Assessment of the Impact of Real-Time Continuous Glucose Monitoring on People Presenting With Severe Hypoglycaemia
Phase: NA
Conditions: Diabetes Mellitus, Type 1, Hypoglycemia Unawareness, Hypoglycemia
Sponsor: Imperial College London

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
 
 
Assessment of the Impact of Real-time 
Continuous Glucose Monitoring on People 
Presenting with Severe Hypoglycaemia 
(AIR-CGM) 
 
 
 
 
V1.0  
 
 
 
MAIN SPONSOR: Imperial College London 
FUNDERS: Dexcom 
STUDY COORDINATION CENTRE: Imperial College London 
NRES reference:  
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
Study Management Group 
 
Chief Investigator: Professor Nick Oliver 
 
Co-investigators: Dr Monika Reddy (Imperial College London) 
 
Statistician: Ian Godsland 
 
Study Management: Narvada Jugnee 
 
Project Manager: Maria Thomas 
 
 
Clinical Queries 
 
Clinical queries should be directed to Professor Nick Oliver who will direct the query to the 
appropriate person 
 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study.  For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Gary Roper, 
 
 
Head of Regulatory Compliance, 
 
 
AHSC Joint Research Compliance Office, 
 
 
Imperial College London and Imperial College Healthcare NHS Trust, 
 
 
Room 215, 
 
 
Level 2, Medical School Building, 
 
 
Norfolk Place, 
 
 
London, W2 1PG. 
 
 
Tel: 020 7594 1872 
 
 
E-mail: gary.roper@imperial.ac.uk 
 
Funder 
Dexcom 
 
 
This protocol describes the study and provides information about procedures for entering participants.  
Every care was taken in its drafting, but corrections or amendments may be necessary. These will be 
circulated to investigators in the study.  Problems relating to this study should be referred, in the first 
instance, to the Chief Investigator.  
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for Health 
and Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data Protection 
Act and other regulatory requirements as appropriate.  
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
Table of Contents 
 
1. 
INTRODUCTION 
6 
1.1 
BACKGROUND 
6 
2.  
STUDY OBJECTIVES 
8 
3. 
STUDY DESIGN 
8 
3.1 
RECRUITMENT 
9 
4. 
PARTICIPANT ENTRY 
11 
4.1 
PRE-REGISTRATION EVALUATIONS 
11 
4.2 
INCLUSION CRITERIA 
11 
4.3 
EXCLUSION CRITERIA 
11 
4.4 
WITHDRAWAL CRITERIA 
11 
5. 
ADVERSE EVENTS 
12 
5.1 
DEFINITIONS 
12 
5.3 
REPORTING PROCEDURES 
12 
6. 
ASSESSMENT AND FOLLOW-UP 
13 
7. 
STATISTICS AND DATA ANALYSIS 
14 
8. 
REGULATORY ISSUES 
15 
8.1 
ETHICS APPROVAL 
15 
8.2 
CONSENT 
15 
8.3 
CONFIDENTIALITY 
15 
8.4 
INDEMNITY 
15 
8.5 
SPONSOR 
15 
8.6 
FUNDING 
15 
8.7 
AUDITS 
16 
9. 
STUDY MANAGEMENT 
16 
10. 
PUBLICATION POLICY 
16 
11. 
REFERENCES 
16 
11. 
APPENDICES 
17 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
GLOSSARY OF ABBREVIATIONS 
CGM 
Continuous glucose monitoring 
T1DM 
Type 1 diabetes mellitus 
PAID 
Problem Areas in Diabetes 
CGMSS 
Glucose Monitoring System Satisfaction Survey  
HFS 
Hypoglycaemia Fear Survey 
HbA1c 
Haemoglobin A1 C 
NHS 
National Health Service 
ECG 
Electrocardiogram 
SMBG 
Self-monitoring of blood glucose 
RT CGM 
Real-time continuous glucose monitoring 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KEYWORDS 
Type 1 diabetes, continuous glucose monitoring, glucose, insulin, hypoglycaemia 
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
STUDY SUMMARY 
 
TITLE Assessment of the Impact of Real-time Continuous Glucose 
Monitoring on People Presenting with Severe Hypoglycaemia 
DESIGN Randomised open-label parallel group study 
 
AIMS This study aims to assess the impact of real-time continuous glucose 
monitoring on the frequency, duration, awareness and severity of 
hypoglycaemia in people with type 1 diabetes and a recent history of 
severe hypoglycaemia, compared to usual care. 
 
