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A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

Information source: Georgetown University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Proteinuria

Intervention: Amiloride (Drug); Triamterene (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Georgetown University

Official(s) and/or principal investigator(s):
Wen Shen, MD, PhD, Principal Investigator, Affiliation: Georgetown University Hospital

Overall contact:
Stephanie Gubb, Phone: 202-444-1210, Email: smg256@georgetown.edu

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 24 hr urine protein excretion

Secondary outcome:

urine plasmin activity

urine plasminogen activity

urine suPAR concentration

serum suPAR concentration

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.

Eligibility

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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

Locations and Contacts

Stephanie Gubb, Phone: 202-444-1210, Email: smg256@georgetown.edu

Georgetown University, Washington, District of Columbia 20007, United States; Recruiting
Stephanie Gubb, Phone: 202-444-1210, Email: smg256@georgetown.edu
Rodrigo Aguilar, MD, Phone: 202-444-1089, Email: fra26@georgetown.edu
Wen Shen, MD, PhD, Principal Investigator
Additional Information

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Starting date: July 2013
Last updated: August 11, 2015

Page last updated: August 23, 2015

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