Ignite Creation Date:
2025-12-24 @ 5:03 PM
Ignite Modification Date:
2026-02-19 @ 2:39 PM
Study NCT ID:
NCT02522650
Status:
UNKNOWN
Last Update Posted:
2020-02-07
First Post:
2015-07-23
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011507', 'term': 'Proteinuria'}], 'ancestors': [{'id': 'D014555', 'term': 'Urination Disorders'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D020924', 'term': 'Urological Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000584', 'term': 'Amiloride'}, {'id': 'D014223', 'term': 'Triamterene'}], 'ancestors': [{'id': 'D011719', 'term': 'Pyrazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2013-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-02', 'completionDateStruct': {'date': '2021-10', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-02-06', 'studyFirstSubmitDate': '2015-07-23', 'studyFirstSubmitQcDate': '2015-08-11', 'lastUpdatePostDateStruct': {'date': '2020-02-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-08-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2021-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '24 hr urine protein excretion', 'timeFrame': '20 weeks', 'description': 'Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.'}], 'secondaryOutcomes': [{'measure': 'urine plasmin activity', 'timeFrame': '20 weeks', 'description': 'examine urine plasmin activity during the 3 phases of the study. Serum and urine plasmin will be measured by gelatin-PAGE zymography.'}, {'measure': 'urine plasminogen activity', 'timeFrame': '20 weeks', 'description': 'examine urine plasminogen activity during the 3 phases of the study. urine plasminogen will be measured by gelatin-PAGE zymography.'}, {'measure': 'urine suPAR concentration', 'timeFrame': '20 weeks', 'description': 'examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.'}, {'measure': 'serum suPAR concentration', 'timeFrame': '20 weeks', 'description': 'examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['amiloride', 'proteinuric kidney disease', 'urokinase plasminogen activator receptor', 'proteinuria'], 'conditions': ['Proteinuria']}, 'referencesModule': {'references': [{'pmid': '21852671', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '12461559', 'type': 'BACKGROUND', 'citation': 'Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002 Dec;3(12):932-43. doi: 10.1038/nrm977.'}, {'pmid': '6757778', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1159/000182827.'}, {'pmid': '6371561', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1159/000183206.'}, {'pmid': '8772124', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1007/s004240050196.'}, {'pmid': '6392692', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1038/ki.1984.176.'}, {'pmid': '9217756', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '20124537', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '7591290', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1002/ijc.2910630518.'}, {'pmid': '3218971', 'type': 'BACKGROUND', 'citation': 'Kellen JA, Mirakian A, Kolin A. Antimetastatic effect of amiloride in an animal tumour model. Anticancer Res. 1988 Nov-Dec;8(6):1373-6.'}, {'pmid': '8127003', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1038/ki.1994.17.'}, {'pmid': '8413456', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1056/NEJM199311113292004.'}, {'pmid': '17548516', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1083/jcb.200612058.'}, {'pmid': '19052132', 'type': 'BACKGROUND', 'citation': 'Mathieson PW. Proteinuria and immunity--an overstated relationship? N Engl J Med. 2008 Dec 4;359(23):2492-4. doi: 10.1056/NEJMcibr0806881. No abstract available.'}, {'pmid': '496101', 'type': 'BACKGROUND', 'citation': '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. doi: 10.7326/0003-4819-91-5-688.'}, {'pmid': '15197181', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1074/jbc.M401973200. Epub 2004 Jun 14.'}, {'pmid': '8158900', 'type': 'BACKGROUND', 'citation': 'Rennke HG. How does glomerular epithelial cell injury contribute to progressive glomerular damage? Kidney Int Suppl. 1994 Feb;45:S58-63.'}, {'pmid': '12670749', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1016/s0895-7061(03)00006-2.'}, {'pmid': '19893210', 'type': 'BACKGROUND', 'citation': 'Thuno M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers. 2009;27(3):157-72. doi: 10.3233/DMA-2009-0657.'}, {'pmid': '19729466', 'type': 'BACKGROUND', 'citation': '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. No abstract available.'