History of Changes for Study: NCT02522650
A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
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Study Record Versions
Version A B Submitted Date Changes
1 August 11, 2015 None (earliest Version on record)
2 November 18, 2016 Study Status
3 October 12, 2017 Contacts/Locations and Study Status
4 January 17, 2019 Study Status, Contacts/Locations and Sponsor/Collaborators
5 February 6, 2020 Study Status
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Study NCT02522650
Submitted Date:  October 12, 2017 (v3)

Open or close this module Study Identification
Unique Protocol ID: 2013-0496
Brief Title: A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
Official Title: A Crossover Pilot Study of the Effect of Amiloride on Proteinuria in Patients With Proteinuric Kidney Disease
Secondary IDs:
Open or close this module Study Status
Record Verification: October 2017
Overall Status: Recruiting
Study Start: July 2013
Primary Completion: October 2019 [Anticipated]
Study Completion: October 2019 [Anticipated]
First Submitted: July 23, 2015
First Submitted that
Met QC Criteria:
August 11, 2015
First Posted: August 13, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
October 12, 2017
Last Update Posted: October 13, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Georgetown University
Responsible Party: Principal Investigator
Investigator: Wen Shen, MD, PHD
Official Title: Assistant Professor of Medicine
Affiliation: Georgetown University
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: 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.
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.

Open or close this module Conditions
Conditions: Proteinuria
Keywords: amiloride
proteinuric kidney disease
urokinase plasminogen activator receptor
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 4
Interventional Study Model: Crossover Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 24 hr urine protein excretion
Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.

[Time Frame: 20 weeks]
Secondary Outcome Measures:
2. urine plasmin activity
examine urine plasmin activity during the 3 phases of the study. Serum and urine plasmin will be measured by gelatin-PAGE zymography.

[Time Frame: 20 weeks]
3. urine plasminogen activity
examine urine plasminogen activity during the 3 phases of the study. urine plasminogen will be measured by gelatin-PAGE zymography.

[Time Frame: 20 weeks]
4. urine suPAR concentration
examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.

[Time Frame: 20 weeks]
5. serum suPAR concentration
examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.

[Time Frame: 20 weeks]
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No

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
Open or close this module Contacts/Locations
Central Contact Person: Margie Dimatulac
Telephone: 202-444-1210
Study Officials: Wen Shen, MD, PhD
Principal Investigator
Georgetown University Hospital
Locations: United States, District of Columbia
Georgetown University
Washington, D.C., District of Columbia, United States, 20007
Contact:Contact: Margie Dimatulac 202-444-1210
Contact:Contact: MD 202-444-1089
Contact:Principal Investigator: Wen Shen, MD, PhD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
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