OUTCOME MEASURES The primary outcome is % time spent in hypoglycaemia (<3.0mmol/L, 
55mg/dL). 
Secondary 
outcomes 
include 
other 
measures 
of 
hypoglycaemia, time in euglycaemia, overall glucose status and patient 
reported qualitative measures.  
 
POPULATION Adults with type 1 diabetes, who are CGM naïve, and having a recent 
episode of severe hypoglycaemia (<72hrs).  
ELIGIBILITY Participants with type 1 diabetes and severe hypoglycaemia requiring 
ambulance call-out or emergency department attendance within 72 
hours. 
 
DURATION 12 weeks for each participant, 52 weeks in total. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
 
Type 1 diabetes (T1DM), which affects 300,000 in the UK, is characterised by autoimmune 
destruction of the pancreatic beta cells, leading to absolute deficiency of insulin. Management 
of T1DM requires exogenous insulin administration, aiming for glucose concentrations as 
close to physiological values as possible. Intensive management of T1DM improves glucose 
control and reduces the risk of microvascular diabetes complications and cardiovascular 
disease [1]. In the UK diabetes consumes more than 10% of the National Health Service 
budget [2] and in the USA a relatively greater amount is spent on type 1 compared with type 
2 diabetes (8.6% of the diabetes budget compared with 5.6% of diabetes prevalence) [3]. 
Medication and insulin pump therapy accounts for less than 10% of diabetes expenditure with 
the majority of costs incurred in the treatment of complications [4]. 
 
Optimal control remains challenging to achieve and intensive insulin treatment increases the 
risk of severe hypoglycaemia, with lower glucose values also associated with an increased 
frequency and severity of moderate hypoglycaemia [5, 6]. Severe hypoglycaemia is defined 
as any episode of hypoglycaemia requiring the assistance of a third party actively to treat. 
Hypoglycaemia is associated with morbidity and even mortality, and places a financial burden 
on health systems. 
 
Severe hypoglycaemia costs £13million per year in NHS costs [7]. Between 4 and 10% of 
deaths in people with type 1 diabetes are attributed to hypoglycaemia and the risk of severe 
hypoglycaemia increases 6-fold in people with impaired awareness of hypoglycaemia. 
Avoidance of hypoglycaemia is associated with restoration of hypoglycaemia awareness and 
this may be enabled by the use of continuous glucose monitoring. 
 
In type 1 diabetes real-time continuous glucose monitoring (CGM) improves overall glucose 
control in all age groups when used continuously, reduces hypoglycaemia in people with an 
HbA1c <7.0%, and may reduce severe hypoglycaemia [8-10]. 
 
In England continuous glucose monitoring is supported by NICE for people with type 1 
diabetes who are willing to commit to using it at least 70% of the time and to calibrate it as 
needed, and who have any of the following despite optimised use of insulin therapy and 
conventional blood glucose monitoring [11]: 
 
• 
More than 1 episode a year of severe hypoglycaemia with no obvious preventable 
precipitating cause. 
• 
Complete loss of awareness of hypoglycaemia. 
• 
Frequent (more than 2 episodes a week) asymptomatic hypoglycaemia that is 
causing problems with daily activities. 
• 
Extreme fear of hypoglycaemia. 
• 
Hyperglycaemia (HbA1c level of 75 mmol/mol [9%] or higher) that persists despite 
testing at least 10 times a day 
 
Addressing severe hypoglycaemia, reducing the risk of further episodes and acting promptly 
to optimise hypoglycaemia awareness are critical in people at high risk.  
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
1.2 
RATIONALE FOR CURRENT STUDY 
 
This clinical study proposes to assess the impact of real-time continuous glucose monitoring 
supported remotely by a specialist healthcare team on the frequency, duration, awareness 
and severity of hypoglycaemia in people with type 1 diabetes and a recent history of severe 
hypoglycaemia. 
 
1.3 
HYPOTHESIS 
 
Real-time CGM with adjunctive healthcare professional support provided within 72 hours of 
an episode of severe hypoglycaemia has a beneficial impact on hypoglycaemia frequency, 
duration, severity and awareness in those at highest risk of significant morbidity and mortality, 
compared with self-monitoring of blood glucose with adjunctive support. 
 