}, {'pmid': '6727137', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1038/ki.1984.34.'}, {'pmid': '8731116', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1038/ki.1996.207. No abstract available.'}, {'pmid': '10215332', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1681/ASN.V102323.'}, {'pmid': '7926038', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1016/0014-5793(94)01032-3.'}, {'pmid': '21804539', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '18084301', 'type': 'BACKGROUND', 'citation': 'Wei C, Moller 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. doi: 10.1038/nm1696. Epub 2007 Dec 16.'}, {'pmid': '23138488', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '7528215', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '12070711', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1007/s00262-002-0275-5. Epub 2002 Apr 9.'}, {'pmid': '22076430', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '33957621', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nSpecific Aim 1: To examine the effects of amiloride on 24 hour urine protein excretion in patients with proteinuric kidney diseases.\n\nSpecific Aim 2: To study if the effect of amiloride on proteinuria reduction is mediated by suppressing soluble urokinase plasminogen activator receptor (suPAR) expression.\n\nStudy Design:\n\nThe 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.\n\nPhase 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.\n\nPhase 2: the patients will discontinue amiloride or triamterene for a washout for 4 weeks, but continue with the ACE inhibitor or ARB.\n\nPhase 3: the patients will cross over to triamterene or amiloride for 8 weeks. Use the protocol as described in phase 1.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patient with any type of proteinuric kidney diseases\n* Aged 18-75\n* Proteinuria ≥1g/day\n* estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m2\n\nExclusion Criteria:\n\n* Clinical evidences of lupus nephritis, or HIV associated nephropathy\n* eGFR \\<30ml/min/1.73m2\n* Requirement for treatment with mineralocorticoid receptor antagonists (spironolactone, eplerenone)\n* Status post kidney transplant\n* Received glucocorticoid steroids within six months\n* Serum K \\>4.8 mmol/L\n* Total carbon dioxide \\<17 mmol/L\n* Hemoglobin \\<10 g/dl\n* Contraindicated or allergic to loop diuretics or potassium sparing diuretics\n* Abnormal liver function tests'}, 'identificationModule': {'nctId': 'NCT02522650', 'briefTitle': 'A Crossover Pilot Study of the Effect of Amiloride on Proteinuria', 'organization': {'class': 'OTHER', 'fullName': 'Georgetown University'}, 'officialTitle': 'A Crossover Pilot Study of the Effect of Amiloride on Proteinuria in Patients With Proteinuric Kidney Disease', 'orgStudyIdInfo': {'id': '2013-0496'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Amiloride Phase', 'description': 'Subject receives 5mg of Amiloride twice daily for 8 weeks.', 'interventionNames': ['Drug: Amiloride']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Triamterene Phase', 'description': 'Subject receives 50mg of Triamterene twice daily for 8 weeks.', 'interventionNames': ['Drug: Triamterene']}, {'type': 'NO_INTERVENTION', 'label': 'Washout Phase', 'description': 'Subject does not take any study medication for 4 weeks'}], 'interventions': [{'name': 'Amiloride', 'type': 'DRUG', 'description': '5mg twice a day for 8 weeks', 'armGroupLabels': ['Amiloride Phase']}, {'name': 'Triamterene', 'type': 'DRUG', 'description': '50mg twice a day for 8 weeks', 'armGroupLabels': ['Triamterene Phase']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20007', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Margie Dimatulac', 'role': 'CONTACT', 'email': 'mcd136@georgetown.edu.edu', 'phone': '202-444-1210'}, {'name': 'MD', 'role': 'CONTACT', 'phone': '202-444-1089'}, {'name': 'Wen Shen, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Georgetown University', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}], 'centralContacts': [{'name': 'Margie Dimatulac', 'role': 'CONTACT', 'email': 'mcd136@georgetown.edu', 'phone': '202-444-1210'}], 'overallOfficials': [{'name': 'Wen Shen, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Georgetown University Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Georgetown University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Medicine', 'investigatorFullName': 'Wen Shen, MD, PHD', 'investigatorAffiliation': 'Georgetown University'}}}}