of 3.0–3.8 mmol/L (55–70 mg/dL), and 
glucose target ranges from 5.0 to 7.2 mmol/L (90–130 mg/dL. 
 
The AHCL system will be initiated in Auto Mode (i.e. with AHCL control) at Visit 2 with the settings in 
the below table. The Insulin to Carb ratio (ICR) and the Active Insulin Time (AIT) may be adjusted by 
the physician during the study. The glucose target may not be adjusted, unless in case of safety 
concerns. The patients may not adjust system settings without consulting with the physician. 
 
Basal insulin target of 
sensor glucose:  
100 mg/dl 
Insulin-Carb-Ratio:  
Defined by the rule 500/TDD. 
TDD is the one observed during the 
period in Manual Mode 
Active Insulin Time: 
2.5 hours 
 
At each visit, the AHCL system data will be downloaded and reviewed by the physician. The patient 
interaction with the system will be evaluated, included sensor calibration, bolus management (before 
the meals and for corrections as needed), alarms and Auto Mode exits. 
At each visit, the glycemic control will be reviewed, and system settings re-assessed and adjusted as 
needed, including ICR, AIT and basal rates in Manual Mode. 
 
 
2.8. Training process organization 
 
2.8.1. Study staff training 
Training of the Investigational Centers staff on the conduct of the study and the devices being used in 
the study will be performed before the protocol is implemented.  All participating physicians, nurses 
and coordinators will be trained on the 780G system and the professional CGM. Specific Investigational 

Center staff will be trained on each of the system’s components. Training will contain both lecture and 
hands-on experience. 
2.8.2. Patient training 
At screening, all participants will be met by diabetes educator and dietician to verify their knowledge 
related to intensive, functional insulin therapy. Patients not meeting the requirements will not be 
eligible to pursue the study.  
The patients randomized to the AHCL group will be trained both in the field of technical aspect of the 
usage of this technology and clinical aspects of the 780G based diabetes management. The successful 
training will be confirmed with 780G system Training Checklist developed by investigator.  
This training will include basics on insulin pump therapy, such as basal/bolus concepts, blood glucose 
target ranges, and insulin sensitivity; and basics on pump features, including how to program the 
pump, how to use the Bolus Wizard calculator, the importance of using the Bolus Wizard for all meals 
and correction doses, and the use of infusion sets and reservoir management. The training will also 
cover all the topics related to CGM usage. 
A special attention will be accorded to the specific topics related to AHCL algorithm functioning, with 
“Let the algorithm work” treatment attitude.  
 

 EVENT DEFINITIONS AND REPORTING REQUIREMENTS DURING THE STUDY 
Definitions: 
Adverse Event (AE) (ISO14155-2) Any untoward medical occurrence in a subject An AE can, therefore, 
be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal (investigational) product or medical device, 
whether or not related to the medicinal (investigational) product or medical device. 
Serious Adverse Event (SAE) (ISO 14155-2) An adverse event that  (a) Led to a death (b) Led to a serious 
deterioration in the health of the subject that • resulted in life threatening illness or injury, • resulted 
in a permanent impairment of a body structure or a body function • required in-patient 
hospitalization* or prolongation of existing hospitalization • resulted in medical or surgical 
intervention to prevent permanent impairment to a body structure or a body function  (c) Led to fetal 
distress, fetal death or a congenital abnormality or birth defect  *Inpatient Hospitalization is defined 
as: 24 hour acute admission to the hospital based on urgent medical need rather than elective 
admission. Note: A planned hospitalization for pre-existing condition, or a procedure required by the 
CIP, without a serious deterioration in health, is not considered to be a serious adverse event.   
 Serious Adverse Device Effect (SADE) (ISO 14155-2) Adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made or if 
circumstances had been less opportune.  
 Unanticipated Adverse Device Effect (UADE) (21 CFR 812.3(s)) Any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects.  
 “Severe Hypoglycemia” is an event requiring assistance of another person to actively administer 
carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with 
sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be 
available during such an event, but neurological recovery attributable to the restoration of plasma 
glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose 
concentration. (American Diabetes Association Workgroup on Hypoglycemia, Diabetes Care 28:1245-
1249, 2005)  
“Severe Hyperglycemia” is defined as Hyperglycemia (blood glucose >270 mg/dL) with blood glucose 
ketones >0.6mmol/L or accompanied by symptoms of nausea, vomiting or abdominal pain.  
 “Diabetic Ketoacidosis/DKA” is defined as: Hyperglycemia (blood glucose >250 mg/dL or >13.9 
mmol/L) with either low serum bicarbonate (<15 mEq/L) and/or low pH (<7.24) Anion gap (> 12) and 
either ketonemia or ketonuria and requiring treatment within a health-care facility. (American 
Diabetes Association-Diabetes Care, Volume 27, Supplement 1, January 2004). 
The relatedness of the event to the study device or procedures will be determined for each adverse 
event. 

