Clinical trial NCT02522650: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Proteinuria
Keywords: amiloride
proteinuric kidney disease
urokinase plasminogen activator receptor
proteinuria
Lead sponsor: Georgetown University
Sponsor class: OTHER
First posted: 2015-08-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 24 hr urine protein excretion
timeFrame: 20 weeks
Secondary outcomes:
measure: urine plasmin activity
timeFrame: 20 weeks
measure: urine plasminogen activity
timeFrame: 20 weeks
measure: urine suPAR concentration
timeFrame: 20 weeks
measure: serum suPAR concentration
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
Study officials:
affiliation: Georgetown University Hospital
name: Wen Shen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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