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
2.  STUDY OBJECTIVES 
 
Primary outcome:  % time spent in hypoglycaemia (<3.0mmol/L, 55mg/dL) 
 
Secondary outcome: Number of episode of serious hypoglycaemia (defined as a sensor 
glucose <3.0mmol/L (55mg/dL) for >20 minutes) 
% time spent in hypoglycaemia (<3.9mmol/L, 70mg/dL) 
% time in euglycaemia (3.9-7.8mmol/L, 70-140mg/dL) 
% time spent in target (3.9-10mmol/L, 70-180mg/dL) 
% time spent in hyperglycaemia (>10mmol/L, 180mg/dL) 
Number hypoglycaemic excursions 
Severe hypoglycaemia 
MAD% 
Glucose variability 
HbA1c 
Ambulance call-out rates 
Diabetes treatment satisfaction questionnaire 
CGM usability  
PAID 
Gold score 
Fear of hypoglycaemia survey score (HFS2) 
Cost effectiveness 
 
 
3.  STUDY DESIGN 
 
Randomised controlled study comparing the impact of real-time CGM with usual care 
following severe hypoglycaemia (Figure 1).  
 
 
Figure 1. Study design 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
3.1 
RECRUITMENT 
 
Recruitment will be undertaken in collaboration with the London Ambulance Service and from 
the Accident and Emergency departments of St Marys Hospital and Charing Cross Hospital 
in London (recruitment flow chart below). Participants will be identified following an 
episode of severe hypoglycaemia and participant information sheets will be given to 
potential subjects. Following any questions, London Ambulance Services and Emergency 
Departments will seek verbal consent to share details with study investigators, and 
send details to principal investigator through a secure website (NHS.net account). 
 
 
Figure 2. Recruitment Flow Chart 
 
 
 
3.2 
FEASIBILITY 
 
London Ambulance Service call outs for hypoglycaemia in selected geographical areas of 
North West London in 2015 calendar year are as follows: 
 
 
Between 1st March 2014 and 28th February 2015, 236 people attended the emergency 
departments of Imperial College Healthcare NHS Trust with a coded diagnosis of 
hypoglycaemia. 
 
Severehypoglycaemia
999Call
Ambulanceattendance
Dischargeonsite
Welfareringback
Within2to4hours
Seekverbalconsenttoshare
detailswithstudy
investigators
withappropriateethicalapproval
Emergencydepartment
RecruitfromED
DetailssenttoPIbynhs.net
securee-mail

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
 
 
3.3  
STUDY DURATION 
 
12 weeks for each participant, 52 weeks in total. 
 
 
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
4. 
PARTICIPANT ENTRY  
 
4.1 
PRE-REGISTRATION EVALUATIONS  
 
Episode of severe hypoglycaemia  
Age >18 years 
Diagnosis of type 1 diabetes 
 
4.2 
INCLUSION CRITERIA 
 
Adults over 18 years of age 
Severe hypoglycaemia requiring ambulance call-out or emergency department attendance 
within 72 hours 
Type 1 diabetes confirmed on the basis of clinical features 
Type 1 diabetes for greater than 3 years 
 
4.3 
EXCLUSION CRITERIA 
 
Use of CGM or Abbott Freestyle Libre device within the last 6 months (except short periods of 
diagnostic blinded use under clinic supervision) 
Use of pre-mixed insulin 
Use of regular paracetamol 
No access to smartphone or computer  
Pregnant or planning pregnancy 
Breastfeeding 
Have active malignancy or under investigation for malignancy 
Severe visual impairment 
Reduced manual dexterity 
Unable to participate due to other factors, as assessed by the Chief Investigators 
 
4.4 
WITHDRAWAL CRITERIA 
 
Participants will be withdrawn if their ability to give informed consent is impaired. Participants 
will also be withdrawn, at the chief investigators discretion, if glucose control is negatively 
impacted by the use of either intervention. 
 
 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
5. 
ADVERSE EVENTS 
 
5.1 
DEFINITIONS   
 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect 
that: 
• 
Results in death 
• 
Is life-threatening – refers to an event in which the subject was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe 
• 
Requires 
hospitalisation, 
or 
prolongation 
of 
existing 
inpatients’ 
hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other 
situations.  Important AEs that are not immediately life-threatening or do not result in death or 
hospitalisation but may jeopardise the subject or may require intervention to prevent one of 
the other outcomes listed in the definition above, should also be considered serious. 
 
