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History of Changes for Study: NCT02522650
A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
Latest version (submitted February 6, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 11, 2015 None (earliest Version on record)
2 November 18, 2016 Study Status
3 October 12, 2017 Contacts/Locations and Study Status
4 January 17, 2019 Study Status, Contacts/Locations and Sponsor/Collaborators
5 February 6, 2020 Study Status
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Study NCT02522650
Submitted Date:  October 12, 2017 (v3)

Open or close this module Study Identification
Unique Protocol ID: 2013-0496
Brief Title: 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
Secondary IDs:
Open or close this module Study Status
Record Verification: October 2017
Overall Status: Recruiting
Study Start: July 2013
Primary Completion: October 2019 [Anticipated]
Study Completion: October 2019 [Anticipated]
First Submitted: July 23, 2015
First Submitted that
Met QC Criteria:
August 11, 2015
First Posted: August 13, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
October 12, 2017
Last Update Posted: October 13, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Georgetown University
Responsible Party: Principal Investigator
Investigator: Wen Shen, MD, PHD
Official Title: Assistant Professor of Medicine
Affiliation: Georgetown University
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module 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.
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.

Open or close this module Conditions
Conditions: Proteinuria
Keywords: amiloride
proteinuric kidney disease
urokinase plasminogen activator receptor
proteinuria
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 4
Interventional Study Model: Crossover Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 24 hr urine protein excretion
Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.

[Time Frame: 20 weeks]
Secondary Outcome Measures:
2. 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.

[Time Frame: 20 weeks]
3. urine plasminogen activity
examine urine plasminogen activity during the 3 phases of the study. urine plasminogen will be measured by gelatin-PAGE zymography.

[Time Frame: 20 weeks]
4. urine suPAR concentration
examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.

[Time Frame: 20 weeks]
5. serum suPAR concentration
examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.

