Impaired Awareness of Hypoglycemia, Type1diabetes, Type 1 Diabetes Mellitus With Hypoglycemia
Conditions
Keywords
Type 1 Diabetes, Hypoglycemia
Brief summary
This clinical study proposes to assess the impact of Libre on frequency, duration and severity of hypoglycaemia, compared with the Dexcom G5 realtime CGM and will focus on people with impaired awareness of hypoglycaemia.
Detailed description
Good glucose control in type 1 diabetes is associated with a reduced risk of diabetes complications and self monitoring of glucose levels is an important component of achieving and maintaining glucose control. Continuous glucose monitoring (CGM) improves overall glucose control in all age groups when used continuously, and reduces the incidence of low blood glucose (hypoglycaemia) in people with good glucose control. Hypoglycaemia is one of the commonest metabolic complications of type 1 diabetes and, if it occurs frequently, people can become less aware of it. This reduced aware of hypoglycaemia has significant risks including seizures, coma and even death, and has an impact on people's ability to drive and function. The Abbott Libre intermittent glucose monitoring system provides up to 8 hours of retrospective continuous glucose monitoring data to users when the monitor is waved in proximity with the sensor. In contrast to realtime CGM the Libre system sensor is used for 14 days and is non-adjunctive (does not require calibration to capillary blood glucose).
Interventions
DEVICEDexcom G5 Continuous Glucose Monitor
Real time continuous glucose sensor connected to monitor providing data and alarms and alerts for glucose trends and values
DEVICEAbbott Freestyle Libre
Continuous glucose recording device which reports glucose concentration and trend on demand, along with a retrospective review of the last 8 hours glucose data
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults over 18 years of age * Type 1 diabetes confirmed on the basis of clinical features and a fasting c-peptide \<200 pmol/L * Severe hypoglycaemic event in the last 12 months requiring third party assistance OR a Gold Score ≥ 4 * Type 1 diabetes for greater than 3 years * On an intensified multiple dose insulin injection regimen for \> 6 months (MDI) * Previous type 1 diabetes structured education (either group or 1:1)
Exclusion criteria
* Use of CGM or Libre device within the last 6 months (except short periods of diagnostic blinded use under clinic supervision) * Use of regular paracetamol * Pregnant or planning pregnancy * Breastfeeding * Enrolled in other clinical trials, except at the discretion of the chief investigator * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| % Time Spent in Hypoglycaemia (<3.3mmol/L, 60mg/dL) | 10 weeks | Percentage time spent in hypoglycaemia (\<3.3mmol/L, 60mg/dL) change from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Time Spent in Hypoglycaemia (<3.9mmol/L, 70mg/dL) | 10 weeks | Percentage time spent in hypoglycaemia (\<3.9mmol/L, 70mg/dL) change in baseline to endpint |
| % Time Spent in Euglycaemia (3.9-7.8mmol/L, 70-140mg/dL) | 10 weeks | Percentage time spent in euglycaemia (3.9-7.8mmol/L, 70-140mg/dL) change in baseline to endpoint |
| % Time Spent in Euglycaemia (3.9-10mmol/L, 70-180mg/dL) | 10 weeks | Percentage time spent in euglycaemia (3.9-10mmol/L, 70-180mg/dL) change in baseline to endpoint |
| % Time Spent in Hyperglycaemia (>10mmol/L, 180mg/dL) | 10 weeks | Percentage time spent in hyperglycaemia (\>10mmol/L, 180mg/dL) change in baseline to endpoint |
| % Time Spent in Hyperglycaemia (>15mmol/L, 270mg/dL) | 10 weeks | % time spent in hyperglycaemia (\>15mmol/L, 270mg/dL) change in baseline to endpoint |
| % Time Spent in Hypoglycaemia (<2.8mmol/L, 50mg/dL) | 10 weeks | Percentage time spent in hypoglycaemia (\<2.8mmol/L, 50mg/dL) change from baseline |
| Severe Hypoglycaemia | 8 weeks | Number of participants with episodes of severe hypoglycaemia |
| Changes in Glucose Variability Measured | 8 weeks | Glucose Variability measured by Coefficient of variation (CV), on a decimal scale of 0-1 |
| Glucose Variability Measured by MAGE | 8 weeks | Glucose Variability measured by Mean amplitude of Glycaemic Excursions (MAGE) |
| Glucose Variability Measured by CONGA | 8 weeks | Glucose Variability measured by Continuous Overlapping Net Glycaemic Action (CONGA) |
| Hypoglycemia | 8 weeks | Number of participants with hypoglycemic excursions |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Real Time Continuous Glucose Monitoring Use of Dexcom G5 continuous glucose monitoring
Dexcom G5 Continuous Glucose Monitor: Real time continuous glucose sensor connected to monitor providing data and alarms and alerts for glucose trends and values | 20 |
| Flash Glucose Monitoring Use of Abbott FreeStyle Libre flash glucose monitoring
Abbott Freestyle Libre: Continuous glucose recording device which reports glucose concentration and trend on demand, along with a retrospective review of the last 8 hours glucose data | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Flash Glucose Monitoring | Total | Real Time Continuous Glucose Monitoring |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 40 Participants | 20 Participants |