5.3 
REPORTING PROCEDURES 
 
All adverse events should be reported.  Depending on the nature of the event the reporting 
procedures below should be followed.  Any questions concerning adverse event reporting 
should be directed to the Chief Investigator in the first instance.   
 
5.3.1 Non serious AEs 
 
All such events, whether expected or not, should be recorded.   
 
5.3.2 Serious AEs 
 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours.  
However, hospitalisations for elective treatment of a pre-existing condition do not need 
reporting as SAEs. 
 
All SAEs should be reported to the NRES Committee xxx where in the opinion of the Chief 
Investigator, the event was: 
• 
‘related’, i.e. resulted from the administration of any of the research procedures; 
and 
• 
‘unexpected’, i.e. an event that is not listed in the protocol as an expected 
occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies.  
The Chief Investigator must also notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
Contact details for reporting SAEs 
Fax: 0207 594 2432, attention Prof Nick Oliver 
Please send SAE forms to:  
Diabetes, Endocrinology and Metabolism Medicine 
Imperial College 
Room G3, Medical School Building 
St Mary’s Campus 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 2460 (Mon to Fri 09.00 – 17.00) 
 
 
 
6. 
ASSESSMENT AND FOLLOW-UP  
 
6.1       CLINIC VISIT 1: Screening and Randomisation  
 
Following informed consent study participants will give a full medical and medication history, 
as well as undergo a physical examination and ECG. Venous blood tests will be taken and 
sent to assess HbA1c, plasma glucose, renal function, serum C-peptide, thyroid function test, 
9 am cortisol and coeliac screen (tissue transglutaminase antibody). Women of childbearing 
age will have a urine pregnancy test. If participants meet the inclusion criteria they will be 
enrolled on to the study and will complete a semi-structured participant interview and 
questionnaires (Diabetes treatment satisfaction questionnaire, CGM usability, PAID, and Fear 
of hypoglycaemia survey score (HFS2)). A Gold Score questionnaire will also be completed. 
 
Participants enrolled will be randomised to real-time continuous glucose monitoring (RT CGM) 
or self-monitoring blood glucose (SMBG) group. Randomisation will be done using 
sealedenvelope.com and stratified by insulin delivery modality. 
 
The RT CGM group will receive a Dexcom G6 transmitter and sensors, as well as a structured 
education refresher focusing on hypoglycaemia avoidance, recognition, and management. 
Participants in the SMBG group will receive the same structured education refresher focusing 
on hypoglycaemia avoidance, recognition, and management. All education will be delivered 
by the research nurse from a predefined curriculum and will be supported by independent 
written materials.  
 
Participants will be instructed to test their capillary blood glucose if symptoms of hypo- or 
hyperglycaemia occur, in case of sensor failure or if the sensor glucose is out of the desired 
range. Participants using the G6 sensor will change sensor every ten days (or sooner in the 
event of sensor failure). Low glucose alert settings will be standardised at 4.4 mmol/L 
(80mg/dL) for all participants at the start of the study and can be reduced to 4 mmol/L 
(70mg/dL) at week 2 during the telephone visit depending on participant preference. High 
glucose alerts may be personalised. 
 
The SMBG group will additionally undergo blinded CGM at weeks 1 and 2, weeks 4 to 6 and 
weeks 9 to 12 using the Dexcom G6 system. Participants in this group will be shown how to 
insert the Dexcom G6 at the first clinic visit and sensors provided so they can do this at home. 
 
 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
6.2       FOLLOW-UP: Telephone follow-up during study period 
 
Participants will be provided telephone support twice in the first week, then weekly for the next 
3 weeks, and every 2 weeks thereafter, to optimise glucose and reduce the risk of further 
hypoglycaemia.  
 
Participants in the CGM group with an iOS or Android smartphone will be able to upload and 
share data with the Research team through the “Dexcom Share app”. Participants who do not 
have a smartphone can upload their CGM data to and online platform named “Tidepool” using 
a PC or Mac desktop computer. In total, participants will use CGM for 12 weeks. 
 
Participants in the SMBG group will be asked to self-monitor a minimum of 4 times daily and 
upload data to Tidepool, an online not-for-profit platform for individuals to selectively share 
data with clinicians to optimize diabetes management. They will receive telephone support 
from the research team, based on their Tidepool data, at the same time points as the RT-CGM 
group to optimise glucose and reduce the risk of further hypoglycaemia. Blinded CGM data 
from the SMBG group will be uploaded at the end of week 2, end of week 6 and end of week 
12. 
 
