Assessment of the Accuracy of Continuous Glucose Sensors in People With Diabetes Undergoing Haemodialysis

Study Overview
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Brief Summary
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The purpose of the study is to assess the accuracy of the Dexcom G6 CGM system and the Abbott FreeStyle Libre flash system compared to the reference standard YSI (Yellow Spring Instruments) glucose in people with diabetes undergoing haemodialysis. The Dexcom G6 is a continuous glucose monitoring system that gives blood glucose values in real-time and includes alarms if the glucose is very low or high. The Abbott FreeStyle ibre flash system is an intermittent glucose monitor that shows the blood glucose values when it is waved near the sensor and does not include alarms. The YSI glucose analysis will take place as a normal part of haemodialysis, by testing blood glucose levels during the haemodialysis session. The study will last 28 days per participant

Detailed Description
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Diabetic nephropathy is the leading cause of end-stage renal failure (ESRF), representing approximately 40% of people requiring long-term renal replacement therapy and maintenance haemodialysis [1]. Mortality and morbidity within this cohort is high, with the predominant cause being cardiovascular disease (CVD) [2]. Glycaemic control in many haemodialysis dependent patients with diabetes is poor and may lead to additional renal complications, including high interdialytic weight gain, electrolyte imbalance, and amputations [3]. Current clinical guidance is centred around the prevention of hyperglycaemia and microvascular complications of diabetes. Glucose self-management is particularly challenging due to cyclical changes in insulin sensitivity and circulating insulin concentrations. Hypoglycemia is common due to impaired renal gluconeogenesis, malnutrition, and the increased half-life of insulin and hypoglycemic agents [4, 5]. Additionally, people with chronic kidney disease and diabetes may have other diabetes complications such as retinopathy, neuropathy, and impaired awareness of hypoglycaemia, which can make self-management more difficult. Overall assessment of glycaemic control is also more complex as classical markers of glycemic control (i.e. HbA1c and fructosamine) may be misleading due to the variable underestimation of glycaemia resulting from analytical interferences, shortened half-life of red blood cells and abnormal albumin level [6-8]. Further limitations of HbA1c is that it is not informative regarding glycemic control on the days on and off dialysis, and intra-day glycaemic variability. Frequent capillary blood glucose tests or self-monitoring of blood glucose (SMBG) is the traditional and one of the most effective ways to track an individuals' blood glucose levels. Real-time continuous glucose monitoring (CGM) has been shown to improve overall glucose control, reduce hypoglycaemia in people with an HbA1c <7.0%, and may reduce severe hypoglycaemia [9-11]. In addition, they provide alert and alarm features for hypo- and hyperglycaemia, and for times of rapid glucose change. Flash glucose monitoring does not provide real-time data with alerts and alarms, but allows users to retrospectively review the preceding 8 hours of continuous glucose data, along with a contemporary estimated blood glucose value and trend line. The system consists of a subcutaneous sensor placed on the back of the upper arm, which measures glucose in the interstitial fluid every minute. The glucose data are made available when the user chooses to swipe the reader over the sensor. CGM has the potential to reduce HbA1c and minimize exposure to hypoglycaemia while addressing diabetes distress. Flash glucose monitoring may reduce exposure to hypoglycaemia in people with insulin-treated diabetes. The accuracy of CGM and flash in people with diabetes on haemodialysis has not been described. In this clinical study, the investigators will assess the accuracy of the Dexcom G6 CGM system and the Abbott FreeStyle Libre flash system compared to YSI (Yellow Spring Instruments) glucose in people undergoing haemodialysis.

Official Title
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Assessment of the Accuracy of Continuous Glucose Sensors in People With Diabetes Undergoing Haemodialysis

Conditions
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Diabetic Nephropathies, Type 1 Diabetes Mellitus, Chronic Kidney Diseases

Intervention / Treatment
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* Device: Dexcom G6 and Abbott Freestyle Libre


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults >18 years of age Diabetes, with insulin treatment for over 6 months or on sulphonylureas Chronic kidney disease requiring haemodialysis three times per week Exclusion Criteria: Pregnant or planning pregnancy Breastfeeding Enrolled in other clinical trials 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexcom G6 and Abbott Freestyle Libre<br>Participants will have a Dexcom G6 sensor and Abbott FreeStyle Libre sensor inserted in the abdomen and upper arm respectively. Participants will be asked to swipe the FreeStyle Libre reader across the sensor a minimum of every 8 hours. Participants will be asked to continue their usual regimen of self-monitoring capillary blood glucose (SMBG). During haemodialysis, a dialysis circuit blood sample will be drawn at 0 (pre-dialysis) 30, 60, 90, 120, 150, 180, 210 and 240 minutes and immediately after dialysis. Samples from the circuit will be analysed on the YSI glucose analyser. Participants will be asked to change the FreeStyle Libre sensors at day 14. The blinded CGM data will be uploaded at the time of each sensor change by the research team. | Device: Dexcom G6 and Abbott Freestyle Libre<br>* Dexcom G6 - continuous glucose monitoring device - blinded. CE mark 2018 Abbott Freestyle Libre - flash glucose monitoring device. CE mark 2014<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MARD between G6 and YSI | Mean absolute relative difference between Dexcom G6 and YSI glucose during haemodialysis | 28 days | 
| MARD between Libre and YSI | Mean absolute relative difference between Dexcom G6 and YSI glucose during haemodialysis | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | Glycated Haemoglobin | 28 days | 
| MARD for G6 and YSI <3.9mmol/L | Mean absolute relative difference between Dexcom G6 and YSI glucose <3.9mmol/L | 28 days | 
| MARD for Libre and YSI <3.9mmol/L | Mean absolute relative difference between Libre and YSI glucose <3.9mmol/L | 28 days | 
| MARD for Libre and YSI 3.9-10mmol/L | Mean absolute relative difference between Libre and YSI glucose 3.9-10mmol/L | 28 days | 
| MARD for Libre and YSI >10mmol/L | Mean absolute relative difference between Libre and YSI glucose >10mmol/L | 28 days | 
| MARD for G6 and YSI 3.9-10mmol/L | Mean absolute relative difference between Dexcom G6 and YSI glucose 3.9-10mmol/L | 28 days | 
| MARD for G6 and YSI >10mmol/L | Mean absolute relative difference between Dexcom G6 and YSI glucose >10mmol/L | 28 days | 
| MARD for G6 and YSI 24hr pre | Mean absolute relative difference between Dexcom G6 and YSI glucose during 24 hours prior to heamodialysis | 24 hours | 
| MARD for Libre and YSI 24hr pre | Mean absolute relative difference between Libre and YSI glucose during 24 hours prior to heamodialysis | 24 hours | 
| MARD for Libre and YSI 24hr post | Mean absolute relative difference between Libre and YSI glucose during 24 hours after heamodialysis | 24 hours | 
| MARD for G6 and YSI 24hr post | Mean absolute relative difference between Dexcom G6 and YSI glucose during 24 hours after heamodialysis | 24 hours | 
| CEG analysis G6 and YSI | Clarke Error Grid analysis between Dexcom G6 and YSI glucose during haemodialysis | 28 DAYS | 
| CEG analysis Libre and YSI | Clarke Error Grid analysis between Libre and YSI glucose during haemodialysis | 28 DAYS | 
| Severe hypoglycaemia | Episodes of severe hypoglycaemia | 28 days | 
| DKA | Diabetic Ketoacidosis | 28 days | 
| Sensor failure | Events of G6/libre sensor failure | 28 days | 
| Missing glucose data | Missing blood glucose data for G6/libre measured by number of missing data points | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes Mellitus, Chronic Kidney Diseases