Clinical trial NCT03885362: Assessment of the Accuracy of Continuous Glucose Sensors in People With Diabetes Undergoing Haemodialysis
Official title: Assessment of the Accuracy of Continuous Glucose Sensors in People With Diabetes Undergoing Haemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Nephropathies
Type 1 Diabetes Mellitus
Chronic Kidney Diseases
Keywords: Type 1 Diabetes Mellitus
Chronic Kidney Diseases
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2019-03-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: MARD between G6 and YSI
timeFrame: 28 days
measure: MARD between Libre and YSI
timeFrame: 28 days
Secondary outcomes:
measure: HbA1c
timeFrame: 28 days
measure: MARD for G6 and YSI <3.9mmol/L
timeFrame: 28 days
measure: MARD for Libre and YSI <3.9mmol/L
timeFrame: 28 days
measure: MARD for Libre and YSI 3.9-10mmol/L
timeFrame: 28 days
measure: MARD for Libre and YSI >10mmol/L
timeFrame: 28 days
measure: MARD for G6 and YSI 3.9-10mmol/L
timeFrame: 28 days
measure: MARD for G6 and YSI >10mmol/L
timeFrame: 28 days
measure: MARD for G6 and YSI 24hr pre
timeFrame: 24 hours
measure: MARD for Libre and YSI 24hr pre
timeFrame: 24 hours
measure: MARD for Libre and YSI 24hr post
timeFrame: 24 hours
measure: MARD for G6 and YSI 24hr post
timeFrame: 24 hours
measure: CEG analysis G6 and YSI
timeFrame: 28 DAYS
measure: CEG analysis Libre and YSI
timeFrame: 28 DAYS
measure: Severe hypoglycaemia
timeFrame: 28 days
measure: DKA
timeFrame: 28 days
measure: Sensor failure
timeFrame: 28 days
measure: Missing glucose data
timeFrame: 28 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London/NHS trust Renal Unit
Study officials:
affiliation: Imperial College London
name: Nick Oliver
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1001/jama.298.17.2038.
citation: Levin A. Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis. Semin Dial. 2003 Mar-Apr;16(2):101-5. doi: 10.1046/j.1525-139x.2003.16025.x.
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.
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.
citation: Haviv YS, Sharkia M, Safadi R. Hypoglycemia in patients with renal failure. Ren Fail. 2000 Mar;22(2):219-23. doi: 10.1081/jdi-100100866.
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. doi: 10.1007/s005920200010.
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. doi: 10.1681/ASN.2006070772. Epub 2007 Jan 31.
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. doi: 10.1053/ajkd.2002.30549.
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.
citation: 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.
citation: Lind M, Polonsky W, Hirsch IB, Heise T, Bolinder J, Dahlqvist S, Schwarz E, Olafsdottir AF, Frid A, Wedel H, Ahlen E, Nystrom 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.