 
6.3        CLINIC VISIT 2: End of study 
 
At the end of the study (i.e. at end of 12 weeks), repeat blood tests to assess HbA1c will be 
performed. Participants will be asked to complete questionnaires and a semi-structured 
interview will be conducted, similar to that at baseline. Participants will return study equipment 
and return to their standard care. 
 
 
 
 
7. 
STATISTICS AND DATA ANALYSIS 
 
Baseline data will be taken from the first 14 days of monitoring and outcomes will be calculated 
from the last 30 days of the treatment period. 
 
Power calculation: Based on findings from our 'I HART CGM trial', we would expect 
percentage time spent in hypoglycaemia (<3.0mM) to be 64% lower in the CGM group 
compared to the self-monitoring group [mean (SD): CGM group 2.1% (2.3%); self-monitoring 
group 5.8% (5.9%)]. To demonstrate that difference as significant at p<0.05 and with 80% 
power, 25 participants would be needed in each group. To allow for a 10% drop-out 55 
participants will be recruited. 
 
Analysis: Intention to treat. The primary outcome will be assessed by two-tailed unpaired t-
test. For secondary outcomes, parametric data will be compared between the two study arms 
by two-tailed unpaired t-test for continuous variables. Non-parametric data will be compared 
using a Wilcoxon Rank sum test. 
 
Sub-analysis: Other outcomes assessed will include hypoglycaemia awareness by 
participant (Gold score). Hypoglycaemia outcomes will be assessed throughout the time 
period and nocturnal only. 
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period.   
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
 
8. 
REGULATORY ISSUES 
 
8.1 
ETHICS APPROVAL 
 
The Study Coordination Centre has obtained approval from the xxx Research Ethics 
Committee (REC) and Health Research Authority (HRA). The study must also receive 
confirmation of capacity and capability from each participating NHS Trust before accepting 
participants into the study or any research activity is carried out. The study will be conducted 
in accordance with the recommendations for physicians involved in research on human 
subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
8.2 
CONSENT  
 
Consent to enter the study must be sought from each participant only after a full explanation 
has been given, an information leaflet offered and time allowed for consideration.  Signed 
participant consent should be obtained.  The right of the participant to refuse to participate 
without giving reasons must be respected.  After the participant has entered the study the 
clinician remains free to give alternative treatment to that specified in the protocol at any stage 
if he/she feels it is in the participant’s best interest, but the reasons for doing so should be 
recorded.  In these cases, the participants remain within the study for the purposes of follow-
up and data analysis.  All participants are free to withdraw at any time from the protocol 
treatment without giving reasons and without prejudicing further treatment. 
 
8.3 
CONFIDENTIALITY 
 
The Chief Investigator will preserve the confidentiality of participants taking part in the study 
and is registered under the Data Protection Act. Confidentiality of data will be preserved during 
data transmission via the use of anonymised codes. Participants will be assigned codes based 
on order of enrolment and site at which they are enrolled (AIR-HH-001 etc. for those enrolled 
at Hammersmith Hospital, AIR-CX-001 etc. for those enrolled at Charing Cross Hospital and 
AIR-SM-001 etc. for those enrolled at St Mary’s Hospital/. Identifiable personal information will 
be stored securely in a locked room at Imperial College Healthcare NHS Trust. Annonymised 
data will be held securely in swipe-card access room at Imperial College London and on 
Imperial College London computers. The latter will be encrypted with a password. Data will be 
accessible only to the Research Team and for audit. Pseudoanonymised data will be used for 
analysis. Confidentiality of data will be preserved when sending identifiable information from 
Imperial College Healthcare NHS trust and London Ambulance Service to the Imperial College 
London research team by using encrypted NHS.net email accounts. The data will be stored at 
Imperial College London for 10 years. App security is covered in Tidepool’s privacy statement 
as they are a separate data controller. The data custodian is Professor Nick Oliver. 
 
8.4 
INDEMNITY 
 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study. 
 
8.5 
SPONSOR 
 
Imperial College London will act as the main Sponsor for this study.  Delegated responsibilities 
will be assigned to the NHS trusts taking part in this study.   
 
8.6 
FUNDING 
 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
Dexcom are funding this study.  Participants will be fully reimbursed for travel expenses. 
 
8.7 
AUDITS  
 
The study may be subject to inspection and audit by Imperial College London under their remit 
as sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research 
Governance Framework for Health and Social Care (2nd edition).  
 
