How Common is Hypoglycaemia in Older People With Diabetes Who Have Falls, Dizziness or Other Symptoms Suggestive of Hypoglycaemia? A Continuous Glucose Monitoring Study
Phase: NA
Conditions: Diabetes, Hypoglycaemia
Sponsor: University of East Anglia

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How common is hypoglycaemia in older people with diabetes who have falls, dizziness or other 
symptoms suggestive of hypoglycaemia? A continuous glucose monitoring study 
 
Version: v2 
Date: 3 September 21 
Sponsor: University of East Anglia 
 
Authorisation: Chief investigator 
Name: Katharina Mattishent 
Role: Clinical Lecturer in Older People’s Medicine  
 
Authorisation: Sponsor 
Name: Graham Horne 
Role: Project Officer (MED), Research and Innovation Services 
 

 
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Administrative information  
This document describes the single-centre, non-randomised study investigating the use of 
continuous glucose monitoring (CGM) in older people with diabetes presenting to hospital 
with falls and/or other symptoms suggestive of undetected hypoglycaemic episodes, 
sponsored by the University of East Anglia (UEA).  
It provides information about procedures for entering participants into the trial, and 
provides sufficient detail to enable: an understanding of the background, rationale, 
objectives, trial population, the medical device, methods, statistical analyses, ethical 
considerations, dissemination plans and administration of the trial; replication of key 
aspects of trial methods and conduct. 
1.1 
Compliance  
The trial will be conducted in compliance with the approved protocol, the Declaration of 
Helsinki (2008), the principles of Good Clinical Practice (GCP) as laid down by the 
Commission Directive 2005/28/EC with implementation in national legislation in the UK by 
Statutory Instrument 2004/1031 and subsequent amendments, the UK Data Protection Act, 
and the National Health Service (NHS) Research Governance Framework for Health and 
Social Care (RGF).  
1.2 
Sponsor 
UEA is the trial sponsor and has delegated responsibility for the overall management of the 
study to the Chief Investigator. Queries relating to sponsorship of this trial should be 
addressed to the Chief Investigator, or via the trial team. 
 
 

 
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1.3 Structured Trial Summary 
 
Source of Monetary or Material 
Support 
Norfolk Diabetes Trust 
Sponsor 
University of East Anglia 
Contact for Scientific Queries 
Dr Katharina Mattishent 
Norwich Medical School 
University of East Anglia 
Bob Champion Research and Education Building 
Norwich 
NR4 7TJ. 
e-mail: k.mattishent@uea.ac.uk  
Public Title 
How common is hypoglycaemia in older people with diabetes who 
fall? 
 
Scientific Title 
How common is hypoglycaemia in older people with diabetes who 
have falls, dizziness or other symptoms suggestive of hypoglycaemia? 
A continuous glucose monitoring study 
Countries of Recruitment 
England 
Health Condition(s) or Problem(s) 
Studied 
Older people with diabetes 
Intervention 
Use of continuous glucose monitoring (CGM) 
Key Inclusion and Exclusion Criteria 
Inclusion Criteria: Patients 75 years and older, Type 1 or Type 2 
diabetes mellitus on insulin and/or sulfonylureas, presenting to 
hospital with a fall and/or symptoms suggestive of unrecognised 
hypoglycaemia (such as dizziness, feeling muddled). 
 
Exclusion criteria: treatment with metformin only, lack of capacity, 
not willing to participate, terminal illness (less than one-year life 
expectancy).  Evidence of bruising, bleeding, cellulitis and/or skin tears 
on the upper arms or abdomen. 
 
Study Type 
Single-centre, non-randomised study 
Date of First Enrolment 
TBC 
Target Sample Size 
30 
Objectives 
To investigate the pick-up of hypoglycaemic (and hyperglycaemic) 
episodes with the use of CGM in older people with diabetes 
presenting to hospital with falls and/or other symptoms suggestive 
of undetected hypoglycaemic episodes 
Outcomes 
Primary outcomes:  
• 
Proportion of participants with captured hypoglycaemia; 
within that group, the time spent in the hypoglycaemic range. 
Secondary outcomes:  
• 
Overall Time in Range; emergency department re-attendances 
and/or hospital re-admissions for falls, fractures, heart 
attacks, ischaemic strokes and death within 30 days. 

 
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Adverse events:  
• 
Pain and/or skin reactions at site of sensor insertion 

 
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1.4 Roles and responsibilities 
 
Protocol contributors 
Name 
Affiliation 
Role  
Professor Yoon Loke, 
Professor of Medicine 
and Pharmacology 
 
Norwich Medical 
School, UEA 
Initiated and developed the trial question and study 
development. 
Lead the writing of the protocol and funding 
application. 
Dr Katharina 
Mattishent, Clinical 
Lecturer in Older 
People’s Medicine 
 
Norwich Medical 
School, UEA 
Initiated and developed the trial question and study 
development. 
Contributed significantly to the drafting of the 
protocol and funding application. 
Dr Navena 
Navaneetharaja, 
Academic Clinical 
Fellow in Older 
People’s Medicine 
Norwich Medical 
School 
Contributed to the drafting of the protocol 
Dr Ketan Dhataryia, 
Consultant in 
Endocrinology and 
Diabetes 
Norfolk & 
Norwich 
University 
Hospital NHS 
Trust 
Contributions on the study design with emphasis on 
the clinical aspects of management of diabetes. 
 
