Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment

NCT05250752 | Unknown Phase 2

• 1 other identifier: HOL-MED-01-2021
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

End stage renal disease is annually diagnosed in about one thousand patients in Denmark, and one of the treatment modalities in renal replacement therapy is peritoneal dialysis with about 25 % of patients assigned to this treatment (Hommel2010). Peritoneal dialysis is based on the principle of filtering waste products to peritoneal fluid and by exchange of peritoneal fluid eliminate waste products from the body. In peritoneal dialysis commonly used fluids contain glucose. Exposure to high glucose levels in peritoneal fluid during peritoneal dialysis has several side effects. Primarily, as glucose passes over and into the peritoneal membrane it causes local inflammation which leads to fibrosis over time (Zhou2016). Fibrosis limits the capacity of the exchange of water and waste products over the peritoneal membrane. The decrease of peritoneal exchange capacity is most commonly the reason for termination of peritoneal dialysis. SGLT2-channels are identified in peritoneal mesothelial cells of rats (Debray-Carcia 2016), and most recently also in humans (Shentu2021). An in vitro model of human peritoneal mesothelial cells incubated with the SGLT2-inhibitor (empagliflozin) has shown significantly decrease in glucose uptake (Zhou2019). Exposure to intraperitoneal empagliflozin in rats, reduced the uptake of glucose over the peritoneal membrane significantly by 78 % and the ultrafiltration was increased (Zhou2019). Currently, to our knowledge, no clinical trials have been conducted in humans attending peritoneal dialysis with the aim of investigating either the effect or safety of SGLT2i, as it is indeed the first of its kind, with the aim of including participants in peritoneal dialysis.

Conditions

End Stage Renal Disease; Peritoneal Dialysis Complication

Keywords

SGLT2-inhibition; dapagliflozin

Outcome Measures

Primary Outcomes (1)

• Peritoneal glucose uptake (mg/ dL)

  Glucose level in peritoneal fluid during a four hour standardized peritoneal dialysis. Change in total glucose uptake before and after treatment (treatment periode of three days)

  Day 0 (baseline), Day 3 (max dose of treatment)

Secondary Outcomes (4)

• Fluid volume (ml)

  Measured at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment)

• Plasma glucose level (mg/ dL)

  Measured at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment).

• Pharmacokinetics (nmol)

  Samples for biobank - samples drawn at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment). Samples are drawn every 30 minuttes during each peritoneal dialysis.

• Adverse events (events)

  At day 1 (first day of treatment), day 3 (max dose of treatment) and day 30 (four weeks after treatment)

Study Arms (1)

On treatment

OTHER

Assigned to oral treatment with dapagliflozin 10 mg for three consecutive days.

Drug: Dapagliflozin 10 MG [Farxiga]

Interventions

Dapagliflozin 10 MG [Farxiga] DRUG

Primary end-points are measure before (day 0), on treatment (day 1 and day 3) and after treatment (day 21)

On treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age above 18 years of age
• In stable peritoneal dialysis for more than 14 days.

You may not qualify if:

• In treatment with SGLT2i currently or within the last 90 days.
• Treatment for peritoneal infection within the last 30 days.
• Any hospitalization within the last 30 days.
• Anaphylaxis to the IMP.
• Impaired lever function with ALAT above normal range within the last 6 month.
• Sever efflux problems during peritoneal dialysis for the last 14 days, judged by the investigator.
• Non-menopausal defined as menstruation within the last 12 month without any other medical cause. Only applicable for female participants.
• Substance abuse, judged by the investigator.
• Incapable to follow study protocol, judged by the investigator.
• Previously included in this clinical trial and exposed to the IMP.
• Included in another clinical trial with exposure to any IMP within the last 30 days.

Sponsors & Collaborators

• Holbaek Sygehus: lead

Study Sites (1)

University Hospital Copenhagen - Holbaek

Holbæk, Region Sjælland, 4300, Denmark

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Morten Lindhardt, MD, PhD

  Copenhagen University Hospital - Holbaek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cross-over. Off-On-Off treatment. Dose response

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: February 22, 2022
• Study Start: November 18, 2021
• Primary Completion: February 27, 2022
• Study Completion: December 31, 2022
• Last Updated: February 22, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Depended on the request - Days to weeks
• Access Criteria: Not conflict with the anonymity and confidentiality of the data and a signed contract for data sharing.

Locations

DK (1)