Diabetes Mellitus, Type 1FLASH-UKNCT03815006
Flash-glucose Monitoring in Sub-optimally Controlled Type 1 Diabetes (FLASH-UK)
A study testing Free Style Libre 2 in people with Diabetes Mellitus, Type 1, run by Manchester University NHS Foundation Trust at 8 sites in United Kingdom.
Trial summary
FreeStyle Libre (FSL2) is a novel glucose monitoring device (Flash glucose monitoring) in the form of a disc worn on the arm for 14 days, and a hand-held reader which is designed to largely replace the recommended 4-10 painful finger-stick blood glucose tests required each day for the self-management of type 1… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Free Style Libre 2
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 8 sitesUnited Kingdom
- Study dates
- 9 Jan 2020to 10 Oct 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The participant is ≥16 years old
- The participant has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative if duration of diabetes is < 1 years
- Participant is treated with insulin pump or multiple daily injection for at least 12 weeks and no plans to change treatment modality during next 28 weeks
- The participant is literate in English for safe study conduct
- Screening HbA1c ≥ 7.5% (58.5mmol/mol) and ≤ 11% (97 mmol/mol) based on analysis from local laboratory
- The participant is willing to wear study glucose sensor and scan for glucose levels at regular intervals
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- The participant is willing to follow study specific instructions and improve glucose control
- Female participants of child bearing age should be on effective contraception and must have a negative blood or urine pregnancy test at screening.
- The participant adopting a virtual pathway through the trial is able and willing to post study devices, questionnaires and blood collection kits back to the research team or to the laboratory using pre-paid postal services.
- The participant adopting a virtual pathway through the trial has internet connection, appropriate videoconferencing software and supporting devices to undertake video consultations where necessary.
Who cannot join
- Non-type 1 diabetes mellitus including those secondary to chronic disease
- Any other physical disease or people with known severe mental illness (psychotic disorder, bipolar disorder, dementia, substance and alcohol dependence, learning disabilities, depression with active suicidal ideation) which are likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- Current users of real-time glucose monitoring sensors or flash-glucose monitoring for more than 4 weeks within last 12 weeks
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, SGLT2 inhibitors, GLP-1 agonists, Pramlinatide, non-selective beta-blockers and MAO inhibitors etc.(patients on stable metformin is not an exclusion)
- Known or suspected allergy against insulin
- Severe visual impairment
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- Complete loss of hypoglycaemia awareness
- Significant renal impairment eGFR<30 within previous one year or on dialysis or active retinopathy (defined as presence of maculopathy or proliferative changes) as judged by the investigator
- More than one episode of severe hypoglycaemia as defined by American Diabetes Association (30) in preceding 24 weeks
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United Kingdom8 sites
College of Medical and Dental Sciences University of Birmingham
Birmingham, B152TT
Addenbrooke's Hospital
Cambridge, CB20QQ
University Hospitals of Derby and Burton NHS Foundation Trust
Derby, DE223NE
Ipswich Hospital
Ipswich, IP4 5PD
Manchester University NHS Foundation Trust
Manchester, M139WL
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, NR47UY
The Adam Practice
Poole, Dorset, BH16 5PW
Queen Alexandra Hospital
Portsmouth, PO63LY
About this study
Official title: An Open-label, Multi-centre, Randomised, Parallel Design Study to Assess the Efficacy of Flash Glucose Monitoring in Adults With Sub-optimally Controlled Type 1 Diabetes.
FreeStyle Libre (FSL2) is a novel glucose monitoring device (Flash glucose monitoring) in the form of a disc worn on the arm for 14 days, and a hand-held reader which is designed to largely replace the recommended 4-10 painful finger-stick blood glucose tests required each day for the self-management of type 1 diabetes. The purpose of this study is to determine whether flash glucose monitoring with FSL2 device will improve HbA1c over 24 weeks compared to self-monitoring of blood glucose in adults and adolescents (16 or older) with sub-optimally controlled (HbA1c 7.5% to 11%) type 1 diabetes.
This is an open-label, multi-centre, randomised, parallel design study, involving a 2-week run-in period, followed by a 24-week study period during which participants will use either FSL2 or continue usual finger-stick glucose monitoring in random order. A total of up to 156
Read more
randomised participants from up to 180 recruited aged 16 years and older with T1D on insulin pump therapy or multiple daily injection therapy were recruited through diabetes clinics in participating centres.