Role of trial sponsor and funders 
Name 
Affiliation 
Role  
Trial sponsor   
University of 
East Anglia 
Approval of: trial design, data collection methods, 
conduct and monitoring with ultimate authority over 
these.  
Funder 
Norfolk 
Diabetes Trust 
(NDT) 
Approval of: trial design, data collection methods, 
conduct, monitoring and analysis. 
Funding the costs for the medical device used in this 
study (Dexcom G6). 
 
Trial Team 
Name 
Affiliation 
Role and responsibilities 
Dr Katharina 
Mattishent, Clinical 
Lecturer in Older 
People’s Medicine 
 
Norwich 
Medical School 
Chief investigator with responsibility for the: conduct, 
data analysis, interpretation and reporting. 
Recruitment of participants. 
Professor Yoon Loke, 
Professor of Medicine 
and Pharmacology 
 
Norwich 
Medical School 
Co-Chief investigator with overall responsibility for the: 
design, conduct, monitoring, analysis, interpretation 
and reporting of the trial. Recruitment of participants. 
Dr Navena 
Navaneetharaja, 
Academic Clinical 
Fellow in Older People’s 
Medicine 
Norwich 
Medical School 
Co-investigator - conduct and progress, responding to 
clinical inquiries, data analysis and interpretation and 
production of the final manuscript. 

 
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Dr Ketan Dhataryia, 
Consultant in 
Endocrinology and 
Diabetes 
Norfolk & 
Norwich 
University 
Hospital NHS 
Trust 
Clinical advisor on management of patients in the trial.  
Dr Sankalpa Neupane, 
Consultant in 
Endocrinology and 
Diabetes 
Norfolk & 
Norwich 
University 
Hospital NHS 
Trust 
 
Independent expert advisor - will provide independent 
advice on any adverse event reports or protocol 
deviations.  Dr Neupane has experience in running 
trials using CGM. 
 
 
 

 
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2 Flow diagram 
 
 
 
 
 
Participants will remain in the study for 10 days to 
2 weeks from providing consen
Receipt of information sheet whilst an inpatient 
at Norfolk and Norwich University Hospital or 
attending Older People’s Emergency Department.
If interested, the research team will fully explain 
the study and answer and questions. We will 
provide an introduction to using the CGM device.
We will give potential participants approximately 
two hours to consider whether or not to consent 
to take part
Consent will be taken
Sensor will be fitted and worn for up to 10 days.
DAY 5: the research team will contact the participant (or 
carer) to check how they are getting on with the CGM 
device and whether they are still happy to continue being 
part of the study.
DAY 10: members of the trial team will contact the participant to 
arrange a convenient time to remove the sensor and collect the 
smartphone
CGM data will be analysed by the research team
The research team will write to the individual 
participants’ GPs using the international 
consensus for clinical targets for CGM data 
interpretation
End of study

 
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3 Abbreviations 
 
Acute Medical Unit 
AMU 
Continuous glucose monitoring 
CGM 
Emergency Department 
ED 
Glycated haemoglobin 
HbA1c 
Norfolk Diabetes Trust 
NDT 
Older People’s Emergency Department 
OPED 
Sulfonylurea 
SU 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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4 Introduction 
4.1 Background and rationale 
What is the problem being addressed? 
Older people with diabetes often seek treatment in hospital for symptoms such as falls, 
dizziness or feeling muddled. These symptoms may potentially stem from (undiagnosed) 
episodes of hypoglycaemia that neither the patient nor the carers / healthcare professionals 
are aware of. My project aims to deliver 10 days of continuous glucose monitoring to check 
if recurrent hypoglycaemia may be an underlying cause that puts patients at risk of falls, 
dizziness and confusion. 
We regularly attend to patients these symptoms in the emergency department (ED)/Older 
People’s Emergency Department (OPED) and the Acute Medical Unit (AMU).  We usually 
order a battery of tests to find the underlying cause(s) but we currently do not have a good 
way of testing for recurrent hypoglycaemia in this vulnerable group. The actual reason for 
the falls and dizzy spells may remain unexplained, and patients are sent home without an 
exact diagnosis.  
In truth, most older patients are likely to have multiple contributing factors to their falls. We 
try to identify and remedy all underlying factors that put the patient at risk of falls.  We 
carry out a medication review (optimise sedative medication or anti-hypertensives) and 
check lying/standing blood pressures for postural hypotension.  Physiotherapists give falls 
advice and occupational therapists check whether any adjustments are needed in the home 
(eg stairlift, grab-rails, pendant alarms). 
In terms of monitoring, we request 24-hour heart monitoring if we suspect a possible 
problem with the heart. However, we have previously been unable to perform 24-hour 
glucose monitoring in older people with diabetes to check if low blood sugars are an 
important contributing factor to their falls and dizzy spells. 
Here, a significant issue is that commonly used blood tests (finger-prick monitoring and 
HbA1C) cannot reliably capture hypoglycaemia over a 24-hour period.  Use of continuous 
glucose monitoring (CGM) in research studies has unearthed far more hypoglycaemic 
episodes than previously thought.  A 5-day CGM study of 108 patients in Europe reported 

