Effect of Empagliflozin on Peritoneal and Kidney Function in End Stage Renal Disease (EMPA-PD)

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.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease on Dialysis
• Intervention / Treatment: Drug: Empagliflozin 25 mg vs Placebo; Drug: Empagliflozin 10 MG

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Katherine Keith; Phone Number: 203-737-3571; Email: katherine.keith@yale.edu
• Study Contact Backup: Name: Veena Rao, PHD; Phone Number: 203-737-3571; Email: veena.s.rao@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University
      • Contact: Katherine Keith

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Patients actively undergoing PD with a reliably functioning PD catheter
2. Stable peritoneal dialysis prescription
3. Chronic loop diuretic usage (at Yale, essentially all patients that make urine are on chronic loop diuretics)
4. PD vintage > 3 months
5. 24 Hour urine output >400 ml
6. Age >18 years of age

Exclusion Criteria:

1. 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
2. Use of an SGLT2 inhibitor within the prior 30 days
3. 1 or more episodes of peritonitis in the previous 6 months or active infection of the peritoneal dialysis catheter
4. Anemia with hemoglobin <8g/dL
5. Inability to give written informed consent or follow study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin or Placebo in Acute; 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; Acute Study- Empagliflozin 25 mg vs Placebo on D1 then alternate therapy on D7
Active Comparator: Empagliflozin in Chronic; Chronic phase: On day 8, all participants will receive 10 mg empagliflozin 10 mg x 8 weeks	Drug: Empagliflozin 10 MG; Chronic Study- Empagliflozin 10 mg for 8 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Boehringer Ingelheim
• Investigators: Principal Investigator: Jeffrey Testani, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 14, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Peritoneal dialysis
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 2000031605

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No