The following definitions should be considered when determining the relationship of the event to the 
device or study procedure: 
 
Definite – clearly related to the device or procedure  
 
Probable – likely related to the device or procedure  
 
Possible – may be related to the device or procedure  
 
Unlikely – doubtfully related to the device or procedure  
 
Not Related – clearly not related to the device or procedure  
 
Unknown – not enough information exists to determine 
Details of related adverse events, including episodes of severe hypoglycaemia, diabetic ketoacidosis, 
lipohypertrophy and injection/ infusion site infections, will be collected at each study visit and reported 
according to the requirements of the Bioethical Committee and to Medtronic. Adverse events will be 
captured by patients, carers and clinicians treating diabetes, and from interrogation of local hospital 
databases for details of hospital attendances.  
 AVOIDANCE OF BIAS 
Participants will be randomised using a secure web-based randomisation programme. Participants will 
be randomised to each treatment arm in a 1:1 ratio. The randomisation code will be generated by a 
statistician using block randomisation with the random variable block size method.  
Missing data will be monitored and strategies developed to minimise its occurrence; however, as much 
data as possible will be collected about the reasons for missing data and this will be used to inform the 
handling of missing data. 
 
 INFORMATION ABOUT QOL QUESTIONNAIRE 
The following QOL questionnaire will be used: Speight J, Woodcock AJ, Reaney MD, Amiel SA, Johnson 
P, Parrott N, Rutter MK, Senior P, Smith R, Shaw JAM. The ‘QoL-Q Diabetes’ – a novel instrument to 
assess quality of life for adults with type 1 diabetes undergoing complex interventions including 
transplantation; presented at the Diabetes UK Professional Conference (Liverpool, UK: March 2010). 
The questionnaire will be translated by study team under translation agreement along with Linguistic 
Validation Guidelines obtained from authors.  
 DATA HANDLING AND RECORD KEEPING 
The investigator will retain all records and documents pertaining to this study. Data will be stored in a 
University Hospital in Krakow Data Archive Database. The Investigator will retain the source 
documents from which the information entered on the eCRF was derived. These records are to be 
retained in a secure storage facility maintained by the Investigational Center until 2 years after 
termination of the study. The Investigator should not dispose of these records without the approval of 
the Sponsor. 

All data required for analysis will be captured on Case Report Forms (CRFs) developed by investigator. 
The Investigator will ensure that all CRFs are completed promptly, completely, and accurately. 
Information on case report forms will conform to the information in the source documents. 
 