 
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that 49% had one or more hypoglycaemic episodes, and 75% of the patients were unaware 
that they had suffered from hypoglycaemia (1). 
A systematic review of CGM in older people found that hypoglycaemic episodes were 
detected in a sizeable proportion of participants, most of which were asymptomatic, with 
some patients spending nearly 2 hours per day in the hypoglycaemic range (2).   
In a feasibility trial of CGM in 12 older people with memory problems, nine participants 
were insulin users, of which six (66%) were found to be affected by hypoglycaemic events 
(some prolonged). The average duration of hypoglycaemic events ranged from 106 minutes 
to 437 minutes (3).  After reviewing the CGM data with a Consultant Diabetologist, we 
wrote to four participants’ GPs advising a change in their respective medication regimens.   
Hypoglycaemia can have devastating consequences on the lives of older people with 
diabetes. My research has demonstrated that hypoglycaemic episodes are associated with 
serious complications including heart attacks, stroke, falls, fractures, dementia and death (4, 
5). Randomised trial data of intensive versus standard diabetes therapy found that rigorous 
lowering of glucose led to significantly more hypoglycaemia, cardiovascular events and 
death. 
A large US study of 201705 adults with diabetes found several important factors for 
emergency admissions due to hypoglycaemia (6): 
• age >75 years 
• diabetes medications - insulin and/or sulfonylureas (SUs) 
• lower annual household income 
• number of comorbidities  
• HbA1c at either low or high end of range. 
 
Traditional monitoring of diabetes cannot reliably detect hypoglycaemia 
Intermittent finger-prick testing is the traditional method of monitoring blood glucose. It 
requires patients to recognize impending hypoglycaemia and initiate self-testing. This can 
be problematic in older people because they may have: 
1. Age-related physiological changes that mask symptoms of hypoglycaemia; 
2. Memory problems or decline in cognition; 

 
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3. Become confused/ drowsy with hypoglycaemia and cannot test; 
4. Nocturnal hypoglycaemia when asleep; 
5. Age-related physical changes making it difficult to conduct testing (poor vision, 
arthritis). 
The other commonly used blood test (HbA1c) only represents the average blood sugar value 
over the past two to three months as a single snapshot. It is used as a long-term marker of 
diabetes control e,g, NICE recommends HbA1C level of 53 mmol/mol (7.0%) for type 2 
diabetes (7).  What the HbA1c cannot provide is a detailed picture of individual daily glucose 
patterns and glucose variability.  For example, three people with diabetes could all have a 
HbA1C level of 53 mmol/mol (7.0%) but vastly different glucose variability.  This is illustrated 
in Table 1 and Figure 1, where a patient with ‘rollercoaster’ high and lows could have the 
same HbA1C as a very stable patient (8) (9). Similarly, finger-prick testing has poor temporal 
resolution and hypothetical four times daily testing could miss important hypo- and 
hyperglycaemic episodes (Figure 2). 
Table 1 
Example of 3 people with the same HbA1c, but different glucose variability 
 
Person A  
Person B  
Person C  
Above target range  
(>10mmol/L)  
40%  
25%  
0%  
In target range  
(3.9-10mmol/L)  
40%  
70%  
100%  
Below target range  
(<3.9mmol/L)  
20%  
5%  
0%  
HbA1C  
53mmol/mol (7.0%) 53mmol/mol (7.0%) 
 
53mmol/mol (7.0%) 
 
adapted from https://www.mysugr.com/en-us/blog/5-things-know-about-time-range/  
 
 
 
 
 
 

 
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Figure 1 
Example of 3 people with the same HbA1c, but different glucose variability 
 
 
 
 
 
 
 
Figure 2 
Example of glucose levels readings picked up by finger-prick testing (“glucometer readings”) 
versus CGM  
 
Continuous glucose monitoring (CGM) is a newer way to capture glucose levels, where the 
patient inserts a sensor just under the skin (either back of an arm or stomach).  The sensor 
measures interstitial glucose levels continuously (day and night) throughout its lifetime, 
which is usually around 10-14 days.   
Patients can access glucose recordings by swiping a reader over the sensor or through 
Bluetooth smartphones.  There are alarms if glucose levels go too high or low, as well as 
graphs displaying trends of rising or falling glucose levels.  The 24-hr glucose pattern is 
summarized, as are longer-term trends.  Users can consent to share data with carers, 
relatives or healthcare teams, with real-time updates about an individual’s glucose levels. 