[Time Frame: 20 weeks]
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Central Contact Person: Margie Dimatulac
Telephone: 202-444-1210
Email: mcd136@georgetown.edu
Study Officials: Wen Shen, MD, PhD
Principal Investigator
Georgetown University Hospital
Locations: United States, District of Columbia
Georgetown University
[Recruiting]
Washington, D.C., District of Columbia, United States, 20007
Contact:Contact: Margie Dimatulac 202-444-1210 mcd136@georgetown.edu.edu
Contact:Contact: MD 202-444-1089
Contact:Principal Investigator: Wen Shen, MD, PhD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations: Berhane AM, Weil EJ, Knowler WC, Nelson RG, Hanson RL. Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death. Clin J Am Soc Nephrol. 2011 Oct;6(10):2444-51. doi: 10.2215/CJN.00580111. Epub 2011 Aug 18. PubMed 21852671
Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002 Dec;3(12):932-43. Review. PubMed 12461559
Brown EA, Markandu ND, Roulston JE, Jones BE, Squires M, MacGregor GA. Is the renin-angiotensin-aldosterone system involved in the sodium retention in the nephrotic syndrome? Nephron. 1982;32(2):102-7. PubMed 6757778
Brown EA, Markandu ND, Sagnella GA, Jones BE, MacGregor GA. Lack of effect of captopril on the sodium retention of the nephrotic syndrome. Nephron. 1984;37(1):43-8. PubMed 6371561
Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F. Blockade of epithelial Na+ channels by triamterenes - underlying mechanisms and molecular basis. Pflugers Arch. 1996 Sep;432(5):760-6. PubMed 8772124
Geers AB, Koomans HA, Roos JC, Boer P, Dorhout Mees EJ. Functional relationships in the nephrotic syndrome. Kidney Int. 1984 Sep;26(3):324-30. PubMed 6392692
Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997 Jun 28;349(9069):1857-63. PubMed 9217756
Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M; Alberta Kidney Disease Network. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010 Feb 3;303(5):423-9. doi: 10.1001/jama.2010.39. PubMed 20124537
Iishi H, Tatsuta M, Baba M, Yano H, Uehara H, Nakaizumi A. Suppression by amiloride of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane. Int J Cancer. 1995 Nov 27;63(5):716-9. PubMed 7591290
Kellen JA, Mirakian A, Kolin A. Antimetastatic effect of amiloride in an animal tumour model. Anticancer Res. 1988 Nov-Dec;8(6):1373-6. PubMed 3218971
Laurens WE, Vanrenterghem YF, Steels PS, Van Damme BJ. A new single nephron model of focal and segmental glomerulosclerosis in the Munich-Wistar rat. Kidney Int. 1994 Jan;45(1):143-9. PubMed 8127003
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993 Nov 11;329(20):1456-62. Erratum in: N Engl J Med 1993 Jan 13;330(2):152. PubMed 8413456
Madsen CD, Ferraris GM, Andolfo A, Cunningham O, Sidenius N. uPAR-induced cell adhesion and migration: vitronectin provides the key. J Cell Biol. 2007 Jun 4;177(5):927-39. PubMed 17548516
Mathieson PW. Proteinuria and immunity--an overstated relationship? N Engl J Med. 2008 Dec 4;359(23):2492-4. doi: 10.1056/NEJMcibr0806881. PubMed 19052132
Meltzer JI, Keim HJ, Laragh JH, Sealey JE, Jan KM, Chien S. Nephrotic syndrome: vasoconstriction and hypervolemic types indicated by renin-sodium profiling. Ann Intern Med. 1979 Nov;91(5):688-96. PubMed 496101
Reiser J, Oh J, Shirato I, Asanuma K, Hug A, Mundel TM, Honey K, Ishidoh K, Kominami E, Kreidberg JA, Tomino Y, Mundel P. Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin. J Biol Chem. 2004 Aug 13;279(33):34827-32. Epub 2004 Jun 14. PubMed 15197181
Rennke HG. How does glomerular epithelial cell injury contribute to progressive glomerular damage? Kidney Int Suppl. 1994 Feb;45:S58-63. Review. PubMed 8158900
Sepehrdad R, Chander PN, Oruene A, Rosenfeld L, Levine S, Stier CT Jr. Amiloride reduces stroke and renalinjury in stroke-prone hypertensive rats. Am J Hypertens. 2003 Apr;16(4):312-8. PubMed 12670749
Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers. 2009;27(3):157-72. doi: 10.3233/DMA-2009-0657. Review. PubMed 19893210
Trivedi S, Zeier M, Reiser J. Role of podocytes in lupus nephritis. Nephrol Dial Transplant. 2009 Dec;24(12):3607-12. doi: 10.1093/ndt/gfp427. Epub 2009 Sep 3. Review. PubMed 19729466
Usberti M, Federico S, Meccariello S, Cianciaruso B, Balletta M, Pecoraro C, Sacca L, Ungaro B, Pisanti N, Andreucci VE. Role of plasma vasopressin in the impairment of water excretion in nephrotic syndrome. Kidney Int. 1984 Feb;25(2):422-9. PubMed 6727137
Vande Walle J, Donckerwolcke R, Boer P, van Isselt HW, Koomans HA, Joles JA. Blood volume, colloid osmotic pressure and F-cell ratio in children with the nephrotic syndrome. Kidney Int. 1996 May;49(5):1471-7. PubMed 8731116
Vande Walle JG, Donckerwolcke RA, Koomans HA. Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease. J Am Soc Nephrol. 1999 Feb;10(2):323-31. PubMed 10215332
Wang Y, Jones CJ, Dang J, Liang X, Olsen JE, Doe WF. Human urokinase receptor expression is inhibited by amiloride and induced by tumor necrosis factor and phorbol ester in colon cancer cells. FEBS Lett. 1994 Oct 17;353(2):138-42. PubMed 7926038
Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J, Maiguel D, Karumanchi SA, Yap HK, Saleem M, Zhang Q, Nikolic B, Chaudhuri A, Daftarian P, Salido E, Torres A, Salifu M, Sarwal MM, Schaefer F, Morath C, Schwenger V, Zeier M, Gupta V, Roth D, Rastaldi MP, Burke G, Ruiz P, Reiser J. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. 2011 Jul 31;17(8):952-60. doi: 10.1038/nm.2411. PubMed 21804539
Wei C, Möller CC, Altintas MM, Li J, Schwarz K, Zacchigna S, Xie L, Henger A, Schmid H, Rastaldi MP, Cowan P, Kretzler M, Parrilla R, Bendayan M, Gupta V, Nikolic B, Kalluri R, Carmeliet P, Mundel P, Reiser J. Modification of kidney barrier function by the urokinase receptor. Nat Med. 2008 Jan;14(1):55-63. Epub 2007 Dec 16. PubMed 18084301
Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ, McMahan JL, Radeva M, Heil KM, Trautmann A, Anarat A, Emre S, Ghiggeri GM, Ozaltin F, Haffner D, Gipson DS, Kaskel F, Fischer DC, Schaefer F, Reiser J; PodoNet and FSGS CT Study Consortia. Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol. 2012 Dec;23(12):2051-9. doi: 10.1681/ASN.2012030302. Epub 2012 Nov 8. PubMed 23138488
Wei Y, Waltz DA, Rao N, Drummond RJ, Rosenberg S, Chapman HA. Identification of the urokinase receptor as an adhesion receptor for vitronectin. J Biol Chem. 1994 Dec 23;269(51):32380-8. PubMed 7528215
Wu S, Murrell GA, Wang Y. Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression. Cancer Immunol Immunother. 2002 Jul;51(5):248-54. Epub 2002 Apr 9. PubMed 12070711
Zhang B, Xie S, Shi W, Yang Y. Amiloride off-target effect inhibits podocyte urokinase receptor expression and reduces proteinuria. Nephrol Dial Transplant. 2012 May;27(5):1746-55. doi: 10.1093/ndt/gfr612. Epub 2011 Nov 9. PubMed 22076430
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