A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
NCT ID: NCT02522650
Last Updated: 2020-02-07
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Clinical Phase
PHASE4
Total Enrollment
30 participants
Study Classification
INTERVENTIONAL
Study Start Date
2013-07-31
Study Completion Date
2021-10-31
Brief Summary
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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.
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Detailed Description
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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.
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.
Conditions
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Proteinuria
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
CROSSOVER
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Amiloride Phase
Subject receives 5mg of Amiloride twice daily for 8 weeks.
Group Type
EXPERIMENTAL
Amiloride
Intervention Type
DRUG
5mg twice a day for 8 weeks
Triamterene Phase
Subject receives 50mg of Triamterene twice daily for 8 weeks.
Group Type
ACTIVE_COMPARATOR
Triamterene
Intervention Type
DRUG
50mg twice a day for 8 weeks
Washout Phase
Subject does not take any study medication for 4 weeks
Group Type
NO_INTERVENTION
No interventions assigned to this group
Interventions
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Amiloride
5mg twice a day for 8 weeks
Intervention Type
DRUG
Triamterene
50mg twice a day for 8 weeks
Intervention Type
DRUG
Eligibility Criteria
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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
* 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
* 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
Minimum Eligible Age
18 Years
Maximum Eligible Age
75 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Georgetown University
OTHER
Sponsor Role
lead
Responsible Party
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Wen Shen, MD, PHD
Associate Professor of Medicine
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Wen Shen, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Georgetown University Hospital
Locations
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Georgetown University
Washington D.C., District of Columbia, United States
Site Status
RECRUITING
Countries
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United States
Central Contacts
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Facility Contacts
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MD
Role: backup
202-444-1089
References
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BACKGROUND
Shen W, Alshehri M, Desale S, Wilcox C. The Effect of Amiloride on Proteinuria in Patients with Proteinuric Kidney Disease. Am J Nephrol. 2021;52(5):368-377. doi: 10.1159/000515809. Epub 2021 May 6.
Reference Type
DERIVED
Other Identifiers
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2013-0496
Identifier Type: -
Identifier Source: org_study_id
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