A Crossover Pilot Study of the Effect of Amiloride on Proteinuria

Proteinuria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02522650
• Other study ID #: 2013-0496
• Status: Recruiting
• Phase: Phase 4
• Start date: July 2013
• Est. completion date: October 2021

Study information

• Verified date: February 2020
• Source: Georgetown University
• Contact: Margie Dimatulac
• Phone: 202-444-1210
• Email: mcd136[@]georgetown.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Proteinuria

Intervention

Drug:
• Amiloride
5mg twice a day for 8 weeks
• Triamterene
50mg twice a day for 8 weeks

Locations

Country	Name	City	State
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Georgetown University

Country where clinical trial is conducted

United States, 

References & Publications (30)

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24 hr urine protein excretion	Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.	20 weeks
Secondary	urine plasmin activity	examine urine plasmin activity during the 3 phases of the study. Serum and urine plasmin will be measured by gelatin-PAGE zymography.	20 weeks
Secondary	urine plasminogen activity	examine urine plasminogen activity during the 3 phases of the study. urine plasminogen will be measured by gelatin-PAGE zymography.	20 weeks
Secondary	urine suPAR concentration	examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.	20 weeks
Secondary	serum suPAR concentration	examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.	20 weeks