 STATISTICS CONSIDERATIONS: SAMPLE SIZE CALCULATION AND 
STATISTICAL ANALYSIS 
 
Statistical Hypothesis 
The null-hypothesis Ho: TIRMD/CSIII = TIRAHCL will be tested against the alternative hypothesis HA: 
TIRMDI/CSII ≠ TIRAHCL, where TIRMDI/CSII and TIRAHCL are the mean Time in Range (70–180 mg/dL) in the 
MDI/CSII and the AHCL groups, respectively. 
Sample size 
Using data from the study previously performed at our center a mean TIR=80% (Std=15%) in the AHCL 
group and a mean TIR= 65% (Std=15%) in the MDI/CSII group. For a two sided two-sample t-test, a 
total sample size of 40 subjects is required to test the hypothesized difference in population means of 
15% with a 95% confidence level, 80% power and attrition rate of 15%.  
Analysis of primary endpoint 
The primary analysis will use a two-sample t-test to compare the mean TIR between the randomized 
arms of the study. The analysis will be adjust by baseline TIR. The mean TIR in the patients in the AHCL 
arm will be claimed to be smaller than then mean TIR in the MDI arm if the average TIR is smaller in 
the AHCL arm and the associated p-value of the test is less than 0.05. No extra adjustments are needed 
for this nested test. 
 
 INFORMATION ABOUT MONITORING AND INSURANCE 
All records and documents pertaining to this study will be available for inspection by the appropriate 
regulatory agencies.  
All the study participants will be insured, the insurance costs are included into the budged proposal. 
 
 ETHICAL CONSIDERATIONS, REGULATORY APPROVAL PROCESS 
INFORMATION, REGISTRATION ON CLINICALTRIALS.GOV 
The study protocol and consent form will be presented for approval to the local institutional ethics 
committee.  The study will not be started until the written approval is granted. The study will be 
conducted in line with the Good Clinical Practice provisions of the Declaration of Helsinki with all 

amendments and local regulatory requirements. Written Patient Informed Consent (PIC) will obtained 
from all participants before enrolment; 
Individuals who will participate to the study will be informed that they will not be guaranteed the use 
of the pump either during or at the end of the study. However, those pump participants who express 
a preference to continue therapy and have measurable evidence of will be supported by their diabetes 
team in seeking the options l for continuation of pump therapy. 
Participants will be free to withdraw their participation to the study at any time.  
 
 REPORTING OF ADVERSE EVENT 
The Investigator will report to sponsor ALL adverse events that occur during the subject’s participation 
in the clinical study. A pre-existing medical condition will only be documented as an adverse event if 
the condition worsens during the course of the subject’s participation in the study. To provide further 
clarification, any adverse event that is determined to be related to the study (procedure and/or 
devices, anticipated or unanticipated) will be reported to sponsor along with those adverse events not 
related to device or study procedure. Non-serious Adverse events will be reported to the sponsor 
within 14 days of subject report to the site. For serious adverse events, reporting will be required to 
sponsor within 24 hours of site awareness.   
A complete description of the event including treatment and interventions provided by medical 
professionals will be included on the AE CRF. The investigator will provide the sponsor with the 
necessary medical records to support the adverse event. Throughout the course of the study, 
Investigational Center staff will make all efforts to remain alert to possible reportable adverse events 
or untoward findings. Reports of adverse events will be requested from subjects at each visit and 
adverse event CRFs will be completed. Investigational Center staff will assess the intensity of each 
adverse event and its relationship to study procedures or devices.  
  
Adverse events that will be assessed to have a relationship to a study procedure or study device will 
be analyzed by the Medtronic to determine whether or not there is a connection to mis-use of the 
device(s) or user error.    
  
Events that are moderate and severe in intensity, all SAE, SADE and UADE that have not resolved at 
the time of the subject’s discontinuation or completion of the study will be followed until the medical 
outcome is determined or until no further change in the condition is expected.  
 
 PRACTICAL VALUE AND FURTHER RESEARCH 
We expect to see a significant improvement in both clinical outcomes and Quality of Life in  
patients who are naïve to pump and CGM technologies as they onboard on AHCL system. The 
consequence will be to broaden the population considered eligible to AHCL therapy and provide for 
the improvement of access.  

 PUBLICATION PLANS 
We shall disseminate findings to study participants and through peer reviewed publications and 
conference presentations. The conferences of choice to present outcomes of our study will be: 
 
ATTD 
 
EASD 
 
ADA 
Journals of choice where we will try to publish our study: 
 
Diabetes Care (first choice) 
 
Diabetologia (second choice) 
 
 
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