Participants will receive appropriate training to maximise the benefits of FSL2 and finger-stick glucose levels in self-management. The primary outcome is the difference in HbA1c between the two groups at 24 weeks. Secondary outcomes are time spent with glucose levels above and below target, as recorded by FSL2, and other flash glucose-based metrics. Impact on quality of life, diabetes distress, mood, needle burden, disordered eating and treatment satisfaction will also be undertaken. Relative cost-effectiveness of FSL2 device compared with self-monitoring will also be assessed from a UK NHS perspective.
Read the detailed description
Study Design:
An open-label, multi-centre, randomised, parallel study, in adults and adolescents (16 years and older) with type 1 diabetes and sub-optimal glycaemic control (HbA1c 7.5% to 11%), either on insulin pump treatment or multiple daily injections, contrasting flash glucose monitoring using FreeStyle Libre 2 device with traditional finger-stick glucose monitoring for 24 weeks. Expecting approximately 15% to 20% dropout rate recruitment will aim for 180 participants aiming for 156 randomised and 128 completed participants.
Participant Recruitment:
This is a UK multi-centre and recruitment will take place at the following centres:
- Diabetes Centres within Manchester University Foundation Trust
- Royal Derby Hospital, Derby
- Queen Elizabeth Hospital, Birmingham
- Addenbrookes Hospital, Cambridge
- Norfolk and Norwich University Hospital, Norwich
- Queen Alexandra Hospital, Portsmouth
- Ipswich Hospital
- The Adam Practice, Dorset
Each centre will aim to recruit between 25 to 30 participants. Additional diabetes centres surrounding above hospitals may act as participant identification centres. Potential participants will be identified by their treating clinicians and invited to contact the research team. They will be sent the study information leaflets and an invitation by post or in-person to join the study by the research team at least one day before the recruitment visit. The study may also be advertised via social media.
After recruitment, consent, subjects will be randomised for 24-weeks home use of flash-glucose monitoring or 24-weeks use finger-stick glucose monitoring.
Study Visits:
The study includes up to 7 visits for participants completing the study. Maximum time in study is 30 weeks. Each study visit can be scheduled with +/- 2 weeks of the planned visit date.
Visit 1: Recruitment Visit and Screening Assessment
Once the participants have agreed to participate in the study, they will be invited for the recruitment visit, and given a participant ID, when the following activities will be performed by the research team:
- written informed consent/assent
- checking inclusion and exclusion criteria
- medical and diabetes history including the presence of diabetes complications and hypoglycaemia burden
- ethnicity, body weight and height measurement; calculation of BMI
- record of current insulin therapy
- urine or blood pregnancy test (females of child-bearing potential)
- record of occupation and educational attainment
- any history of disordered eating or needle phobia
- previous participation in structured education, the status of carb counting, use of bolus calculator
Screening Blood Sampling
Blood samples will be taken to measure HbA1c (measured at the local laboratory if not done within the last two weeks). Renal and Thyroid function will also be evaluated (if not done in last one year). Less than 15 ml of whole blood will be taken from each participant.
Questionnaires at screening
Evaluation of participants' responses in terms of quality of life, diabetes distress, needle burden, disordered eating, depression and diabetes treatment satisfaction using
- EQ-5DL-5L questionnaire
- Type 1 Diabetes Distress Scale (DDS),
- Diabetes fear of injecting and self-testing (D-FISQ) questionnaire,
- Diabetes Eating Problem Survey (DEPS-R),
- Diabetes Treatment Satisfaction Questionnaire (DTSQ),
- Patient Health Questionnaire (PHQ-9) and
- The Glucose Monitoring Satisfaction Survey (GMSS).
- Hypoglycaemia burden will be assessed using Clarke questionnaire and Gold score.
Visit 2: Insertion of the blinded glucose monitoring device
Purpose of visit 2 is to insert a blinded glucose monitor (FreeStyle Libre Pro device). The participant will be provided with instructions about using this device for the next two weeks. Visit two may be combined with visit 1.
Visit 3: Adherence assessment, randomisation and the start of study treatment
During Visit 3, participant's adherence/tolerance of using the flash-CGM over preceding 14 days will be assessed. To proceed with the study participant should have worn the blinded glucose monitoring device for at least ten days' during the last 14 days of the run-in period. If the participant fails to demonstrate adherence or develops any significant allergy or intolerance to the glucose sensor, the study will be terminated, and the participant will be removed from the study. Participant randomisation for the treatment intervention will take place during visit 3.