 
 
 
9. 
STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through the Chief Investigator, 
Prof Nick Oliver.   
 
 
10. 
PUBLICATION POLICY 
 
Data from the study will be analysed then published in peer-reviewed scientific journals and 
presented at Scientific Conferences. A lay summary of the data will be disseminated to all 
participants and a summary of results will be publically available. 
 
 
 
11. 
REFERENCES 
 
1. 
Nathan, D.M., et al., DCCT trial Intensive diabetes treatment and cardiovascular 
disease in patients with type 1 diabetes. N Engl J Med, 2005. 353(25): p. 2643-53. 
2. 
Hex, N., et al., Estimating the current and future costs of Type 1 and Type 2 
diabetes in the UK, including direct health costs and indirect societal and productivity 
costs. Diabetic Medicine, 2017. 29(7): p. 855-862. 
3. 
Dall, T.M., et al., Distinguishing the Economic Costs Associated with Type 1 and Type 
2 Diabetes. http://www.liebertpub.com/pop, 2009. 
4. 
Herman, W.H. and R.C. Eastman, The Effects of Treatment on the Direct Costs of 
Diabetes. 1998. 
5. 
Cryer, P.E., Hypoglycaemia: the limiting factor in the glycaemic management of Type 
I and Type II diabetes. Diabetologia, 2002. 45(7): p. 937-48. 
6. 
Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control 
and Complications Trial Research Group. Diabetes, 1997. 46(2): p. 271-86. 
7. 
Leese, G.P., et al., Frequency of Severe Hypoglycemia Requiring Emergency 
Treatment in Type 1 and Type 2 Diabetes. 2003. 
8. 
Pickup, J.C., S.C. Freeman, and A.J. Sutton, Glycaemic control in type 1 diabetes 
during real time continuous glucose monitoring compared with self monitoring of blood 
glucose: meta-analysis of randomised controlled trials using individual patient data. 
Bmj, 2011. 343: p. d3805. 
9. 
Beck, R.W., et al., Effect of Continuous Glucose Monitoring on Glycemic Control in 
Adults With Type 1 Diabetes Using Insulin Injections: The DIAMOND Randomized 
Clinical Trial. Jama, 2017. 317(4): p. 371-378. 
10. 
Lind, M., et al., Continuous Glucose Monitoring vs Conventional Therapy for Glycemic 
Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections: 
The GOLD Randomized Clinical Trial. Jama, 2017. 317(4): p. 379-387. 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
11. 
Type 1 diabetes in adults: diagnosis and management | Guidance and guidelines | 
NICE. 2017. 
 
 
 
 
 
 
 
 
 
11. 
APPENDICES 
 
 
• 
Summary of investigations, treatment and assessments 
• 
Dexcom G6 instructions for use 
• 
Validated questionnaires: 
▪ 
Diabetes treatment satisfaction questionnaire 
▪ 
CGM usability  
▪ 
PAID 
▪ 
Gold score 
▪ 
Fear of hypoglycaemia survey score (HFS2) 
Tidepool Privacy Statement (https://tidepool.org/legal/privacy-policy-2-0/) 

 
 
Assessment of the Impact of Real-time Continuous Glucose Monitoring on People Presenting with Severe 
Hypoglycemia (AIR-CGM) IRAS ID 240039  
Protocol v1.0 03/08/2018 
 
 
Appendix 1: Summary of investigations, treatment and assessments 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
Week 12 
(Clinic Visit 2)
History
x
Medication 
history
x
ECG
x
Physical 
examination
x
Urine pregnancy 
test
x
HbA1c
x
x
Glucose
x
Renal function
x
TFT
x
9am cortisol
x
Coeliac screen
x
C-peptide
x
Gold Score
x
x
Participant 
interview
x
x
QoL 
Questionnaires
x
x
Diabetes 
Education
x
Randomisation
x
CGM education
x
CGM insertion
x
x
x
x
x
x
x
x
x
x
x
x
Telephone 
consultation
x (twice)
x
x
x
x
x
x
CGM group - 
CGM download
x (twice)
x
x
x
x
x
x
x
SMBG Group -
Meter download
x (twice)
x
x
x
x
x
x
x
SMBG Group - 
Blinded CGM 
download 
x
x
x
Research clinic 
visit
x
x
Clinic Visit 1 
(Screening & 
Randomisation)
EndofWeek