A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

February 6, 2020 updated by: Wen Shen, MD, PHD, Georgetown University

A Crossover Pilot Study of the Effect of Amiloride on Proteinuria in Patients With Proteinuric Kidney Disease

This cross-over study is designed to test the hypothesis that amiloride will reduce urinary protein excretion and protect the kidney from rapid progression in proteinuric kidney disease.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Patients with proteinuric kidney disease will be enrolled and receive either amiloride or triamterene first, a similar diuretic acting on epithelial sodium channel (ENaC) as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then patients will cross over to receive another medication. We postulate that amiloride could be beneficial in the patients with proteinuric kidney diseases and could be used as an adjunct therapy to reduce proteinuria and to delay renal disease progression in this patient population.

Specific Aim 1: To examine the effects of amiloride on 24 hour urine protein excretion in patients with proteinuric kidney diseases.

Specific Aim 2: To study if the effect of amiloride on proteinuria reduction is mediated by suppressing soluble urokinase plasminogen activator receptor (suPAR) expression.

Study Design:

The study includes 3 phases. 30 patients will be recruited to this study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least two month prior to the study.

Phase 1: Patients will be randomized to receive either amiloride 5mg twice daily or triamterene 50mg twice daily for 8 weeks. Serum potassium will be monitored one week before and one week after starting phase 1. If serum potassium remains equal to or less than 5.0mmol/L, amiloride or triamterene will be continued at same dose until the end of phase 1. If serum potassium is equal to or above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium is between 5.1-5.4 mmol/L, it will be monitored again in one week. If serum potassium is above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium remains in the same range, the patient will continue amiloride or triamterene at the same dose to complete phase 1.

Phase 2: the patients will discontinue amiloride or triamterene for a washout for 4 weeks, but continue with the ACE inhibitor or ARB.

Phase 3: the patients will cross over to triamterene or amiloride for 8 weeks. Use the protocol as described in phase 1.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University
        • Contact:
        • Contact:
          • MD
          • Phone Number: 202-444-1089
        • Principal Investigator:
          • Wen Shen, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient with any type of proteinuric kidney diseases
  • Aged 18-75
  • Proteinuria ≥1g/day
  • estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m2

Exclusion Criteria:

  • Clinical evidences of lupus nephritis, or HIV associated nephropathy
  • eGFR <30ml/min/1.73m2
  • Requirement for treatment with mineralocorticoid receptor antagonists (spironolactone, eplerenone)
  • Status post kidney transplant
  • Received glucocorticoid steroids within six months
  • Serum K >4.8 mmol/L
  • Total carbon dioxide <17 mmol/L
  • Hemoglobin <10 g/dl
  • Contraindicated or allergic to loop diuretics or potassium sparing diuretics
  • Abnormal liver function tests

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Amiloride Phase
Subject receives 5mg of Amiloride twice daily for 8 weeks.
Drug: Amiloride
5mg twice a day for 8 weeks
Active Comparator: Triamterene Phase
Subject receives 50mg of Triamterene twice daily for 8 weeks.
Drug: Triamterene
50mg twice a day for 8 weeks
No Intervention: Washout Phase
Subject does not take any study medication for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24 hr urine protein excretion
Time Frame: 20 weeks
Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.
20 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
urine plasmin activity
Time Frame: 20 weeks
examine urine plasmin activity during the 3 phases of the study. Serum and urine plasmin will be measured by gelatin-PAGE zymography.
20 weeks
urine plasminogen activity
Time Frame: 20 weeks
examine urine plasminogen activity during the 3 phases of the study. urine plasminogen will be measured by gelatin-PAGE zymography.
20 weeks
urine suPAR concentration
Time Frame: 20 weeks
examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.
20 weeks
serum suPAR concentration
Time Frame: 20 weeks
examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.
20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Investigators

  • Principal Investigator: Wen Shen, MD, PhD, Georgetown University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (Anticipated)

October 1, 2021

Study Completion (Anticipated)

October 1, 2021

Study Registration Dates

First Submitted

July 23, 2015

First Submitted That Met QC Criteria

August 11, 2015

First Posted (Estimate)

August 13, 2015

Study Record Updates

Last Update Posted (Actual)

February 7, 2020

Last Update Submitted That Met QC Criteria

February 6, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-0496

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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