 
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These data are absolutely vital for fine-tuning and avoiding harm from over-treatment with 
medication.   
Clinical targets for CGM have been produced by international experts (10).  For older 
people the recommendation is that they should spend less than 15 minutes in the 
hypoglycaemic range (below 3.9 mmol/L) and more than twelve hours between 3.9-10 
mmol/L (time in range). 
 
Funding for CGM in health service 
At present, the availability of CGM for older people with diabetes has not been a priority. In 
England, the National Health Service has prioritized CGM for patients with 
type 1 diabetes.  There is no explicit mention of CGM in older people with type 2 diabetes 
on medications (insulin, SUs) which carry a high risk of hypoglycaemia, and who may need 
carer support (for example due to underlying dementia) with diabetes management.   
 
Why is this research important in terms of improving the health and/or wellbeing of the 
public and/or to patients/service users, carers and health and care services? 
Patients and carers 
We know that hypoglycaemia in people with diabetes is associated with serious adverse 
events (cardiovascular events, falls, fractures, death)(5) and that hypoglycaemic episodes 
are underreported (11). 
We might be doing patients a disservice, if we fail to recognize that their symptoms are 
actually also due to hypoglycaemia, rather than other causes such as infection, stroke, 
postural hypotension etc.  Equally, we may discharge an older person with a diagnosis of 
“unexplained fall”, where we could have completely missed episodes of hypoglycaemia that 
contributed to the fall. 
Equally, the use of CGM can provide reassurance to a patient and/or carers if the data 
shows that large proportions of the day are spent between 3.9-10 mmol/L (time in range). 
From a feasibility study of older patients with diabetes and dementia, we know that 
caregivers felt safer when they were able to use CGM, and it was easier to measure glucose 
levels. 

 
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“…when [glucose level] was low and then when I then gave him something, it had then 
gone up so I knew it was working, so I was happy, more than happy with it.  Yes, I felt 
happy and I felt safer.”  
 
“…with the whole package of the […] dementia he’s not always understanding and 
doesn’t want it done and will pull his hand away and you know sometimes it’s just all too 
much”  (caregiver reporting difficulty of finger-prick test) . 
 
Healthcare utilization 
Existing evidence has demonstrated the high economic burden and healthcare utilization 
resulting from hypoglycaemia (12) (13, 14).  Hypoglycaemia has been identified as one of 
the top three preventable adverse drug events by the US Department of Health and Human 
Services (15).  In the US, serious hypoglycaemic episodes resulted in nearly 300,000 
emergency department (ED) visits in adults (15). Insulin is the second most common 
medication associated with ED visits or hospitalization (16).  Similar research in Asia found a 
10-fold increase in hospital admissions due to hypoglycaemic episodes in older people (17) 
(18). This upsurge has been attributed to increased intensity of medical treatment, as well 
as greater co-morbidities and frailty. 
There is also a large burden on ambulance services. The East Anglia emergency service 
hypoglycaemia programme recorded 62 referrals per week, with almost one-third of 
patients found unconscious (19).  In the East Midlands, the annual estimated costs of 
ambulance call-outs for hypoglycaemia is approximately £235,000 (20). 
 
Review of existing evidence  
Serious Consequences of hypoglycaemia in older people with diabetes 
The immediate effect of hypoglycaemia can be confusion, visual disturbance, alteration in 
mood and lack of concentration.  It also disrupts day-to-day activities, including exercise and 
driving. 
I conducted a large Clinical Practice Research Datalink cohort study examining the 
association of hypoglycaemia with serious adverse events in older people with dementia 
and diabetes. Patients with hypoglycaemia had substantially higher risks of death, 

 
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cardiovascular events, falls, fractures and emergency department attendances, than those 
who have not had a hypoglycaemic event (21). 
In addition, a systematic review and meta-analysis of 44 studies involving 2,507,434 
participants aged 55 and older (22)  confirmed significant associations between 
hypoglycaemia and the following serious adverse events: 
• Doubling in risk of death. 
• 50% increased risk of dementia. 
• 81% and 77% increased risk of macro- and microvascular complications respectively. 
• 78% and 68% increased risk in falls and fractures respectively. 
Studies assessing mortality also confirmed a time-response relationship with the highest risk 
of complications within 90 days after hypoglycaemia. 
 
Clinical impact of CGM guided management 
The Dexcom G6 CGM device was tested in an RCT of 99 patients within a US integrated 
healthcare setting. Almost half the patients were >65 years of age. Patients receiving CGM 
had significant reductions in emergency department visits and HbA1C compared to 
patients using finger-prick testing.  The authors recommend that replication in a larger RCT 
is needed (23). 
 
