A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

Georgetown University

Status and phase: Unknown; Phase 4

Conditions: Proteinuria

Treatments: Drug: Amiloride; Drug: Triamterene

Study type: Interventional

Funder types: Other

Identifiers

NCT02522650

2013-0496

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Amiloride Phase

Experimental group

Description:

Subject receives 5mg of Amiloride twice daily for 8 weeks.

Treatment:

Drug: Amiloride

Triamterene Phase

Active Comparator group

Description:

Subject receives 50mg of Triamterene twice daily for 8 weeks.

Treatment:

Drug: Triamterene

Washout Phase

No Intervention group

Description:

Subject does not take any study medication for 4 weeks