Canagliflozin for Chronic Kidney Disease

(CAN-PD Trial)

Overseen By Norka Rios

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Digoxin, Phenobarbital, Phenytoin, others

Disqualifiers: Euglycemic ketoacidosis, Severe liver cirrhosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 26 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if they cannot be safely discontinued. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Canagliflozin for chronic kidney disease?

Research shows that Canagliflozin, originally used to lower blood sugar in type 2 diabetes, also helps protect the kidneys. Studies found it reduces the risk of kidney problems in people with diabetes, and a specific trial showed it slows kidney disease progression in diabetic kidney disease. ^{1 2 3 4 5}

Is canagliflozin safe for humans?

Canagliflozin has been shown to be generally safe in humans, with known side effects like genital infections and a noted increased risk of amputations that needs more study. It has been used in people with type 2 diabetes and chronic kidney disease, showing benefits for heart and kidney health. ^{3 4 6 7 8}

How is the drug canagliflozin unique for treating chronic kidney disease?

Canagliflozin is unique because it is a sodium glucose co-transporter 2 inhibitor that not only lowers blood sugar in type 2 diabetes but also offers kidney protection by promoting the excretion of glucose through urine. This dual action makes it different from traditional treatments that primarily focus on blood pressure control to slow kidney disease progression. ^{3 4 5 8 9}

What is the purpose of this trial?

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.

Research Team

Thomas A. Mavrakanas, MD, MSc.

Principal Investigator

Research Institute-McGill University of Health Centre

Eligibility Criteria

This trial is for patients on peritoneal dialysis who may have conditions like chronic kidney disease or renal disease. Participants should not have contrast-induced nephropathy or thyroid fibrosis. The study seeks individuals to test the effects of a drug called Canagliflozin.

Inclusion Criteria

I have kidney failure, am on PD, and have used dextrose-based solutions for 3+ months.

Only high or high-average transporters, as classified by PET, will be included

Exclusion Criteria

I have had ketoacidosis with normal blood sugar levels before.

Pregnancy or breastfeeding

Known hypersensitivity to canagliflozin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive canagliflozin or placebo for 5 weeks, followed by crossover to the alternate treatment for another 5 weeks, and then canagliflozin for 16 weeks

26 weeks

4 visits (in-person), 1 visit (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Canagliflozin

Trial Overview The trial tests Canagliflozin, an SGLT-2 inhibitor, against a placebo to see if it affects glucose absorption and ultrafiltration in the peritoneum. It's double-blind and cross-over, meaning neither doctors nor patients know who gets the real drug at first, then they switch.

Participant Groups

Group I: Active treatment followed by placebo Active Control 1 Intervention

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)

Group II: Standard of care Active Control 1 Intervention

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

Group III: Placebo followed by active treatment Placebo Group 1 Intervention

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)

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

Canagliflozin significantly reduces the risk of cardiovascular events and kidney outcomes in individuals with type 2 diabetes, showing a consistent relative effect across different KDIGO risk categories based on kidney function and albumin levels.

Higher KDIGO risk categories experienced greater absolute reductions in cardiovascular outcomes, suggesting that patients with more severe kidney disease may benefit more from canagliflozin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Neuen, BL., Ohkuma, T., Neal, B., et al.[2021]

Canagliflozin significantly improved glycemic control in patients with type 2 diabetes and stage 3 chronic kidney disease, reducing HbA1c levels compared to placebo after 26 weeks.

The treatment was generally well tolerated, with similar rates of adverse events compared to placebo, although there were slightly higher instances of urinary tract infections and other osmotic diuresis-related effects at the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Yale, JF., Bakris, G., Cariou, B., et al.[2022]

Canagliflozin, an SGLT-2 inhibitor, showed potential in improving kidney function in rats with non-diabetic chronic kidney disease (CKD) induced by adenine, significantly reducing inflammation and oxidative stress markers.

The drug did not cause any significant adverse effects, suggesting it may be safe for further investigation in human trials for CKD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats. Ali, BH., Al Salam, S., Al Suleimani, Y., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Canagliflozin for the Treatment of Diabetic Kidney Disease and Implications for Clinical Practice: A Narrative Review. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Renal effects of canagliflozin in type 2 diabetes mellitus. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

SGLT2 Inhibitors to Slow Chronic Kidney Disease Progression: A Review. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Canagliflozin review - safety and efficacy profile in patients with T2DM. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats. [2020]