Initiation of study treatment The participant will arrive at the clinical facility or clinic at the agreed time. Body weight measurement will be made. Participants will be provided with necessary training on the use of study devices according to randomisation.
Training session Participants randomised to flash-glucose monitoring arm will receive education and training about insertion and initiation of the sensor as well as how to use flash-glucose monitoring data for treatment optimisation. They will be encouraged to download data at home to identify pattern recognition. This session will be conducted by a professional diabetes educator or a member of the study team. Education will be tailored to meet the needs of the individual. Participants randomised to conventional finger-stick glucose monitoring arm will be encouraged to use finger-stick glucose levels to optimise treatment and will receive education about insulin dose adjustments using finger-stick glucose levels. The study will try to mimic real-life conditions by continuing participants pre-study diabetes treatment unchanged and finger-stick glucose testing frequency as determined by the participant as required. Participants in both arms will also receive training on sick day rules and dealing with hypo and hyperglycaemia. Participants will be provided with a paper diary to collect information about insulin doses and carbohydrate intake in the last three days of each study month.
Visit 4: (+4 weeks since randomisation): Review data and treatment optimisation Purpose of this visit is to review data from Flash-glucose monitoring and finger-stick glucose monitoring to further optimise treatment. Study devices will be downloaded. Information about insulin doses and any adverse events will be collected.
Visit 5: (+12 weeks since randomisation): Review data and treatment optimisation
Purpose of this visit is to review data from Flash-glucose monitoring and finger-stick glucose monitoring to further optimise treatment. Study devices will be downloaded. Information about insulin doses, participant diaries and any adverse events will be collected. A blood sample will be collected for HbA1c.
Visit 6: (+22 weeks since randomisation): Finger-stick glucose monitoring arm only
Participants randomised to finger-stick glucose monitoring arm will have an extra visit ten weeks after visit 5 to insert a blinded glucose sensor for data capture.
Visit 7: (+24 weeks since randomisation): End of randomised study treatment
The participant will be invited to attend the research centre approximately 12 weeks after Visit 5. This would be the end of 24 weeks randomised study period. All study devices will be downloaded. Insulin usage data will be recorded and diaries collected. The participant will have a blood test for the HbA1c. Body weight measurement will be made. The participant will be asked to complete the same questionnaires completed at Visit 1. In addition, participants in the FSL2 arm will be asked to complete a additional questionnaire exploring expectations and experience of using FSL2 during the study. A subset of participants (n=40 aiming for 25 completed questionnaires) in the FSL2 arm and subset of researchers (n=10) will also be asked to complete additional questionnaires to help with the process evaluation.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Free Style Libre 2
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Free Style Libre 2Device
FreeStyle Libre 2 (FSL2) is a novel glucose monitoring device (Flash glucose monitoring) in the form of a disc worn on the arm for 14 days and a hand-held reader which is designed to largely replace the recommended 4-10 painful finger-stick blood glucose tests required each day for the self-management of type 1 diabetes (T1D).
| Study group | Role | What they receive |
|---|---|---|
| Free Style Libre 2 device | Experimental | At the start, a blood sample will be taken for the measurement of HbA1c. Training and education on the use of FSL2 will be provided by the research team. Participants will be advised to use flash glucose monitoring continuously for the next 24 weeks. Receives: Device: Free Style Libre 2 |
| Self-monitoring of blood glucose | No intervention | At the start, a blood sample will be taken for the measurement of HbA1c. Masked FSL will be applied for two weeks, during the last two weeks of control period. Education will focus on using fingerstick measurement for treatment optimisation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
HbA1c Level at 24 Weeks
The primary outcome is difference in HbA1c between the two groups at 24 weeks.
Measured: 24 weeks
Secondary outcomes (30)
HbA1c Level at 12 Weeks
This is the difference in HbA1c between the two groups at 12 weeks
Measured: 12 weeks
Percentage With HbA1c ≤ 53 mmol/Mol (7.0%) at 12 Weeks
This is the comparison between arms of percentage with HbA1c ≤ 53 mmol/mol (7.0%) at 12 weeks
Measured: 12 weeks
Percentage With HbA1c ≤ 53 mmol/Mol (7.0%) at 24 Weeks
This is the comparison between arms of percentage with HbA1c ≤ 53 mmol/mol (7.0%) at 24 weeks
Measured: 24 weeks
Sensor Based - Time Spent in the Target Glucose Range Between 3.9 to 10.0 mmol/l
Time spent in the target glucose range between 3.9 to 10.0 mmol/l (70 to 180mg/dl).