4.2 Explanation for choice of device 
This study will use Dexcom G6 (Dexcom, Inc., San Diego, CA) CGM (https://www.dexcom.com/en-
GB).  
 
Sensors last for 10 days and can be worn either on the back of an arm or the abdomen.  Interstitial 
glucose concentrations are measured every five minutes throughout the lifetime of a sensor.  The 
device does not require calibration with finger-stick readings.  In addition, there is no requirement to 
manually scan the sensor with a transmitter in order to obtain a reading.  In a previous feasibility 
study using a device which required scanning of the sensor to obtain readings, people with memory 
problems forgot to do so.  This meant that amount of data captured varied considerably between 
participants (range 3-92%; mean 55%) throughout the study period.  By using Dexcom G6, the trial 
team will overcome this as the glucose data is automatically sent to a Bluetooth equipped 
smartphone. This phone will be equipped with a data SIM to capture and transmit CGM findings to 
the research team. 

 
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4.3 Objectives 
This study will examine the use of a single 10-day period of CGM to detect hypoglycaemia in 
older people who present to hospital with falls and/or symptoms that could be attributed to 
hypoglycaemia.   
Being able to capture hypoglycaemia and time in range will enable a more informed 
medication review and subsequent adjustment of treatment to achieve safer control of 
diabetes (as advised by Consultant Diabetologist on research team).  This may then 
potentially lead to reduced ED visits, falls and reduce possible risk factors behind cognitive 
deterioration. 
 
4.4 Trial Design 
Single-centre, non-randomised study (no change in participants’ diabetes management 
during the study period). 
5 Methods 
5.1 Study setting 
Eligible participants will be identified and invited to participate whilst they either attend 
OPED or are admitted under AMU having presented with a fall or other symptoms 
suggestive of unrecognised hypoglycaemia. 
 
Participant Information Sheets will be handed out and interested patients will be consented 
by the research team.   
 
5.2 Participants 
5.2.1 Inclusion criteria 
75 years and older with diabetes on glucose-medications which carry a high risk 
of hypoglycaemia (sulfonylureas and/or insulin) presenting to hospital with a fall and/or 
symptoms suggestive of unrecognised hypoglycaemia (such as dizziness, feeling muddled). 
 

 
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5.2.2 Exclusion criteria 
Treatment with metformin only, lack of capacity, not willing to participate, terminal illness 
(less than one-year life expectancy).  Evidence of bruising, bleeding, cellulitis and/or skin 
tears on the upper arms or abdomen. 
 
5.3 Data Collection 
All participants will be issued with the Dexcom G6 device.  The trial team will buy the 
readers or smartphones and sensors and provide the participants with all the necessary 
equipment.  Participants will be shown how to wear the Dexcom G6 device, which they will 
be asked to wear for up to 10 days (=the lifespan of one sensor).   
 
There will be no change in the standard care of the participants’ diabetes management, 
during the study period. 
 
There will be no blinding of the glucose readings.  If participants and/or carers have any 
concerns about prolonged or recurrent glucose trends that indicate the patient is running 
significantly out of their individual target range, they can either contact their usual clinical 
team (e.g. GP or diabetes team) that provides their care, or alternatively alert the trial team 
(via a helpline) who will then assess the readings and make appropriate referrals. The trial 
team includes a Consultant in Diabetes, who will be able to evaluate glucose patterns and 
make recommendations for any further care through usual channels.  No adjustment to the 
diabetes medication should be made by the participants/carers, unless advised by a medical 
practitioner. 
 
The trial team will look at the data retrospectively (after the participant has worn the device 
for up to 10 days).  If, on retrospective review of the glucose data, there are clinically 
significant patterns of a participant spending a lot of time in the hypo/hyperglycaemic 
ranges, trial team will make recommendations to the participant’s healthcare team with 
regard to adjustments to the individual’s medication regime. 
 
5.4 Discontinuation 
Participation in this study is completely voluntary and participants can choose to 
discontinue at any stage. If so, they (or their nominated consultee) will be informed they: do 

 
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not need to give a reason (although they will be voluntarily asked to supply one) and that 
their medical and legal rights are not affected.   
 
5.5 Concomitant Care 
Whilst wearing the CGM device, participants will be advised to continue with the standard 
care for their diabetes as recommended by their healthcare team. 
 
