Clinical Trial: A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 Summary:

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 potassi
Sponsor: Georgetown University

Current Primary Outcome: 24 hr urine protein excretion [ Time Frame: 20 weeks ]

Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.


Original Secondary Outcome: Same as current

Information By: Georgetown University

Dates:
Date Received: July 23, 2015
Date Started: July 2013
Date Completion: October 2017
Last Updated: November 18, 2016
Last Verified: November 2016