Measured: 24 weeks
Sensor Based - Time Spent Below Target Glucose (<3.9mmol/l)
Time spent below target glucose (<3.9mmol/l) (<70mg/dl)
Measured: 24 weeks
Sensor Based - Time Spent Above Target Glucose (10.0 mmol/l)
Time spent above target glucose (10.0 mmol/l) (180 mg/dl)
Measured: 24 weeks
Sensor Based - Average Glucose Levels
Average glucose levels
Measured: 24 weeks
Sensor Based - Standard Deviation Glucose Levels
Standard deviation glucose levels
Measured: 24 weeks
Sensor Based - Coefficient of Variation Glucose Levels
Coefficient of variation glucose levels
Measured: 24 weeks
Sensor Based - Time With Sensor Glucose Levels < 3.5 mmol/l
The time with sensor glucose levels < 3.5 mmol/l (63 mg/dl)
Measured: 24 weeks
Sensor Based - Time With Sensor Glucose Levels < 3.5 mmol/l
The time with sensor glucose levels < 3.0 (54mg/dl)
Measured: 24 weeks
Sensor Based - Time With Sensor Glucose Levels < 2.8 mmol/l
The time with sensor glucose levels < 2.8 mmol/l (50 mg/dl)
Measured: 24 weeks
Sensor Based - Time With Sensor Glucose Levels in the Significant Hyperglycaemia
The time with sensor glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)
Measured: 24 weeks
Sensor Based - AUC of Glucose Below 3.0mmol/l
AUC of glucose below 3.0mmol/l (54mg/dl)
Measured: 24 weeks
Total Daily Average Insulin Dose
Comparison between arms of Total daily average insulin dose
Measured: 24 weeks
Daily Average Basal Insulin Dose
Comparison between arms of Daily average basal insulin dose
Measured: 24 weeks
Daily Average Bolus Dose
Comparison between arms of Daily average bolus dose
Measured: 24 weeks
Average Number of Boluses of Rapid Acting Insulin
Average number of boluses of rapid acting insulin per day
Measured: 24 weeks
Number of Freestyle Libre Scans Per Day
Number of Freestyle Libre scans per day in the intervention arm only
Measured: 24 weeks
Frequency of Severe Hypoglycaemic Episodes
Frequency of severe hypoglycaemic episodes as defined by American Diabetes Association
Measured: 24 weeks
Frequency of Significant Ketosis Events
Frequency of significant ketosis events (plasma ketones >3mmol/l)
Measured: 24 weeks
Nature and Severity of Other Adverse Events
Nature and severity of other adverse events.
Measured: 24 weeks
Type 1 Diabetes Distress Scale Score
Type 1 Diabetes Distress Scale score compared between arms
Measured: 24 weeks
EQ-5D-5L Quality of Life Questionnaire Score
EQ-5D-5L Quality of Life questionnaire
Measured: 24 weeks
Patient Health Questionnaire Score
Patient Health Questionnaire: score of 5-9 would be minimal symptoms. any score large than 20 would be categorised as severe major depression
Measured: 24 weeks
Diabetes Fear of Injecting and Self-Testing Questionnaire Score
Diabetes fear of injecting and self-testing questionnaire: 15 questions, 6 for Fear of Self injecting, 9 for fear of self testing.
Measured: 24 weeks
The Revised Diabetes Eating Problem Survey Score
The revised Diabetes Eating Problem Survey
Measured: 24 weeks
Average Number of Days of Libre Usage Per Week
Average number of days of usage per week
Measured: 24 weeks
Diabetes Treatment Satisfaction Questionnaire Score
Diabetes Treatment Satisfaction Questionnaire
Measured: 24 weeks
Glucose Monitoring Satisfaction Survey Score
Glucose Monitoring Satisfaction Survey: 15 questions ranging from 1-5.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start9 Jan 2020
- Primary completion10 Oct 2021
- Study completion10 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Collaborators
- University Hospitals of Derby and Burton NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Portsmouth Hospitals NHS Trust, University Hospital Birmingham NHS Foundation Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, University of Manchester, Diabetes UK, Clinical Trials Unit, Manchester, BHR Limited, East Suffolk and North Essex NHS Foundation Trust, The Adam Practice
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03815006
- Sponsor's protocol ID
- B00373
- Acronym
- FLASH-UK
- Status last verified
- Dec 2022
- First submitted
- 11 Jan 2019
- Last updated
- 16 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the primary study manuscript after deidentification (text, tables, figures, and appendices).
