A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

Sponsor

Georgetown University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02522650

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Jul 1, 2013

Anticipated Primary Completion Date :

Oct 1, 2021

Anticipated Study Completion Date :

Oct 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

24 hr urine protein excretion [20 weeks]
Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.

Secondary Outcome Measures

urine plasmin activity [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 [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 [20 weeks]
examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.
serum suPAR concentration [20 weeks]
examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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