Effect of Canagliflozin on Ultrafiltration & Fibrosis in Patients on Peritoneal Dialysis

NCT06913647 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-11346
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, proof-of-concept, placebo-controlled, double-blind, cross-over randomized clinical trial, assessing the effect of canagliflozin on peritoneal membrane function in patients on PD. The primary aim of this trial is to determine the short-term effects of canagliflozin, an SGLT-2 inhibitor, on glucose absorption by the peritoneal membrane and on ultrafiltration, as assessed by a standardized peritoneal equilibrium test. The secondary aims are to determine the effect of canagliflozin on solute clearance and on effluent biomarkers of inflammation, angiogenesis, and fibrosis at 26 weeks. We hypothesize that canagliflozin will prevent glucose absorption by the peritoneal membrane, as compared with placebo, and will attenuate the development of inflammation, angiogenesis, and fibrosis of the peritoneal membrane, as assessed by relevant biomarkers in the dialysate.

Conditions

ESRD; CKD (Chronic Kidney Disease) Stage 5D

Keywords

SGLT-2 inhibitors; Canagliflozin; Ultrafiltration failure; Peritoneal fibrosis; Peritoneal dialysis

Outcome Measures

Primary Outcomes (1)

• Change in D4/D0

  Change in the ratio of intraperitoneal glucose at 0 and 4h post infusion (D4/D0 ratio) in a standardized PET with canagliflozin, compared with placebo.

  5 and 10 weeks from baseline

Secondary Outcomes (14)

• Change in ultrafiltration

  5 and10 weeks from baseline

• Change in sodium dip/ sieving

  5 and 10 weeks from baseline

• Change in small solute clearance

  5 and10 weeks from baseline

• Canagliflozin levels in the dialysate

  5 and10 weeks from baseline

• Change in small and middle solute clearance

  26 weeks from baseline

Other Outcomes (1)

• Feasibility outcome

  26 weeks from baseline

Study Arms (3)

Active treatment followed by placebo

ACTIVE COMPARATOR

Canagliflozin 300 mg once daily for 5 weeks (double-blind), followed by matching placebo once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 16 weeks (open label)

Drug: Canagliflozin 300 MG

Placebo followed by active treatment

PLACEBO COMPARATOR

Placebo once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 16 weeks (open label)

Drug: Canagliflozin 300 MG

Standard of care

NO INTERVENTION

Standard of care, with no active treatment, for 26 weeks (open label)

Interventions

Canagliflozin 300 MG DRUG

Canagliflozin 300 mg once daily

Also known as: Invokana 300 mg

Active treatment followed by placebo; Placebo followed by active treatment

Eligibility Criteria

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

You may qualify if:

• Adult patients with kidney failure on PD (both incident and prevalent) who are on a stable prescription of dextrose-based solutions for at least 3 months.
• Only high or high-average transporters, as classified by PET, will be included.

You may not qualify if:

• History of euglycemic ketoacidosis
• Known hypersensitivity to canagliflozin
• Active peritonitis or tunnel infection
• Kidney transplant scheduled in the next 6 months
• Severe liver cirrhosis (Child-Pugh class C stage)
• Recurrent severe genital or urine infections
• Patients receiving digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if these agents cannot be safely discontinued
• Pregnancy or breastfeeding

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Research Institute-McGill University Health Center

Montreal, Quebec, Canada

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency, Chronic; Peritoneal Fibrosis

Interventions

Canagliflozin

Condition Hierarchy (Ancestors)

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; Peritoneal Diseases; Digestive System Diseases; Fibrosis

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Thomas A. Mavrakanas, MD, MSc.

  Research Institute-McGill University of Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Efrosyne Tsirella

CONTACT

514-934-1934; efrosyne.tsirella@muhc.mcgill.ca

Norka Rios

CONTACT

514-934-1934; norka.rios@muhc.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The cross-over part of the study for the assessment of the primary outcome will be blinded (first 10 weeks for arms 1 \& 2). Canagliflozin pills will be encapsulated. For placebo, cellulose will be used to fill identical capsules.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a phase II, proof-of-concept, placebo-controlled, double-blind, cross-over randomized clinical trial.

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: April 6, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: The data may become available twelve months after the end of the study.
• Access Criteria: Any request for data sharing will have to be approved by the clinical trial steering committee after having examined the data sharing proposal. A data use agreement will be required through the Contracts Office of the Research Institute of McGill University Health Center.

Locations

CA (1)