Publications
Leelarathna L, Wilmot EG. Flash forward: a review of flash glucose monitoring. Diabet Med. 2018 Apr;35(4):472-482. doi: 10.1111/dme.13584. Epub 2018 Feb 27.
PubMed 29356072Leelarathna L, Evans ML, Neupane S, Rayman G, Lumley S, Cranston I, Narendran P, Barnard-Kelly K, Sutton CJ, Elliott RA, Taxiarchi VP, Gkountouras G, Burns M, Mubita W, Kanumilli N, Camm M, Thabit H, Wilmot EG; FLASH-UK Trial Study Group. Intermittently Scanned Continuous Glucose Monitoring for Type 1 Diabetes. N Engl J Med. 2022 Oct 20;387(16):1477-1487. doi: 10.1056/NEJMoa2205650. Epub 2022 Oct 5.
PubMed 36198143Wilmot EG, Evans M, Barnard-Kelly K, Burns M, Cranston I, Elliott RA, Gkountouras G, Kanumilli N, Krishan A, Kotonya C, Lumley S, Narendran P, Neupane S, Rayman G, Sutton C, Taxiarchi VP, Thabit H, Leelarathna L. Flash glucose monitoring with the FreeStyle Libre 2 compared with self-monitoring of blood glucose in suboptimally controlled type 1 diabetes: the FLASH-UK randomised controlled trial protocol. BMJ Open. 2021 Jul 14;11(7):e050713. doi: 10.1136/bmjopen-2021-050713.
PubMed 34261691
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-centre, Randomised, Parallel Design Study to Assess the Efficacy of Flash Glucose Monitoring in Adults With Sub-optimally Controlled Type 1 Diabetes.
- ClinicalTrials.gov ID
- NCT03815006
- Acronym / sponsor ID
- FLASH-UK / B00373
- Conditions
- Diabetes Mellitus, Type 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Collaborators
- University Hospitals of Derby and Burton NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Portsmouth Hospitals NHS Trust, University Hospital Birmingham NHS Foundation Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, University of Manchester, Diabetes UK, Clinical Trials Unit, Manchester, BHR Limited, East Suffolk and North Essex NHS Foundation Trust, The Adam Practice
- Study start
- 9 Jan 2020 (actual)
- Primary completion
- 10 Oct 2021 (actual)
- Study completion
- 10 Oct 2021 (actual)
- First posted
- 24 Jan 2019 (actual)
- Results
- Posted 16 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
FreeStyle Libre (FSL2) is a novel glucose monitoring device (Flash glucose monitoring) in the form of a disc worn on the arm for 14 days, and a hand-held reader which is designed to largely replace the recommended 4-10 painful finger-stick blood glucose tests required each day for the self-management of type 1 diabetes. The purpose of this study is to determine whether flash glucose monitoring with FSL2 device will improve HbA1c over 24 weeks compared to self-monitoring of blood glucose in adults and adolescents (16 or older) with sub-optimally controlled (HbA1c 7.5% to 11%) type 1 diabetes.
This is an open-label, multi-centre, randomised, parallel design study, involving a 2-week run-in period, followed by a 24-week study period during which participants will use either FSL2 or continue usual finger-stick glucose monitoring in random order. A total of up to 156
randomised participants from up to 180 recruited aged 16 years and older with T1D on insulin pump therapy or multiple daily injection therapy were recruited through diabetes clinics in participating centres.
Participants will receive appropriate training to maximise the benefits of FSL2 and finger-stick glucose levels in self-management. The primary outcome is the difference in HbA1c between the two groups at 24 weeks. Secondary outcomes are time spent with glucose levels above and below target, as recorded by FSL2, and other flash glucose-based metrics. Impact on quality of life, diabetes distress, mood, needle burden, disordered eating and treatment satisfaction will also be undertaken. Relative cost-effectiveness of FSL2 device compared with self-monitoring will also be assessed from a UK NHS perspective.
Detailed description
Study Design:
An open-label, multi-centre, randomised, parallel study, in adults and adolescents (16 years and older) with type 1 diabetes and sub-optimal glycaemic control (HbA1c 7.5% to 11%), either on insulin pump treatment or multiple daily injections, contrasting flash glucose monitoring using FreeStyle Libre 2 device with traditional finger-stick glucose monitoring for 24 weeks. Expecting approximately 15% to 20% dropout rate recruitment will aim for 180 participants aiming for 156 randomised and 128 completed participants.
Participant Recruitment:
This is a UK multi-centre and recruitment will take place at the following centres:
- Diabetes Centres within Manchester University Foundation Trust
- Royal Derby Hospital, Derby
- Queen Elizabeth Hospital, Birmingham
- Addenbrookes Hospital, Cambridge
- Norfolk and Norwich University Hospital, Norwich
- Queen Alexandra Hospital, Portsmouth
- Ipswich Hospital
- The Adam Practice, Dorset
Each centre will aim to recruit between 25 to 30 participants. Additional diabetes centres surrounding above hospitals may act as participant identification centres. Potential participants will be identified by their treating clinicians and invited to contact the research team. They will be sent the study information leaflets and an invitation by post or in-person to join the study by the research team at least one day before the recruitment visit. The study may also be advertised via social media.
After recruitment, consent, subjects will be randomised for 24-weeks home use of flash-glucose monitoring or 24-weeks use finger-stick glucose monitoring.
Study Visits:
The study includes up to 7 visits for participants completing the study. Maximum time in study is 30 weeks. Each study visit can be scheduled with +/- 2 weeks of the planned visit date.
Visit 1: Recruitment Visit and Screening Assessment
Once the participants have agreed to participate in the study, they will be invited for the recruitment visit, and given a participant ID, when the following activities will be performed by the research team:
- written informed consent/assent
- checking inclusion and exclusion criteria
- medical and diabetes history including the presence of diabetes complications and hypoglycaemia burden
- ethnicity, body weight and height measurement; calculation of BMI
- record of current insulin therapy
- urine or blood pregnancy test (females of child-bearing potential)
- record of occupation and educational attainment
- any history of disordered eating or needle phobia
- previous participation in structured education, the status of carb counting, use of bolus calculator
Screening Blood Sampling
Blood samples will be taken to measure HbA1c (measured at the local laboratory if not done within the last two weeks). Renal and Thyroid function will also be evaluated (if not done in last one year). Less than 15 ml of whole blood will be taken from each participant.
Questionnaires at screening
Evaluation of participants' responses in terms of quality of life, diabetes distress, needle burden, disordered eating, depression and diabetes treatment satisfaction using
- EQ-5DL-5L questionnaire
- Type 1 Diabetes Distress Scale (DDS),
- Diabetes fear of injecting and self-testing (D-FISQ) questionnaire,
- Diabetes Eating Problem Survey (DEPS-R),
- Diabetes Treatment Satisfaction Questionnaire (DTSQ),
- Patient Health Questionnaire (PHQ-9) and
- The Glucose Monitoring Satisfaction Survey (GMSS).
- Hypoglycaemia burden will be assessed using Clarke questionnaire and Gold score.
Visit 2: Insertion of the blinded glucose monitoring device
Purpose of visit 2 is to insert a blinded glucose monitor (FreeStyle Libre Pro device). The participant will be provided with instructions about using this device for the next two weeks. Visit two may be combined with visit 1.
Visit 3: Adherence assessment, randomisation and the start of study treatment
During Visit 3, participant's adherence/tolerance of using the flash-CGM over preceding 14 days will be assessed. To proceed with the study participant should have worn the blinded glucose monitoring device for at least ten days' during the last 14 days of the run-in period. If the participant fails to demonstrate adherence or develops any significant allergy or intolerance to the glucose sensor, the study will be terminated, and the participant will be removed from the study. Participant randomisation for the treatment intervention will take place during visit 3.
Initiation of study treatment The participant will arrive at the clinical facility or clinic at the agreed time. Body weight measurement will be made. Participants will be provided with necessary training on the use of study devices according to randomisation.
Training session Participants randomised to flash-glucose monitoring arm will receive education and training about insertion and initiation of the sensor as well as how to use flash-glucose monitoring data for treatment optimisation. They will be encouraged to download data at home to identify pattern recognition. This session will be conducted by a professional diabetes educator or a member of the study team. Education will be tailored to meet the needs of the individual. Participants randomised to conventional finger-stick glucose monitoring arm will be encouraged to use finger-stick glucose levels to optimise treatment and will receive education about insulin dose adjustments using finger-stick glucose levels. The study will try to mimic real-life conditions by continuing participants pre-study diabetes treatment unchanged and finger-stick glucose testing frequency as determined by the participant as required. Participants in both arms will also receive training on sick day rules and dealing with hypo and hyperglycaemia. Participants will be provided with a paper diary to collect information about insulin doses and carbohydrate intake in the last three days of each study month.
Visit 4: (+4 weeks since randomisation): Review data and treatment optimisation Purpose of this visit is to review data from Flash-glucose monitoring and finger-stick glucose monitoring to further optimise treatment. Study devices will be downloaded. Information about insulin doses and any adverse events will be collected.
Visit 5: (+12 weeks since randomisation): Review data and treatment optimisation
Purpose of this visit is to review data from Flash-glucose monitoring and finger-stick glucose monitoring to further optimise treatment. Study devices will be downloaded. Information about insulin doses, participant diaries and any adverse events will be collected. A blood sample will be collected for HbA1c.
Visit 6: (+22 weeks since randomisation): Finger-stick glucose monitoring arm only
Participants randomised to finger-stick glucose monitoring arm will have an extra visit ten weeks after visit 5 to insert a blinded glucose sensor for data capture.
Visit 7: (+24 weeks since randomisation): End of randomised study treatment
The participant will be invited to attend the research centre approximately 12 weeks after Visit 5. This would be the end of 24 weeks randomised study period. All study devices will be downloaded. Insulin usage data will be recorded and diaries collected. The participant will have a blood test for the HbA1c. Body weight measurement will be made. The participant will be asked to complete the same questionnaires completed at Visit 1. In addition, participants in the FSL2 arm will be asked to complete a additional questionnaire exploring expectations and experience of using FSL2 during the study. A subset of participants (n=40 aiming for 25 completed questionnaires) in the FSL2 arm and subset of researchers (n=10) will also be asked to complete additional questionnaires to help with the process evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Free Style Libre 2 device | Experimental | Device: Free Style Libre 2At the start, a blood sample will be taken for the measurement of HbA1c. Training and education on the use of FSL2 will be provided by the research team. Participants will be advised to use flash glucose monitoring continuously for the next 24 weeks. |
| Self-monitoring of blood glucose | No intervention | –At the start, a blood sample will be taken for the measurement of HbA1c. Masked FSL will be applied for two weeks, during the last two weeks of control period. Education will focus on using fingerstick measurement for treatment optimisation. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- The participant is ≥16 years old
- The participant has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative if duration of diabetes is < 1 years
- Participant is treated with insulin pump or multiple daily injection for at least 12 weeks and no plans to change treatment modality during next 28 weeks
- The participant is literate in English for safe study conduct
- Screening HbA1c ≥ 7.5% (58.5mmol/mol) and ≤ 11% (97 mmol/mol) based on analysis from local laboratory
Key exclusion criteria (9 listed)
- Non-type 1 diabetes mellitus including those secondary to chronic disease
- Any other physical disease or people with known severe mental illness (psychotic disorder, bipolar disorder, dementia, substance and alcohol dependence, learning disabilities, depression with active suicidal ideation) which are likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- Current users of real-time glucose monitoring sensors or flash-glucose monitoring for more than 4 weeks within last 12 weeks
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, SGLT2 inhibitors, GLP-1 agonists, Pramlinatide, non-selective beta-blockers and MAO inhibitors etc.(patients on stable metformin is not an exclusion)
- Known or suspected allergy against insulin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Free Style Libre 2FreeStyle Libre 2 (FSL2) is a novel glucose monitoring device (Flash glucose monitoring) in the form of a disc worn on the arm for 14 days and a hand-held reader which is designed to largely replace the recommended 4-10 painful finger-stick blood glucose tests required each day for the self-management of type 1 diabetes (T1D). | Device | Free Style Libre 2 device |
Primary outcome
HbA1c Level at 24 Weeks
Time frame: 24 weeks
The primary outcome is difference in HbA1c between the two groups at 24 weeks.
30 secondary outcomes
HbA1c Level at 12 Weeks
Time frame: 12 weeks
Percentage With HbA1c ≤ 53 mmol/Mol (7.0%) at 12 Weeks
Time frame: 12 weeks
Percentage With HbA1c ≤ 53 mmol/Mol (7.0%) at 24 Weeks
Time frame: 24 weeks
Sensor Based - Time Spent in the Target Glucose Range Between 3.9 to 10.0 mmol/l
Time frame: 24 weeks
Sensor Based - Time Spent Below Target Glucose (<3.9mmol/l)
Time frame: 24 weeks
Sensor Based - Time Spent Above Target Glucose (10.0 mmol/l)
Time frame: 24 weeks
Sensor Based - Average Glucose Levels
Time frame: 24 weeks
Sensor Based - Standard Deviation Glucose Levels
Time frame: 24 weeks
Sensor Based - Coefficient of Variation Glucose Levels
Time frame: 24 weeks
Sensor Based - Time With Sensor Glucose Levels < 3.5 mmol/l
Time frame: 24 weeks
Sensor Based - Time With Sensor Glucose Levels < 3.5 mmol/l
Time frame: 24 weeks
Sensor Based - Time With Sensor Glucose Levels < 2.8 mmol/l
Time frame: 24 weeks
Sensor Based - Time With Sensor Glucose Levels in the Significant Hyperglycaemia
Time frame: 24 weeks
Sensor Based - AUC of Glucose Below 3.0mmol/l
Time frame: 24 weeks
Total Daily Average Insulin Dose
Time frame: 24 weeks
Daily Average Basal Insulin Dose
Time frame: 24 weeks
Daily Average Bolus Dose
Time frame: 24 weeks
Average Number of Boluses of Rapid Acting Insulin
Time frame: 24 weeks
Number of Freestyle Libre Scans Per Day
Time frame: 24 weeks
Frequency of Severe Hypoglycaemic Episodes
Time frame: 24 weeks
Frequency of Significant Ketosis Events
Time frame: 24 weeks
Nature and Severity of Other Adverse Events
Time frame: 24 weeks
Type 1 Diabetes Distress Scale Score
Time frame: 24 weeks
EQ-5D-5L Quality of Life Questionnaire Score
Time frame: 24 weeks
Patient Health Questionnaire Score
Time frame: 24 weeks
Diabetes Fear of Injecting and Self-Testing Questionnaire Score
Time frame: 24 weeks
The Revised Diabetes Eating Problem Survey Score
Time frame: 24 weeks
Average Number of Days of Libre Usage Per Week
Time frame: 24 weeks
Diabetes Treatment Satisfaction Questionnaire Score
Time frame: 24 weeks
Glucose Monitoring Satisfaction Survey Score
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29356072Leelarathna L, Wilmot EG. Flash forward: a review of flash glucose monitoring. Diabet Med. 2018 Apr;35(4):472-482. doi: 10.1111/dme.13584. Epub 2018 Feb 27.
- Derived from this study: PubMed 36198143Leelarathna L, Evans ML, Neupane S, Rayman G, Lumley S, Cranston I, Narendran P, Barnard-Kelly K, Sutton CJ, Elliott RA, Taxiarchi VP, Gkountouras G, Burns M, Mubita W, Kanumilli N, Camm M, Thabit H, Wilmot EG; FLASH-UK Trial Study Group. Intermittently Scanned Continuous Glucose Monitoring for Type 1 Diabetes. N Engl J Med. 2022 Oct 20;387(16):1477-1487. doi: 10.1056/NEJMoa2205650. Epub 2022 Oct 5.
- Derived from this study: PubMed 34261691Wilmot EG, Evans M, Barnard-Kelly K, Burns M, Cranston I, Elliott RA, Gkountouras G, Kanumilli N, Krishan A, Kotonya C, Lumley S, Narendran P, Neupane S, Rayman G, Sutton C, Taxiarchi VP, Thabit H, Leelarathna L. Flash glucose monitoring with the FreeStyle Libre 2 compared with self-monitoring of blood glucose in suboptimally controlled type 1 diabetes: the FLASH-UK randomised controlled trial protocol. BMJ Open. 2021 Jul 14;11(7):e050713. doi: 10.1136/bmjopen-2021-050713.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the primary study manuscript after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Free Style Libre 2 in people with Diabetes Mellitus, Type 1, run by Manchester University NHS Foundation Trust at 8 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HbA1c Level at 24 Weeks (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03815006, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2023.