A Study to Investigate the Mechanistic Effects of Dapagliflozin Alone or in Combination With Balcinrenone, Compared to Balcinrenone and Placebo on Body Fluid and Electrolyte Handling and Energy Metabolism in Participants Over 50 Years of Age With Chronic Kidney Disease. — DapaBalci-Leap  

Chronic Renal Failure Clinical Trial

Official title: Natriuretic-ureothelic Adaptation of Body Fluid Homeostasis During SGLT-2 Inhibition and/or Mineralocorticoid Receptor Modulation in Patients With Chronic Kidney Disease. A 4-arm, Double-blind, Double-dummy, Parallel-group, Phase 2 Study to Investigate the Mechanistic Effects of Dapagliflozin, Dapagliflozin + Balcinrenone, Balcinrenone and Placebo on Body Solute and Water Homeostasis and Energy Metabolism in Male and Female Participants Over 50 Years of Age With Chronic Kidney Disease.

Status Recruiting

Clinical Trial Summary

The purpose of this study is to investigate the mechanistic effects of dapagliflozin 10 mg, alone or in combination with balcinrenone 150 mg, with balcinrenone 150 mg and placebo, on the way the body handles electrolytes and water content, as well as the effects these interventions may have on energy metabolism in participants with stage 3 chronic kidney disease. The study interventions will be administered orally, daily, in addition to current therapy, for a duration of 28 days. This will allow us to maximize our ability to detect a drug effect while minimizing the drop-out rate that accompanies longer studies. In order to understand the different mechanistic effects of these interventions on energy metabolism, the study will be conducted at two study sites. The study design and treatment allocation, treatment duration as well as sample analysis for evaluation of the primary endpoint will be identical for all participants, at both sites. Therefore, urine and plasma samples for analysis of water and electrolyte handling will be collected from all study participants at both sites.

In addition to the primary endpoint, the main study site (Nuremberg) will conduct a metabolic study to investigate the early- and late-effects of the interventions, while the second site, Marseille, will conduct an imaging sub-study to assess changes at the tissue level before and after treatment.

Clinical Trial Description

The Nuremberg site will perform metabolomics analyses and evaluation of metabolic longevity switches in erythrocytes; participants will be randomly allocated to 1 of the 4 treatment arms, with n=20 participants per arm. All participants in Nuremberg will undergo 3 study visits: at baseline, day 3 (to study the early effect of the intervention) and at day 28 (for the late metabolic effects). An additional safety study visit will take place at day 7+/-1. A follow-up visit will take place at day 28 +/- 7 after the last dose. Study procedures: medical examination, height, weight, blood pressure (BP), heart rate (HR), 24h urine collection and analysis, venous blood sampling. This site will prepare venous blood samples for metabolomic analysis and will perform the erythrocyte isolation protocol for the assessment of erythrocyte metabolism. The Marseille site will conduct an imaging sub-study to evaluate tissue sodium and water content, and muscle energy metabolism before and after the study intervention; participants will be randomly allocated to 1 of the 4 treatment arms, with n=10 participants per arm.

All participants in Marseille will undergo 2 study visits: at baseline (before starting the intervention) and after 28 days of treatment. An additional safety study visit will take place at day 7+/-1. A follow-up visit will take place at day 28 +/- 7 after the last dose.

Study procedures: medical examination, height, weight, blood pressure, heart rate, 24h urine collection and analysis, venous blood sampling, MRI scans.

During each of the study visits at baseline and day 28 the participants will undergo 2 MRI scans:

a 23Na MRI scan for the assessment of tissue sodium storage and water content at ultra-high field (7T MRI) and a spectroscopy scan for the assessment of muscle energy metabolism (phosphorus spectroscopy at 3T). The total duration of the scans at each study visit will be approximately 2h. A maximum of 150 participants will be assigned to investigational intervention, to account for a 20% drop-out rate after initiation of the investigational intervention. A total of 120 participants (30 per arm) would be needed to complete the study. Enrolled means participants' or their legally acceptable representatives' agreement to participate in a clinical study following completion of the informed consent process. Potential participants who are screened for the purpose of determining eligibility for the study, but do not participate in the study, are not considered enrolled, unless otherwise specified by the protocol. A participant will be considered enrolled if the informed consent is not withdrawn prior to participating in any study activity after screening.

Participants in this study will be randomized into one of the 4 treatment arms:

1. Balcinrenone 150 mg (n=30)

2. Balcinrenone 150 mg + Dapagliflozin 10 mg (n=30)

3. Dapagliflozin 10 mg (n=30)

4. Placebo (n=30) For each group, 20 participants per group will complete the study in Nuremberg (total n=80) and 10 participants per group will complete the study in Marseille (total n=40). No dose modification, neither for dapagliflozin nor for balcinrenone, is planned during this study.

To ensure a dose interval of about 24 hours, the medication should be taken every day in the morning. If a dose is missed by more than 12 hours, that dose should be skipped and the next dose should be taken as scheduled. No double doses should be taken. Because of the short treatment duration in this study (28 days) no temporary discontinuation can take place, as this can affect the metabolic phenotype at day 3 and day 28. Therefore, if a participant needs to discontinue the study intervention, this participant will be withdrawn from the study and replaced. Treatment duration will be 28 days, up to a maximum of 32 days to allow for scheduling flexibility.

A follow-up visit will take place approximately one month (28 days +/-7 days) after the end of the intervention period. The screening visit may take place anytime within 4 weeks prior to Baseline visit. Therefore, the estimated total study duration for each participant, including screening and follow-up is 2 to 3 months. ;

Related Conditions & MeSH terms

• Chronic Renal Failure
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

• NCT number: NCT05884866
• Study type: Interventional
• Source: Klinikum Nürnberg
• Contact: Dominik Zaremba
• Phone: +499113985403
• Email: dominik.zaremba@klinikum-nuernberg.de
• Status: Recruiting
• Phase: Phase 2
• Start date: May 8, 2023
• Completion date: January 31, 2025