5.6 Outcomes 
Primary outcomes:  
• Proportion of participants with captured hypoglycaemia; within that group, the time 
spent in the hypoglycaemic range. 
Secondary outcomes:  
• Overall Time in Range; emergency department re-attendances and/or hospital re-
admissions for falls, fractures, heart attacks, ischaemic strokes and death within 30 
days. 
5.7 Participants’ timeline 
Participants will remain in the study for 10 days to 2 weeks from providing consent: 
 
• Receipt of information sheet whilst an inpatient at Norfolk and Norwich University 
Hospital or attending Older People’s Emergency Department (OPED).  
• 
If interested, the research team will fully explain the study and answer and 
questions. The chief investigator will assess whether there is any evidence of bruising, 
bleeding, cellulitis and/or skin tears on the upper arms or abdomen.  Should that be 
the case, then the potential participant will not be eligible to take part in the study.  
We will provide an introduction to using the CGM device. 
• We will give potential participants approximately two hours to consider whether or 
not to consent to take part.  The CGM device will be used within its already approved 
licence and is supported by the NHS for people with diabetes, although older people 
generally do not qualify for NHS funding yet. 
• Consent will be taken. 
• Sensor will be fitted and worn for up to 10 days. 

 
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• After five days, the research team will contact the participant (or carer) to check how 
they are getting on with the CGM device and whether they are still happy to 
continue being part of the study.  If not, the participant will be withdrawn, however, 
the data collected by the CGM device up to the date of withdrawal will still be 
analysed.  The reason for withdrawal will be documented on the case record form 
(anonymised). 
• After wearing the sensor for 10 days, members of the trial team will contact the 
participant to arrange a convenient time to remove the sensor and collect the 
smartphone.  A member of the research team will travel to the place of residence to 
collect the equipment. When collecting the device, a member of the research team will stay 
outside the house, if this is preferred by the participant. 
• CGM data will be analysed by the research team.   
o There will be a cross-specialty review of the CGM data: Diabetes (Dhatariya), 
Older People’s Medicine (Mattishent) and Clinical Pharmacology (Loke). 
o The research team will write to the individual participants’ GPs using the 
international consensus for clinical targets for CGM data interpretation (10): 
§ If a participant spends around twelve hours between 3.9-10 mmol/L 
(time in range), then the research team will be able to provide 
reassurance regarding the current management regime. 
§ If a participant spends more than 15 minutes <3.9mmol/L (time below 
range), then the research team will make recommendations to adjust 
the medication regime to try and reduce the time spent in the 
hypoglycaemic range. 
§ If a participant spends more than 2 ½ hours per day >13.9 mmol/L (time 
above range), the research team will make recommendations to adjust 
the medication regime to try and reduce the time spent above range. 
• End of study. 
5.7.1 Withdrawal 
Participants will have the right to withdraw from the study at any time without giving 
reason. Identifiable data already collected with consent will be retained and used in the 
study. 

 
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5.7.2 Participant transfers 
If a participant moves from the area during the trial period, this will be considered a 
discontinuation from the study.  Identifiable data already collected with consent will be 
retained and used in the study. 
 
5.7.3 Trial closure 
Trial closure will be after the last participant has returned the CGM device. 
5.8 Sample size 
We aim to recruit up to 30 participants.  This is a size that the research team consider to be 
pragmatic and sufficient as indicative quantitative data upon which to base the sample size 
for a full trial. 
5.9 Recruitment 
 
Eligible participants will be identified and invited to participate whilst they either attend 
OPED or are admitted under AMU having presented with a fall or other symptoms 
suggestive of unrecognised hypoglycaemia. 
Participant Information Sheets (PIS) will be handed out and interested patients will be 
consented by the research team.  
No financial or non-financial incentives are offered to participants. 
5.10 Data collection 
Each participant will be given a unique trial Participant Identification Number (PIN). 
The preferred method of data collection is direct online entry of data by trial staff onto the 
central database, stored on servers based at the University of East Anglia. Data may be 
entered onto paper Case Record Forms (CRFs) prior to entry onto the database (but this is 
not essential).  
 
Data collection, data entry and queries raised by a member of the trial team will be 
conducted in line with the University of East Anglia’s Data Management Standard Operating 
Procedure. 
 

 
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Data for the primary outcome will be collected by downloading reports from the CGM 
device.  This will be done through the dedicated Dexcom G6 Clarity diabetes management 
software (available as a free download).  These reports will capture the glucose readings 
during the 10-day period when the CGM device was used.  
 
The research team will also collect the following patient data through access of hospital 
records: 
Baseline data: 
• Medication use at start of study period; 
• Baseline demographics and co-morbidities; 
• Duration of diabetes (if available from the notes); 
• HbA1c. 
Follow-up data: 
• ED attendances and/or hospital admissions for falls, fractures, heart attacks, 
ischaemic strokes and death within 30 days of removal of the participant’s sensor. 
 
Participant identification logs, screening logs and enrolment logs will be kept at the trial site 
in a locked cabinet within a secured room. Clinical trial team members will receive trial 
protocol training. Regular central monitoring will assess data quality and completeness 
during progression of the trial. All data will be handled in accordance with the Data 
Protection Act 1998. 
5.11 Data management 
All data will be stored in a database on a secure server, provided and maintained by the 
University. The server environment is protected by a firewall and is patched and maintained 
according to best practice. The physical location of the server is protected by CCTV and 
security door access. Access to the database will be controlled via unique, personally 
attributable (i.e. not generic) usernames, password protected, and accessible only to 
members of the trial team, and external regulators if requested.  
 
