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A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

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ClinicalTrials.gov Identifier: NCT02522650
Recruitment Status : Recruiting
First Posted : August 13, 2015
Last Update Posted : February 7, 2020
Sponsor:
Information provided by (Responsible Party):
Wen Shen, MD, PHD, Georgetown University

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.

Condition or disease Intervention/treatment Phase
Proteinuria Drug: Amiloride Drug: Triamterene Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Crossover Pilot Study of the Effect of Amiloride on Proteinuria in Patients With Proteinuric Kidney Disease
Study Start Date : July 2013
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 24 hr urine protein excretion [ Time Frame: 20 weeks ]
    Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02522650


Contacts
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Contact: Margie Dimatulac 202-444-1210 mcd136@georgetown.edu

Locations
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United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Margie Dimatulac    202-444-1210    mcd136@georgetown.edu.edu   
Contact: MD    202-444-1089      
Principal Investigator: Wen Shen, MD, PhD         
Sponsors and Collaborators
Georgetown University
Investigators
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Principal Investigator: Wen Shen, MD, PhD Georgetown University Hospital
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Wen Shen, MD, PHD, Associate Professor of Medicine, Georgetown University
ClinicalTrials.gov Identifier: NCT02522650    
Other Study ID Numbers: 2013-0496
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 2020
Keywords provided by Wen Shen, MD, PHD, Georgetown University:
amiloride
proteinuric kidney disease
urokinase plasminogen activator receptor
proteinuria
Additional relevant MeSH terms:
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Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Amiloride
Triamterene
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing