Clinical trial NCT04304963: Hypo-METRICS: Hypoglycaemia - Measurement, ThResholds and ImpaCtS
Official title: Hypo-METRICS: Hypoglycaemia - Measurement, ThResholds and ImpaCtS A Clinical Study to Determine the Optimal Threshold and Duration of Low Interstitial Glucose Events That Have an Impact on Patient Experienced Hypoglycaemia, Quality of Life and Health Economic Outcomes.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Hypoglycemia
Hypoglycemia Unawareness
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: University of Southern Denmark
name: Sheffield Teaching Hospitals NHS Foundation Trust
name: Cambridge University Hospitals NHS Foundation Trust
name: Ninewells Hospital
name: Radboud University Medical Center
name: Nordsjaellands Hospital
name: Medical University of Graz
name: University Hospital, Montpellier
name: Innovative Medicines Initiative
name: The Leona M. and Harry B. Helmsley Charitable Trust
name: Juvenile Diabetes Research Foundation
name: International Diabetes Federation
name: Novo Nordisk A/S
name: Abbott Diabetes Care
name: Medtronic Diabetes
First posted: 2020-03-12
Enrollment: 602
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total of 600 participants will be recruited in the following categories.

* Type 1 diabetes with intact awareness of hypoglycaemia \[ Gold score \< 3\]; a maximum of 50% will be using flash or continuous glucose monitoring \[ n = 200 \]
* Type 1 diabetes with impaired awareness of hypoglycaemia \[ gold score \> 4 \];\[n=50\] a maximum of 50% will be using flash or continuous glucose monitoring
* Type 2 diabetes on \> 1 injections; a minimum of 25% of these participants will be over 60 years of age; a maximum of 50% will be using flash or continuous glucose monitoring. \[n=350\]

Brief summary: Hypoglycaemia or low blood glucose, and its fear are major barriers to achieving optimal glucose control. New technology, such as continuous glucose monitors (CGM), help to better identify hypoglycaemia and develop strategies to avoid it. These devices measure glucose in the skin, rather than in the blood, and provide information not only on how low glucose is, but also for how long. Recent studies showed that over half of episodes of low glucose with these systems are not recognised by people with diabetes, and even people without diabetes have sensor values that are below the current thresholds for hypoglycaemia \[ low blood glucose\] that we measure with traditional monitors.

In this study, the investigators will evaluate the impact of symptomatic as well as asymptomatic episodes of low sensor glucose on a variety of clinical, patient-related and health economic outcomes such as mood, quality of sleep and productivity. The investigators will test different levels and durations of low sensor glucose to identify the one that best matches episodes that are symptomatic to best define hypoglycaemia using these systems.

The investigators will also look at factors that influence this such as sleep or activity as well as diabetes management behaviours (such as insulin dosing, carb counting, etc). At the end of this study, the investigators will be able to provide a better definition of clinically relevant low sensor glucose readings that will help inform clinical as well as academic interpretation of CGM data.


Eligibility criteria: Inclusion Criteria:

1. Age 18 - 85 years
2. HbA1c 5 - 10% \[31 - 86 mmol/mol\]
3. Confirmed diagnosis of type 1 or type 2 diabetes
4. Using \> 1 injection of insulin / day or insulin pump.
5. Ability to provide written informed consent
6. Performing regular SMBG \[ \> 1 / day on a 4-week download\] . For those using flash or continuous glucose monitoring, this should be used at least 70% of the time.
7. At least 1 episode of hypoglycaemia \[ either biochemical or symptomatic\] in the last month
8. On stable therapy for at least 3 months.
9. Willing to complete study procedures including wearing the Fitbit and CGM devices and completing the EMA questionnaires on the uMotif app three times a day for 10 weeks ( we expect minimum 80% data completeness)

Exclusion Criteria:

1. Concurrent conditions that can affect glucose readings \[renal impairment GFR \< 30 ml/min, hepatic impairment, untreated adrenal or thyroid insufficiency, as judged by the investigator.
2. Severe cognitive impairment or psychological illness that can impair performance of EMA tasks, visual impairment that will preclude use of the EMA or sensors.
3. Severe psychiatric / psychological illness including extreme fear of hypo- or hyper- glycaemia ( in the opinion of the investigator)
4. Pregnant or plans for pregnancy in the next 6 months
5. Use of automated insulin delivery systems such as closed loop or automated threshold suspend or predictive low glucose suspend insulin pumps.
6. Known allergies to adhesives required for the CGM systems
7. People who work regular night shifts
8. Any other condition which in the opinion of the study team would impair their ability to complete the study

Primary outcomes:
measure: LIG optimum detection of hypoglycemia
timeFrame: week 10
Secondary outcomes:
measure: Secondary outcome 1
timeFrame: week 10
measure: Secondary outcome 2
timeFrame: week 10
measure: Secondary outcome 3
timeFrame: week 10
measure: Secondary outcome 4
timeFrame: week 10
measure: Secondary outcome 5
timeFrame: week 10
measure: Secondary outcome 6
timeFrame: week 10
measure: Secondary outcome 7
timeFrame: week 10
measure: Secondary outcome 8
timeFrame: week 10
measure: Secondary outcome 9
timeFrame: week 10
measure: Secondary outcome 10
timeFrame: week 10
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College London
Study officials:
References:
citation: Divilly P, Zaremba N, Mahmoudi Z, Soholm U, Pollard DJ, Broadley M, Abbink EJ, de Galan B, Pedersen-Bjergaard U, Renard E, Evans M, Speight J, Brennan A, McCrimmon RJ, Mullenborn M, Heller S, Seibold A, Mader JK, Amiel SA, Pouwer F, Choudhary P; Hypo-RESOLVE Consortium. Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol. Diabet Med. 2022 Sep;39(9):e14892. doi: 10.1111/dme.14892. Epub 2022 Jun 22.
citation: Soholm U, Broadley M, Zaremba N, Divilly P, Nefs G, Mahmoudi Z, de Galan B, Pedersen-Bjergaard U, Brennan A, Pollard DJ, McCrimmon RJ, A Amiel S, Hendrieckx C, Speight J, Choudhary P, Pouwer F; Hypo-RESOLVE Consortium. Investigating the day-to-day impact of hypoglycaemia in adults with type 1 or type 2 diabetes: design and validation protocol of the Hypo-METRICS application. BMJ Open. 2022 Feb 1;12(2):e051651. doi: 10.1136/bmjopen-2021-051651.