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.
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.
History of euglycemic ketoacidosis
Known hypersensitivity to canagliflozin
Active peritonitis or tunnel infection
Kidney transplant scheduled in the next 6 months
Crossover
Canagliflozin 300 MG
DrugCanagliflozin 300 mg once daily
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.
Change in ultrafiltration
Change in ultrafiltration, as assessed by the volume of drain after a 4h dwell with 2 L of a 2.5% dextrose solution minus the volume infused, with canagliflozin compared with placebo.
Change in sodium dip/ sieving
Change in sodium dip/ sieving, calculated as the absolute difference in dialysate sodium at 0 and 1h post infusion in a standardized PET, with canagliflozin compared with placebo.
Change in small solute clearance
Change in small solute clearance, as assessed by the dialysate-to-plasma (D/P) creatinine and urea at the end of a 4h-dwell, with canagliflozin compared with placebo.
Canagliflozin levels in the dialysate
Canagliflozin levels in the dialysate at 5 and 10 weeks, as assessed by mass spectrometry
Feasibility outcome
Ability to recruit for the study at the anticipated average recruitment rate and study completion with at least 80% adherence with reasons for non-adherence being reported
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McGill University Health Centre/Research Institute of the McGill University Health Centre
Lead sponsor
Canadian Institutes of Health Research (CIHR)
Collaborator
