Beneficial Effect of Amiloride on Progression of Chronic Kidney Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorOdense University Hospital
About this trial
This is a randomized, placebo-controlled, double-blinded crossover trial testing the effects of amiloride in patients with chronic kidney disease (CKD) and proteinuria.
In CKD with proteinuria, there is aberrant filtration of serine proteases and complement precursors into the tubular lumen. The interaction of these factors leads to proinflammatory complement activation, which may promote inflammation, opsonization, and formation of the membrane-attack complex, causing cell injury.
With the aim of preserving kidney function, reducing cardiovascular morbidity, and delaying renal replacement therapy in CKD, this study tests whether amiloride (10 mg/day) protects the filtration barrier, lowers albuminuria, and mitigates kidney inflammation through urokinase inhibition, independent of blood pressure effects.
Participants are randomized to receive amiloride (10 mg/day) or placebo for one week, with a 2-3-week washout period in between. Blood and urine samples are collected before and after each treatment period. Additionally, ECG, body composition measurements, blood pressure, and body weight are monitored.
The primary outcome measures are urinary C3a, soluble C5-9 (sTCC/MAC), and kidney injury biomarkers KIM-1 and NGAL. Secondary endpoints include the urinary albumin/creatinine ratio, protein/creatinine ratio, and blood pressure.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participant must be 18 years of age including at the time of signing the informed consent.
eGFR ≥ 25 mL/min/1.73m2 and < 60mL/ min/1.73m2 at screening
UACR of ≥ 300mg/g at screening
Participants must be on stable antihypertensive treatment 2 weeks before start of study drug and throughout study duration.
Disqualifiers
Treatment with amiloride alone or in combination or use of other types of K-sparing diuretics, MR antagonists (Spironolactone, eplerenone, finerenone)
Ongoing cancer treatment
Treatment with immunosuppressive therapy within 6 months prior to screening
History of organ transplantation
Trial design
Design model
Crossover
Treatments tested in this trial
amiloride
Drug5mg twice daily for 7 days
Placebo
Drug1 tablet twice daily for 7 days
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: AmilorideExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Urine-C3a (ng/ml)
Urine-C3a is measured in spot urine samples and expressed as u-C3a/creatinine (µg/g) to account for the dilution factor.
Time frame
Measured before (day one) and after (day 8) each treatment period2
Urine C5-9-sTCC/MAC (U/ml)
Membrane Attack Complex (MAC) of the complement system, specifically targeting the C5 to C9 proteins. u-C5-9 is measured in spot urine samples and expressed as u-C5-9/creatinine U/µmol to account for the dilution factor.
Time frame
Measured before (day one) and after (day 8) each treatment period3
Kidney Injury Molecule-1 (KIM-1) pg/ml
KIM-1 is a protein that serves as a biomarker used particularly in the context of kidney injury
Time frame
Measured before (day one) and after (day 8) each treatment period4
Neutrophil Gelatinase-Associated Lipocalin (NGAL) (pg/mL)
NGAL is a protein associated with neutrophils used as a biomarker in the context of kidney injury.
Time frame
Measured before and after each treatment periodSecondary outcomes
1
Urine albumin/creatinin ratio (mg/g)
In spot urine samples, albumin and creatinin are measured
Time frame
Measured before (day one) and after (day 8) each treatment period2
Urine protein/creatinin ratio
In spot urine samples, albumin and creatinin are measured
Time frame
Measured before (day one) and after (day 8) each treatment period3
Home blood pressure (mmHg)
Home blood pressure are measured according to standard guidelines
Time frame
Measured before (day one) and after (day 8) each treatment periodSponsors and contacts
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Source ClinicalTrials.gov