Data will be entered in the approved database by a member of the trial team.  After 
completion of the trial the database will be retained on the servers of University for on-

 
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going analysis.  The identification, screening and enrolment logs, linking participant 
identifiable data to the pseudo-anonymized PIN, will be stored securely at the database, 
with access controlled on a per-user basis. Access to identifiable and pseudo-anonymized 
data will be stored separately within the database and permissioned accordingly.  
Participant contact details will be collected by a member of the research team at the time 
that the participant calls to express an interest in being part of the study. 
 
5.12 Analysis plan 
Baseline characteristics for each participant will be presented in a Table.  For categorical 
variables, the number and percentage will be presented.  For continuous variables, the 
mean (and standard deviation) or median (and interquartile range) will be presented 
depending on the distribution. 
The aim of the study is to determine if the primary outcomes can be captured, and to obtain 
an idea of effect sizes and their boundaries.  This will inform conduct and design of future 
larger studies.  
For participants who commenced wearing the CGM device whilst an inpatient, the research 
team will analyse the inpatient data separately to data captured in the community. 
 
5.13 Data Monitoring 
5.13.1 Data Monitoring Committee 
This study is looking into the capture of hypoglycaemic episodes through the use of CGM in 
older people with diabetes.  It carries minimal or no risks.  The device simply enables 
glucose concentrations to be recorded in a less invasive and more frequent manner than 
conventional finger-prick testing.  
 
This study does not involve delivery of a therapeutic intervention that exerts physiological 
effect.  The medical device has already received CE mark/approval for people with diabetes 
and can be purchased from the Dexcom website: (https://www.dexcom.com/en-GB). 
 
Any adverse events reports will be assessed by the Independent Expert Advisor.  Therefore, 
the trial team submit that a separate data monitoring committee is not necessary. 

 
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5.13.2 Data monitoring for harm 
Adverse Event Definitions 
Adverse Event (AE) 
Any untoward medical occurrence in a patient or clinical 
trial participant administered a medicinal product and 
which does not necessarily have a causal relationship 
with this product. 
Adverse Reaction (AR) 
Any untoward and unintended response to an 
investigational medicinal product related to any dose 
administered 
Unexpected Adverse 
Reaction (UAR) 
An adverse reaction, the nature or severity of which is 
not consistent with the applicable product information 
(eg Investigator’s Brochure for an unauthorised product 
or summary of product characteristics (SPC) for an 
authorised product. 
Serious Adverse Event (SAE) 
or Serious Adverse Reaction 
(SAR) 
Any AE or AR that: 
results in death  
is life threatening*  
requires hospitalisation or prolongs existing 
hospitalisation** 
results in persistent or significant disability or incapacity 
or is another important medical condition*** 
* the term life threatening here refers to an event in which the patient is at risk of death 
at the time of the event; it does not refer to an event that might hypothetically cause 
death if it was more severe (eg a silent myocardial infarction) 
** Hospitalisation is defined as an in-patient admission, regardless of length of stay, even 
if the hospitalisation is a precautionary measure for continued observation. 
Hospitalisation for pre-existing conditions (including elective procedures that have not 
worsened) do not constitute an SAE 
*** Medical judgement should be exercised in deciding whether an AE or AR is serious in 
other situations. Important AEs or ARs that may not be immediately life threatening or 
result in death or hospitalisation, but may seriously jeopardise the participant by 
requiring intervention to prevent one of the other outcomes listed in the table  
 
Adverse events include: pain at the insertion site of the sensor, skin reaction to the adhesive 
of the sensor. 
 
All non-serious AEs and ARs, whether expected or not, should be recorded in the patient’s 
medical notes and reported in the toxicity (symptoms) section of the Follow-up Form. SAEs 
and SARs should be notified immediately the investigator becomes aware of the event (in 
no circumstance should this notification take longer than 24 hours). 
 

 
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When an AE or AR occurs, the investigator responsible for the care of the participant must 
first assess whether or not the event is serious using the definition given in Table 1. If the 
event is classified as ‘serious’ then an SAE form must be completed and notification sent 
within one working day. 
 
The investigator must assess the causality of all serious events or reactions in relation to the 
trial therapy using the definitions below.  
 
Causality definitions 
Relationship 
Description 
Event type 
Unrelated 
There is no evidence of any causal 
relationship 
Unrelated SAE 
Unlikely to be related 
There is little evidence to suggest that 
there is a causal relationship (eg the event 
did not occur within a reasonable time 
after administration of the trial 
medication). There is another reasonable 
explanation for the event (eg the 
participant’s clinical condition or other 
concomitant treatment) 
Unrelated SAE 
Possibly related 
There is some evidence to suggest a 
causal relationship (eg because the event 
occurs within a reasonable time after 
administration of the trial medication). 
However, the influence of other factors 
may have contributed to the event (eg the 
participant’s clinical condition or other 
concomitant treatment)  
SAR 
Probably related 
There is evidence to suggest a causal 
relationship and the influence of other 
factors is unlikely 
SAR 
Definitely related 
There is clear evidence to suggest a causal 
relationship and other possible 
contributing factors can be ruled out. 
SAR 
 
5.14 Trial team 
The Trial Team will be set up to assist with developing the design, co-ordination and day to 
day operational issues in the management of the trial, including budget management. 

