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

Chronic Kidney Diseases Clinical Trial

— ALPHA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03885362
• Other study ID #: 18SM4938
• Status: Completed
• Phase: N/A
• Start date: December 11, 2019
• Est. completion date: July 1, 2022

Study information

• Verified date: August 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 1, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Nephropathies
• Kidney Diseases
• Renal Insufficiency, Chronic
• Type 1 Diabetes Mellitus

Intervention

Device:
• Dexcom G6 and Abbott Freestyle Libre
Dexcom G6 - continuous glucose monitoring device - blinded. CE mark 2018 Abbott Freestyle Libre - flash glucose monitoring device. CE mark 2014

Locations

Country	Name	City	State
United Kingdom	Imperial College London/NHS trust Renal Unit	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (11)

Beck RW, Riddlesworth T, Ruedy K, Ahmann A, Bergenstal R, Haller S, Kollman C, Kruger D, McGill JB, Polonsky W, Toschi E, Wolpert H, Price D; DIAMOND Study Group. Effect of Continuous Glucose Monitoring on Glycemic Control in Adults With Type 1 Diabetes Using Insulin Injections: The DIAMOND Randomized Clinical Trial. JAMA. 2017 Jan 24;317(4):371-378. doi: 10.1001/jama.2016.19975. — View Citation

Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47. — View Citation

Creme D, McCafferty K. Glycaemic Control Impact on Renal Endpoints in Diabetic Patients on Haemodialysis. Int J Nephrol. 2015;2015:523521. doi: 10.1155/2015/523521. Epub 2015 Sep 20. — View Citation

Haviv YS, Sharkia M, Safadi R. Hypoglycemia in patients with renal failure. Ren Fail. 2000 Mar;22(2):219-23. — View Citation

Inaba M, Okuno S, Kumeda Y, Yamada S, Imanishi Y, Tabata T, Okamura M, Okada S, Yamakawa T, Ishimura E, Nishizawa Y; Osaka CKD Expert Research Group. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007 Mar;18(3):896-903. Epub 2007 Jan 31. — View Citation

Joy MS, Cefalu WT, Hogan SL, Nachman PH. Long-term glycemic control measurements in diabetic patients receiving hemodialysis. Am J Kidney Dis. 2002 Feb;39(2):297-307. — View Citation

Lee KF, Szeto YT, Benzie IF. Glycohaemoglobin measurement: methodological differences in relation to interference by urea. Acta Diabetol. 2002 Apr;39(1):35-9. — View Citation

Levin A. Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis. Semin Dial. 2003 Mar-Apr;16(2):101-5. Review. — View Citation

Lind M, Polonsky W, Hirsch IB, Heise T, Bolinder J, Dahlqvist S, Schwarz E, Ólafsdóttir AF, Frid A, Wedel H, Ahlén E, Nyström T, Hellman J. Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections: The GOLD Randomized Clinical Trial. JAMA. 2017 Jan 24;317(4):379-387. doi: 10.1001/jama.2016.19976. Erratum in: JAMA. 2017 May 9;317(18):1912. — View Citation

National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012 Nov;60(5):850-86. doi: 10.1053/j.ajkd.2012.07.005. Erratum in: Am J Kidney Dis. 2013 Jun;61(6):1049. — View Citation

Pickup JC, Freeman SC, Sutton AJ. Glycaemic control in type 1 diabetes during real time continuous glucose monitoring compared with self monitoring of blood glucose: meta-analysis of randomised controlled trials using individual patient data. BMJ. 2011 Jul 7;343:d3805. doi: 10.1136/bmj.d3805. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

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