Continuous Glucose Monitoring in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes

Study Overview
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Brief Summary
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Twenty participants with end stage kidney disease (ESKD) and burnt-out diabetes, and 20 non-diabetic participants with ESKD will wear a continuous glucose monitoring (CGM) device for 10 days to see if the use of CGM is a better tool to assess glycemic control than glycosylated hemoglobin (HbA1c) in patients with ESKD on dialysis.

Detailed Description
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More than 37 million adults, or 14.7% of all Americans aged 18 and older, are living with diabetes. Controlling hyperglycemia is foundational to diabetes management and is necessary to reduce the risks of chronic diabetes complications and death. Diabetic nephropathy accounts for great morbidity, as diabetes is the number one cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the United States. It is estimated that diabetes affects up to 40% of patients with ESKD. Assessment of glucose control in patients with advanced CKD/ESKD is complex due to changes in glucose homeostasis, potential effects on assays of glycemia, and altered pharmacokinetics of diabetes medications. Glycosylated hemoglobin (HbA1c) has been the gold standard to assess glycemic control in patients with diabetes. HbA1c reflects the average glycemic value over approximately 3 months. Although HbA1c is associated with chronic complications of diabetes in patients with normal kidney function, its predictive value is uncertain in patients with ESKD. Continuous glucose monitoring (CGM) technology in the outpatient setting has transformed glucose monitoring for diabetes self-management, providing more comprehensive glycemic control data than intermittent point-of-care capillary blood glucose monitoring and HbA1c. Once progressed to ESKD, up to one fourth of patients experience resolution of their hyperglycemia, as defined by an HbA1c level of less than 6.5%, and consequently are no longer on antidiabetic agents and insulin. This phenomenon is known as burnt-out diabetes which is likely due to various underlying factors, including but not limited to, malnutrition, reduced clearance and degradation of insulin, decreased kidney gluconeogenesis, and accumulation of uremic toxins. These patients are likely at a greater risk of morbidity and mortality and an increased risk of hypoglycemic episodes. There is a need for further research in patients with ESKD to establish what is the most appropriate tool to assess glycemic control in those with 'burnt-out diabetes'. This study will use CGM to measure patients' glucose with real-time levels as opposed to relying on surrogate markers like HbA1c. These results can give insight into the reality of glycemic control in these patients and can impact the best monitoring and treatment for patients with burnt-out diabetes. It is not known if patients with burnt-out diabetes have complete normoglycemia or if they may have episodes of (untreated) hyperglycemia, which may be associated with poor outcomes. The researchers of this study will compare glycemic control by CGM in patients with burnt-out diabetes and non-diabetic patients with ESKD.

Official Title
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Continuous Glucose Monitoring in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes

Conditions
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End Stage Kidney Disease

Intervention / Treatment
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* Device: Continuous glucose monitoring (CGM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dialysis treatment for more than 3 months HbA1c less than 6.5% at the first clinic visit Willing to wear a CGM for 10 days Exclusion Criteria: Have used insulin or any diabetes treatment during the last 3 months Be pregnant or plan to become pregnant during the study Known allergy to medical-grade adhesives Taking acetaminophen (more than 1 gram every six hours) or hydroxyurea (may interfere with sensor membrane) Current or anticipated use of stress steroid doses (prednisone </= 5 mg or its equivalent is allowed)

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: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESKD with Burnt-out Diabetes<br>Participants with ESKD and burnt-out diabetes wearing a CGM for 10 days. | Device: Continuous glucose monitoring (CGM)<br>* The Dexcom G6 CGM system is a compact, light-weight glucose testing device that measures glucose every 5 minutes. Participants will wear the CGM with the display off for 10 days while continuing their routine dialysis sessions.<br>* Other names: Dexcom G6 CGM;|
| Experimental: ESKD without Diabetes<br>Non-diabetic participants with ESKD wearing a CGM for 10 days. | Device: Continuous glucose monitoring (CGM)<br>* The Dexcom G6 CGM system is a compact, light-weight glucose testing device that measures glucose every 5 minutes. Participants will wear the CGM with the display off for 10 days while continuing their routine dialysis sessions.<br>* Other names: Dexcom G6 CGM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia Event Rate | Hypoglycemia is defined as blood glucose < 70 mg/dL and is assessed by Dexcom G6 CGM. The hypoglycemic event rate is defined as the number of hypoglycemic events per patient per day. | Up to Day 10 | 
| Nocturnal Hypoglycemia Event Rate | Hypoglycemia is defined as blood glucose < 70 mg/dL and is assessed by Dexcom G6 CGM. A nocturnal hypoglycemia episode is defined as an episode occurring during the time interval of 10:00 Post Meridiem (PM) to 6:00 Ante Meridiem (AM). The hypoglycemic event rate is defined as the number of hypoglycemic events per patient per day. | Up to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Daily Blood Glucose Concentration | Glycemic control is assessed as mean daily glucose concentration, measured by Dexcom G6 CGM. | Up to Day 10 | 
| Hemoglobin A1C (HbA1C) | The most recent HbA1c value will be compared between study arms. Normal values are less than 5.7%, while values of 6.5% and above indicate diabetes. | Up to Day 10 | 
| Comorbidities | A composite of comorbidities of hypertension, cardiovascular disease, heart failure, peripheral neuropathy, autonomic/GI neuropathy, cerebrovascular disease, peripheral vascular disease, depression, anxiety, and cognitive impairment/dementia will be compared between study arms. | Up to Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burnt-out diabetes, Dialysis, End stage renal disease, Kidney failure