 
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5.15 Independent Expert Advisor 
The Independent Expert Advisor is the independent advisor responsible for oversight of the 
trial to safeguard the interests of trial participants.  
 
5.16 Trial Sponsor 
The role of the sponsor is to take on responsibility for securing the arrangements to initiate, 
manage and finance the trial.  
6 Ethics and Dissemination 
6.1 Research Ethics Approval 
Before initiation of the trial, the protocol, all informed consent/declaration forms and any 
material given to the prospective participant/consultee will have been approved by the 
relevant REC. Any subsequent amendments to these documents will be submitted for 
further approval.  
 
The rights of the participant to refuse to participate in the trial without giving a reason will 
be respected.  The participant remains free to change their mind at any time about the 
protocol treatment and follow-up without giving a reason and without prejudicing their 
further treatment. 
6.2 Protocol Amendments 
The chief investigator is responsible for communicating any regulatory approved substantial 
protocol amendments (e.g. changes to eligibility criteria, outcomes, sample size calculations, 
analyses) to all principal investigators in all participating centres, trial registries, journals and 
regulators.  Relevant parties will be informed by postal letter containing an amended 
version of the protocol for storing in the trial master file. 
6.3 Consent or Consultation 
Patients will be provided with a Participant Information Sheet (PIS) and given time to read it 
fully.  Following a discussion with a medical qualified investigator or suitably trained and 
authorised delegate, any questions will be satisfactorily answered and if the participant is 
willing to participate, written informed consent will be obtained.  
 

 
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Members of the trial team seeking consent will be fully trained in Good Clinical Practice 
(GCP). During the consent process, it will be made completely and unambiguously clear to 
participants they are free to refuse to participate in all or any aspect of the trial, at any time 
and for any reason, without incurring any penalty or affecting their treatment.  
 
A copy of the approved consent form is available from the trial team. 
6.4 Confidentiality 
All patients will be recorded on an identification log with pseudo-anonymised identifiers of 
initials and trial ID.  This log will be compiled by trial research staff and stored in either 
locked cabinets in swipe card access officers and on hospital or university password access 
computers in swipe card access offices.  All potential participants are allocated a participant 
identification number (PIN) to replace their name. Personal information is collected by trial 
staff trained in the principals of GCP. Only members of the trial team will have access to the 
database, identification and screening logs. 
6.5 Declaration of Interests 
The investigators named on the protocol have no financial or other competing interests that 
impact on their responsibilities towards the scientific value or potential publishing activities 
associated with the trial.  
6.6 Indemnity 
UEA holds insurance to cover participants for injury caused by their participation in the 
clinical trial. Participants may be able to claim compensation if they can prove that UEA has 
been negligent.  
 
Participants may also be able to claim compensation for injury caused by participation in 
this clinical trial without the need to prove negligence on the part of UEA or another party.  
Participants who sustain injury and wish to make a claim for compensation should do so in 
writing in the first instance to the Chief Investigator, who will pass the claim to UEA’s 
insurers, via the Sponsor’s office. 

 
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6.7 Finance 
This study is funded by the Norfolk Diabetes Trust (NDT).  It is not expected that any further 
external funding will be sought 
6.8 Archiving 
The investigators agree to archive and/or arrange for secure storage of trial materials and 
records for a minimum of 10 years after the close of the trial. 
6.9 Access to data 
Access to the final trial dataset will be granted to the trial team, the independent expert 
advisor and any regulatory authorities. Access by any other parties will require approval 
from the CI and the independent advisor.   Requests for access to trial data will be 
considered, and approved in writing where appropriate, after formal application to the 
independent expert advisor. 
6.10 Ancillary and post-trial care 
Following completion of the trial, CGM will not be prescribed to participants using research 
funding.  Patients and carers will have to go through conventional funding channels if they 
wish to continue using the medical device. 
6.11 Publications policy 
The Chief Investigator will co-ordinate the writing of abstracts and full publications and send 
these to all co-investigators before submission to scientific meetings and peer review 
journals for comments and approval.  Following full publication, relevant papers will be sent 
to the appropriate patient groups, and participants who have requested this. 
 
Any trial related publications will include co-investigators, who in the opinion of the Chief 
Investigator, have made a significant contribution to the: design, conduct, analysis, funding 
application and report writing of the trial.    
 
 
 

 
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7 Protocol Amendments 
 

 
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