CANagliflozin In DIALysis Patients

NCT07527390 | Not Yet Recruiting Phase 4

• 2 other identifiers: 207252025-522742-46-00
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a relatively new class of drugs originally developed for the treatment of diabetes. Cardiovascular outcome trials with these drugs showed also beneficial effects of these agents on heart failure, cardiovascular disease and kidney outcomes. Secondary analyses from these trials demonstrated that these benefits were consistent in patients with or without type 2 diabetes and with or without chronic kidney disease (CKD) with a lower eGFR threshold of 20 mL/min/1.73m2. However, it is not yet clear if these drugs can also be used in patients with severe kidney disease who require dialysis. This is in part explained because SGLT2 inhibitors bind to a transporter which is located in the luminal side of proximal tubes in the kidney. If kidney function is low, and these patients have no or limited filtering capacity, it is possible that the efficacy of these drugs decrease. Notwithstanding, several animal experiments and preliminary clinical data have suggested that these drugs do have kidney and cardiac protective effects in case of severely decreased kidney function. The investigators hypothesize that SGLT2 inhibitors are distributed to several tissues in the body on top of the kidney and therefore the investigators would like to investigate the specific tissue distribution of SGLT2 inhibitors in patients on dialysis with-and without residual diuresis.

Conditions

Dialysis; Chronic Kidney Disease (Stages 4 and 5)

Keywords

SGLT2 inhibitors; PET imaging

Outcome Measures

Primary Outcomes (1)

• Overall drug tissue disposition of SGLT2 in patients on dialysis.

  The main outcome of the study is overall drug tissue disposition of SGLT2 in patients on dialysis. quantified by images obtained by PET imaging.

  From enrollment to the second study day, seperated by approximately one-week intervals.

Secondary Outcomes (1)

• Receptor occupancy of SGLT2 in the regions of interest.

  From enrollment to the second study day, seperated by approximately one-week intervals.

Study Arms (1)

Radiotracer 18F- canagliflozin

EXPERIMENTAL

On the first study day the radiotracer 18F- canagliflozin will be administered intravenously. On the second study day, following oral administration of 600 mg of canagliflozin, a second radiotracer dose of 18F- canagliflozin will be administered intravenously.

Drug: Invokana 300 mg and 100 mg tablet

Interventions

Invokana 300 mg and 100 mg tablet DRUG

A 600 mg dose of canagliflozin (two 300 mg tablets) will be administered orally by the participant

Radiotracer 18F- canagliflozin

Eligibility Criteria

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

You may qualify if:

• Hemodialysis for more than 3 months (5 also with residual diuresis)
• Age ≥18 years of age
• Willing to sign informed consent

You may not qualify if:

• Mentally incapacitated subjects (i.e. not able to sign informed consent)
• Subjects who participated in a trial with exposure to radiation before, are only allowed to participate if the total cumulative radiation burden in their life does not exceed 1 mSv per year, counting from the age of 18 years.
• Pregnant women and women of child-bearing potential who are not using reliable contraception
• Subjects on diuretics are allowed to participate but the dose should be stable for at least 4 weeks prior to screening
• Subjects already on a SGLT2 inhibitor are allowed to participate, but the drug should be inter-rupted 1 week prior to the first study day till the end of the second study day (as the half-life is 10-13 hours a wash-out of the study drug of at least 7-days should be considered)
• History of hypersensitivity to canagliflozin or another SGLT2 inhibitor
• Severe claustrophobia
• History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
• Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
• Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months
• Pancreatic injury or pancreatitis within the last six months
• Use of rifampicin and cholestryramine
• Established peripheral arterial disease
• People using digoxin and/or lithium

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9713 GZ, Netherlands

Location

Related Publications (8)

• Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-2306. doi: 10.1056/NEJMoa1811744. Epub 2019 Apr 14.

  PMID: 30990260 BACKGROUND

• Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.

  PMID: 32970396 BACKGROUND

• The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4.

  PMID: 36331190 BACKGROUND

• Juni RP, Al-Shama R, Kuster DWD, van der Velden J, Hamer HM, Vervloet MG, Eringa EC, Koolwijk P, van Hinsbergh VWM. Empagliflozin restores chronic kidney disease-induced impairment of endothelial regulation of cardiomyocyte relaxation and contraction. Kidney Int. 2021 May;99(5):1088-1101. doi: 10.1016/j.kint.2020.12.013. Epub 2020 Dec 23.

  PMID: 33359500 BACKGROUND

• Uthman L, Homayr A, Juni RP, Spin EL, Kerindongo R, Boomsma M, Hollmann MW, Preckel B, Koolwijk P, van Hinsbergh VWM, Zuurbier CJ, Albrecht M, Weber NC. Empagliflozin and Dapagliflozin Reduce ROS Generation and Restore NO Bioavailability in Tumor Necrosis Factor alpha-Stimulated Human Coronary Arterial Endothelial Cells. Cell Physiol Biochem. 2019;53(5):865-886. doi: 10.33594/000000178.

  PMID: 31724838 BACKGROUND

• Billing AM, Kim YC, Gullaksen S, Schrage B, Raabe J, Hutzfeldt A, Demir F, Kovalenko E, Lasse M, Dugourd A, Fallegger R, Klampe B, Jaegers J, Li Q, Kravtsova O, Crespo-Masip M, Palermo A, Fenton RA, Hoxha E, Blankenberg S, Kirchhof P, Huber TB, Laugesen E, Zeller T, Chrysopoulou M, Saez-Rodriguez J, Magnussen C, Eschenhagen T, Staruschenko A, Siuzdak G, Poulsen PL, Schwab C, Cuello F, Vallon V, Rinschen MM. Metabolic Communication by SGLT2 Inhibition. Circulation. 2024 Mar 12;149(11):860-884. doi: 10.1161/CIRCULATIONAHA.123.065517. Epub 2023 Dec 28.

  PMID: 38152989 BACKGROUND

• Bakker WM, Heerspink HJL, Berger SP, Wanner C, Badve SV, Arnott C, Abrahams AC, van den Born JC, van Faassen TC, Gaillard CAJM, Gelens MACJ, Gorris JL, Hemmelder MH, Jakulj L, van Kruijsdijk RCM, Kuypers DRJ, van der Meer P, van der Net JB, Nijmeijer HH, Vervloet MG, de Vries APJ, Walsh M, Wang AY, Gansevoort RT; Renal Lifecycle Trial Investigators. Rationale and design of the Renal Lifecycle trial assessing the effect of dapagliflozin on cardiorenal outcomes in severe chronic kidney disease. Nephrol Dial Transplant. 2025 Aug 29;40(9):1746-1755. doi: 10.1093/ndt/gfaf046.

  PMID: 40053493 BACKGROUND

• van der Hoek S, Willemsen ATM, Visser T, Heeres A, Mulder DJ, Bokkers RPH, Slart RHJA, Elsinga PH, Heerspink HJL, Stevens J. Feasibility Study to Assess Canagliflozin Distribution and Sodium-Glucose Co-Transporter 2 Occupancy Using [18 F]Canagliflozin in Patients with Type 2 Diabetes. Clin Pharmacol Ther. 2023 Jun;113(6):1295-1303. doi: 10.1002/cpt.2886. Epub 2023 Mar 26.

  PMID: 36897753 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Canagliflozin; Tablets

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Hiddo Lambers Heerspink, Prof.

CONTACT

+31 50 361 4071; h.j.lambers.heerspink@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)