Clinical trial NCT03748433: Assessment of the Impact of Real-Time Continuous Glucose Monitoring on People Presenting With Severe Hypoglycaemia
Official title: Assessment of the Impact of Real-Time Continuous Glucose Monitoring on People Presenting With Severe Hypoglycaemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Hypoglycemia Unawareness
Hypoglycemia
Keywords: Real time continuous glucose monitoring
continuous subcutaneous insulin infusion
self monitoring blood glucose
sensor augmented pump
severe hypoglycaemia
hypounaware
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: London Ambulance Service
First posted: 2018-11-20
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised open-label parallel group study
Primary purpose: TREATMENT

Brief summary: This study aims to assess the impact of real-time continuous glucose monitoring on the frequency, duration, awareness and severity of hypoglycaemia in people with type 1 diabetes and a recent history of severe hypoglycaemia, compared to usual care.

Detailed description: Type 1 diabetes (T1DM), which affects 300,000 in the UK, is characterised by autoimmune destruction of the pancreatic beta cells, leading to absolute deficiency of insulin. Management of T1DM requires exogenous insulin administration, aiming for glucose concentrations as close to physiological values as possible. Intensive management of T1DM improves glucose control and reduces the risk of microvascular diabetes complications and cardiovascular disease1. In the UK diabetes consumes more than 10% of the National Health Service budget 2 and in the USA a relatively greater amount is spent on type 1 compared with type 2 diabetes (8.6% of the diabetes budget compared with 5.6% of diabetes prevalence)3. Medication and insulin pump therapy accounts for less than 10% of diabetes expenditure with the majority of costs incurred in the treatment of complications4.

Optimal control remains challenging to achieve and intensive insulin treatment increases the risk of severe hypoglycaemia, with lower glucose values also associated with an increased frequency and severity of moderate hypoglycaemia5, 6. Severe hypoglycaemia is defined as any episode of hypoglycaemia requiring the assistance of a third party actively to treat. Hypoglycaemia is associated with morbidity and even mortality, and places a financial burden on health systems.

Severe hypoglycaemia costs £13million per year in NHS costs7. Between 4 and 10% of deaths in people with type 1 diabetes are attributed to hypoglycaemia and the risk of severe hypoglycaemia increases 6-fold in people with impaired awareness of hypoglycaemia. Avoidance of hypoglycaemia is associated with restoration of hypoglycaemia awareness and this may be enabled by the use of continuous glucose monitoring.

In type 1 diabetes real-time continuous glucose monitoring (CGM) improves overall glucose control in all age groups when used continuously, reduces hypoglycaemia in people with an HbA1c \<7.0%, and may reduce severe hypoglycaemia8-10.

The predictive Low-Glucose suspend (PLGS) feature in sensor augmented insulin pumps (SAP) automatically reduces insulin delivery when trends in CGM glucose concentrations predict future hypoglycaemia, and significantly reduces hypoglycaemia without rebound hyperglycaemia compared to SAP without PLGS11.

In England continuous glucose monitoring is supported by NICE for people with type 1 diabetes who are willing to commit to using it at least 70% of the time and to calibrate it as needed, and who have any of the following despite optimised use of insulin therapy and conventional blood glucose monitoring12:

* More than 1 episode a year of severe hypoglycaemia with no obvious preventable precipitating cause.
* Complete loss of awareness of hypoglycaemia.
* Frequent (more than 2 episodes a week) asymptomatic hypoglycaemia that is causing problems with daily activities.
* Extreme fear of hypoglycaemia.
* Hyperglycaemia (HbA1c level of 75 mmol/mol \[9%\] or higher) that persists despite testing at least 10 times a day

Addressing severe hypoglycaemia, reducing the risk of further episodes and acting promptly to optimise hypoglycaemia awareness are critical in people at high risk.

Continuous subcutaneous insulin pump therapy is supported for adults and children over 12 with type 1 diabetes in whom attempts to achieve target haemoglobin A1c (HbA1c) with multiple daily injections (MDI) have resulted in disabling hypoglycaemia or HbA1c levels have remained high (8.5% \[69 mmol/mol\] or above) despite high level care12.

Eligibility criteria: PRE-REGISTRATION EVALUATIONS

* Episode of severe hypoglycaemia
* Age \>18 years
* Diagnosis of type 1 diabetes

INCLUSION CRITERIA

* Adults over 18 years of age
* Severe hypoglycaemia requiring ambulance call-out or emergency department attendance within 2 weeks
* Type 1 diabetes confirmed on the basis of clinical features
* Type 1 diabetes for greater than 3 years

EXCLUSION CRITERIA

* Use of CGM within the last 6 months (except short periods of diagnostic blinded use under clinic supervision). Prior use of Abbott FreeStyle Libre Device is permitted.
* Use of pre-mixed insulin
* No access to smartphone or computer
* Pregnant or planning pregnancy
* Breastfeeding
* Have active malignancy or under investigation for malignancy
* Severe visual impairment
* Reduced manual dexterity
* Unable to participate due to other factors, as assessed by the Chief Investigators

WITHDRAWAL CRITERIA

Participants will be withdrawn if their ability to give informed consent is impaired. Participants will also be withdrawn, at the chief investigators discretion, if glucose control is negatively impacted by the use of either intervention.

Primary outcomes:
measure: Time Spent in Hypoglycaemia
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Clinical Research Facility
Study officials:
affiliation: Imperial College London
name: Nick Oliver
role: PRINCIPAL_INVESTIGATOR
References:
citation: Avari P, Ramli R, Reddy M, Oliver N, Fothergill R. Rationale and protocol for the Assessment of Impact of Real-time Continuous Glucose Monitoring on people presenting with severe Hypoglycaemia (AIR-CGM) study. BMC Endocr Disord. 2019 Oct 26;19(1):110. doi: 10.1186/s12902-019-0439-3.