Beneficial Effect of Amiloride on Progression of Chronic Kidney Disease

NCT06923709 | Recruiting Phase 2 DMC

• 2 other identifiers: EUCT: 2022-500692-31-002022-500692-31-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Kidney Disease(CKD); Proteinuria

Outcome Measures

Primary Outcomes (4)

• 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.

  Measured before (day one) and after (day 8) each treatment period

• 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.

  Measured before (day one) and after (day 8) each treatment period

• 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

  Measured before (day one) and after (day 8) each treatment period

• Neutrophil Gelatinase-Associated Lipocalin (NGAL) (pg/mL)

  NGAL is a protein associated with neutrophils used as a biomarker in the context of kidney injury.

  Measured before and after each treatment period

Secondary Outcomes (3)

• Urine albumin/creatinin ratio (mg/g)

  Measured before (day one) and after (day 8) each treatment period

• Urine protein/creatinin ratio

  Measured before (day one) and after (day 8) each treatment period

• Home blood pressure (mmHg)

  Measured before (day one) and after (day 8) each treatment period

Study Arms (2)

Amiloride

EXPERIMENTAL

Amiloride 5mg twice daily for 7 days followed by 2-3 weeks of washout and then placebo twice daily for 7 days

Drug: amiloride

Placebo

PLACEBO COMPARATOR

Placebo twice daily for 7 days followed by 2-3 weeks of washout and then Amilorid 5 mg twice daily for 7 days

Drug: Placebo

Interventions

amiloride DRUG

5mg twice daily for 7 days

Amiloride

Placebo DRUG

1 tablet twice daily for 7 days

Placebo

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study, only if all the following criteria apply:
• Participant must be 18 years of age including at the time of signing the informed consent.
• A clinical diagnosis of chronic kidney disease and:
• 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.
• Office blood pressure at screening meeting (visit 1), \> 110/60mmHg and \< 150/90mmHg. If BP \> 150/90mmHg at visit 1, screening phase can be prolonged to 4 weeks#.
• Capable of giving signed informed consent.
• Women with childbearing potential\* can only be included if a pregnancy test is negative at the screening visit. Moreover, women should be using contraception during the study.
• If the office blood pressure varies by approximately ±10 mmHg and is deemed acceptable by the investigator, the participant can be included.
• Women are considered of childbearing potential following menarche and until becoming post-menopausal (12 consecutive months without a menstrual period) unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy or bilateral oophorectomy (According to the Clinical Trial Facilitation Group, 2014-09-15).

You may not qualify if:

• Participants are excluded from the study is any of the following criteria apply:
• 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
• Evidence of current infection (CRP\> 50 and temperature \> 38◦C)
• History of unstable or rapidly progressing renal disease (eGFR decreasing \> 5ml/min/1.73m2 the last 2 months)
• Severe hepatic insufficiency classified as Child-Pugh C
• Patients on hypertension treatment who is not on stable antihypertensive treatment 2 weeks before start of study drug.
• Pregnancy or breastfeeding participants
• Congestive heart failure NYHA class IV, unstable or acute congestive heart failure.
• Recent cardiovascular events in a patient:
• Less than two months post coronary artery revascularization.
• Acute stroke or TIA within two months prior to screening
• Acute coronary syndrome within two months prior to screening

Sponsors & Collaborators

• Odense University Hospital: lead

Study Sites (1)

Department of Nephrology, Odense University Hospital

Odense, 5000, Denmark

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Proteinuria

Interventions

Amiloride

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; Urination Disorders; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Gitte Rye Hinrichs, MD, PhD

CONTACT

004521695186; gitte.rye.hinrichs2@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomized, double blinded, placebo controlled, crossover study

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 11, 2025
• Study Start: October 10, 2024
• Primary Completion: August 1, 2025
• Study Completion: November 1, 2025
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)