Assessment of the Impact of Real-Time Continuous Glucose Monitoring on People Presenting With Severe Hypoglycaemia (AIR-CGM)

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.

Study Overview

• Status: Terminated
• Conditions: Hypoglycemia; Diabetes Mellitus, Type 1; Hypoglycemia Unawareness
• Intervention / Treatment: Device: Dexcom G6 CGM; Device: Tandem t:slim X2 Insulin Pump

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Imperial College Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous Glucose Monitoring (CGM); The RT CGM group will receive a Dexcom G6 transmitter and sensors, as well as a structured education refresher focusing on hypoglycaemia avoidance, recognition, and management.	Device: Dexcom G6 CGM; Commercially available Dexcom G6 Continuous Glucose Monitoring
No Intervention: Self Monitoring Blood Glucose (SMBG); The SMBG group will additionally undergo blinded CGM at weeks 1 and 2, weeks 4 to 6 and weeks 9 to 12 using the Dexcom G6 system. Participants in this group will be shown how to insert the Dexcom G6 at the first clinic visit and sensors provided so they can do this at home.
Experimental: Continuous Subcutaneous Insulin Infusion (CSII); All participants will be re-consented with the choice to continue using RT-CGM for a further 16 weeks or be re-randomised to either receive the Tandem t:slim X2 insulin pump or RT-CGM. Participants randomised to the Tandem t:slim X2 group will be proficiently trained to safely use the Tandem t:slim X2 insulin pump. All participants (Tandem t:slim X2 and RT-CGM) will be provided with Dexcom G6 real time CGM transmitters and sensors for the 16-week second extension phase.	Device: Dexcom G6 CGM; Commercially available Dexcom G6 Continuous Glucose Monitoring; Device: Tandem t:slim X2 Insulin Pump; sensor augmented insulin pump with predictive low glucose suspend

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Spent in Hypoglycaemia	Percentage time spent in hypoglycaemia (<3.0mmol/L, 55mg/dL)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent in hypoglycaemia (<3.9mmol/L, 70mg/dL)	Percentage time spent in hypoglycaemia (<3.9mmol/L, 70mg/dL)	12 weeks
Number of episode of serious hypoglycaemia	defined as a sensor glucose <3.0mmol/L (55mg/dL) for >20 minutes	12 weeks
time in euglycaemia	% time in euglycaemia (3.9-7.8mmol/L, 70-140mg/dL)	12 weeks
time spent in target	% time spent in target (3.9-10mmol/L, 70-180mg/dL)	12 weeks
time spent in hyperglycaemia	% time spent in hyperglycaemia (>10mmol/L, 180mg/dL)	12 weeks
hypoglycaemic excursions	Number hypoglycaemic excursions	12 weeks
Severe Hypoglycaemia	Measured via CGM	12 weeks
Mean Absolute Difference in Glucose (MAD%)	Measured via CGM expressed as a percentage reference value	12 weeks
Glucose Variability	Measured via CGM	12 weeks
HbA1C	Measured via venous blood tests	12 weeks
Ambulance call-out rates	Provided by LAS	12 weeks
DTSQ	Diabetes Treatment Satisfaction Questionnaire	12 weeks
CGM Usability	Continuous Glucose Monitoring Usability Questionnaire	12 weeks
PAID	Problem Area in Diabetes Questionnaire	12 weeks
Gold Score	Hypoglycaemia awareness (GOLD score) questionnaire	12 weeks
HFS2 questionnaire	Fear of Hypoglycaemia Survey Score	12 weeks
Cost effectiveness (measured in pounds sterling)	Cost effectiveness of CGM when compared with SMBG	12 weeks

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: London Ambulance Service
• Investigators: Principal Investigator: Nick Oliver, Imperial College London

Publications and helpful links

General Publications

• 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.

Helpful Links

• NICE Guidelines

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): September 9, 2021
• Study Completion (Actual): September 9, 2021

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: continuous subcutaneous insulin infusion; Real time continuous glucose monitoring; self monitoring blood glucose; sensor augmented pump; severe hypoglycaemia; hypounaware
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 18HH4609

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No