| Age, Continuous | 48.5 years | 49.5 years | 50.5 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 12 Participants | 24 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
% Time Spent in Hypoglycaemia (<3.3mmol/L, 60mg/dL)
Percentage time spent in hypoglycaemia (\<3.3mmol/L, 60mg/dL) change from baseline
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Hypoglycaemia (<3.3mmol/L, 60mg/dL) | -3.0 percentage of time <3.3mmol/l |
| Flash Glucose Monitoring | % Time Spent in Hypoglycaemia (<3.3mmol/L, 60mg/dL) | 1.3 percentage of time <3.3mmol/l |
p-value: 0.01Wilcoxon (Mann-Whitney)
Secondary
Changes in Glucose Variability Measured
Glucose Variability measured by Coefficient of variation (CV), on a decimal scale of 0-1
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | Changes in Glucose Variability Measured | -0.1 percent |
| Flash Glucose Monitoring | Changes in Glucose Variability Measured | 0.0 percent |
p-value: 0.91Wilcoxon (Mann-Whitney)
Secondary
Glucose Variability Measured by CONGA
Glucose Variability measured by Continuous Overlapping Net Glycaemic Action (CONGA)
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | Glucose Variability Measured by CONGA | 0.1 mmol/l |
| Flash Glucose Monitoring | Glucose Variability Measured by CONGA | 0.1 mmol/l |
p-value: 0.191Wilcoxon (Mann-Whitney)
Secondary
Glucose Variability Measured by MAGE
Glucose Variability measured by Mean amplitude of Glycaemic Excursions (MAGE)
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | Glucose Variability Measured by MAGE | -1.5 mmol/L |
| Flash Glucose Monitoring | Glucose Variability Measured by MAGE | -0.4 mmol/L |
p-value: 0.46Wilcoxon (Mann-Whitney)
Secondary
Hypoglycemia
Number of participants with hypoglycemic excursions
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | Hypoglycemia | 0 Participants |
| Flash Glucose Monitoring | Hypoglycemia | 0 Participants |
p-value: 0.57Wilcoxon (Mann-Whitney)
Secondary
Severe Hypoglycaemia
Number of participants with episodes of severe hypoglycaemia
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | Severe Hypoglycaemia | 0 Participants |
| Flash Glucose Monitoring | Severe Hypoglycaemia | 0 Participants |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
% Time Spent in Euglycaemia (3.9-10mmol/L, 70-180mg/dL)
Percentage time spent in euglycaemia (3.9-10mmol/L, 70-180mg/dL) change in baseline to endpoint
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Euglycaemia (3.9-10mmol/L, 70-180mg/dL) | 12.7 percentage of time >3.9<10 mmol/l |
| Flash Glucose Monitoring | % Time Spent in Euglycaemia (3.9-10mmol/L, 70-180mg/dL) | 5.3 percentage of time >3.9<10 mmol/l |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
% Time Spent in Euglycaemia (3.9-7.8mmol/L, 70-140mg/dL)
Percentage time spent in euglycaemia (3.9-7.8mmol/L, 70-140mg/dL) change in baseline to endpoint
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Euglycaemia (3.9-7.8mmol/L, 70-140mg/dL) | 10.6 percentage of time >3.9<7.8 mmol/l |
| Flash Glucose Monitoring | % Time Spent in Euglycaemia (3.9-7.8mmol/L, 70-140mg/dL) | 5.9 percentage of time >3.9<7.8 mmol/l |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
% Time Spent in Hyperglycaemia (>10mmol/L, 180mg/dL)
Percentage time spent in hyperglycaemia (\>10mmol/L, 180mg/dL) change in baseline to endpoint
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Hyperglycaemia (>10mmol/L, 180mg/dL) | -8.6 percentage of time >10mmol/L |
| Flash Glucose Monitoring | % Time Spent in Hyperglycaemia (>10mmol/L, 180mg/dL) | -7.0 percentage of time >10mmol/L |
p-value: 0.82Wilcoxon (Mann-Whitney)
Secondary
% Time Spent in Hyperglycaemia (>15mmol/L, 270mg/dL)
% time spent in hyperglycaemia (\>15mmol/L, 270mg/dL) change in baseline to endpoint
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Hyperglycaemia (>15mmol/L, 270mg/dL) | -4.9 percentage of time >15 mmol/l |
| Flash Glucose Monitoring | % Time Spent in Hyperglycaemia (>15mmol/L, 270mg/dL) | -3.1 percentage of time >15 mmol/l |
p-value: 0.82Wilcoxon (Mann-Whitney)
Secondary
% Time Spent in Hypoglycaemia (<2.8mmol/L, 50mg/dL)
Percentage time spent in hypoglycaemia (\<2.8mmol/L, 50mg/dL) change from baseline
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Hypoglycaemia (<2.8mmol/L, 50mg/dL) | -1.2 percentage of time <2.8mmol/l |
| Flash Glucose Monitoring | % Time Spent in Hypoglycaemia (<2.8mmol/L, 50mg/dL) | 1.3 percentage of time <2.8mmol/l |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
% Time Spent in Hypoglycaemia (<3.9mmol/L, 70mg/dL)
Percentage time spent in hypoglycaemia (\<3.9mmol/L, 70mg/dL) change in baseline to endpint
Time frame: 10 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Real Time Continuous Glucose Monitoring | % Time Spent in Hypoglycaemia (<3.9mmol/L, 70mg/dL) | -2.7 percentage of time <3.9mmol/l |
| Flash Glucose Monitoring | % Time Spent in Hypoglycaemia (<3.9mmol/L, 70mg/dL) | 0.6 percentage of time <3.9mmol/l |
p-value: <0.01Wilcoxon (Mann-Whitney)