Effect of Empagliflozin on Peritoneal and Kidney Function in End Stage Renal Disease

Study Overview
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Brief Summary
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The main purpose of the study is to determine if empagliflozin can reduce peritoneal glucose absorption in patients with end stage renal diease (ESRD) on peritoneal dialysis. This is a randomized, placebo controlled, acute crossover study of empagliflozin in an anticipated 30 chronic PD patients, with an 8 week pre post open label extension in all 30 patients where they will receive empagliflozin daily.

Detailed Description
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Participants will undergo three study visits, and up to 4 safety visits, over 9 weeks. At 7 AM in the first study visit, the participants will have taken 25mg empagliflozin once or matching placebo, thus producing peak plasma levels by 10 AM. One week later the participant will return for the crossed over to the alternate study drug. At the conclusion of the 2nd study visit, all participants will be provided with empagliflozin 10mg tabs to be taken daily for 56 days (8 weeks). At each study visit and safety visit, participants will undergo a PET test.

Official Title
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Effect of Empagliflozin on Peritoneal and Kidney Function in End Stage Renal Disease

Conditions
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End Stage Renal Disease on Dialysis

Intervention / Treatment
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* Drug: Empagliflozin 25 mg vs Placebo
* Drug: Empagliflozin 10 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients actively undergoing PD with a reliably functioning PD catheter Stable peritoneal dialysis prescription Chronic loop diuretic usage (at Yale, essentially all patients that make urine are on chronic loop diuretics) PD vintage > 3 months 24 Hour urine output >400 ml Age >18 years of age Exclusion Criteria: History of type 1 diabetes, diabetic ketoacidosis, brittle diabetes or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 6 months Use of an SGLT2 inhibitor within the prior 30 days 1 or more episodes of peritonitis in the previous 6 months or active infection of the peritoneal dialysis catheter Anemia with hemoglobin <8g/dL Inability to give written informed consent or follow study protocol

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, placebo controlled, acute crossover study of empagliflozin in 30 chronic PD patients, with an 8 week pre post open label extension in all 30 patients where they will receive empagliflozin daily.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empagliflozin or Placebo in Acute<br>Acute phase: Participants will receive 25 mg empagliflozin once on Day 0 or Day 7. Participants receive empaglifozin or placebo on Day 0. On Day 7, they will be crossed over to the alternate treatment. | Drug: Empagliflozin 25 mg vs Placebo<br>* Acute Study- Empagliflozin 25 mg vs Placebo on D1 then alternate therapy on D7<br>|
| Active Comparator: Empagliflozin in Chronic<br>Chronic phase: On day 8, all participants will receive 10 mg empagliflozin 10 mg x 8 weeks | Drug: Empagliflozin 10 MG<br>* Chronic Study- Empagliflozin 10 mg for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose absorption with empagliflozin vs. placebo | Total glucose absorption in grams with empagliflozin vs. placebo | Day 0 to Day 63 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ultrafiltration volume with empagliflozin vs. placebo- acute study | Ultrafiltration volume (in liters) at 4 hours with empagliflozin vs. placebo. | at 4 hours | 
| Change in plasma glucose levels with empagliflozin vs. placebo- acute study | Change in plasma glucose levels during PD dwell with empagliflozin vs. placebo- acute study | Day 0 to Day 63 | 
| Increase in natriuresis with empagliflozin vs. placebo-acute study | Natriuresis determined by FENa | Day 0 to Day 63 | 
| Change in peritoneal fluid inflammatory markers | Change in levels of IL-6 and CA-125 (in pg) | Day 0 to Day 63 | 
| Change in PET test parameters | Change in peritoneal equilibration test parameters, measurement of solute transport across the peritoneal membrane (standard test carried out in PD patients to assess solute trasnport across membrane) | Day 0 to Day 63 | 
| Change in total body water and extracellular water | Change in total body water and extracellular water, using heaving water (D20) | Day 0 to Day 63 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peritoneal dialysis