Effect of ACE-inhibitors on Aortic Stiffness in Elderly Patients With Chronic Kidney Disease

NCT ID: NCT00874432

Last Updated: 2020-10-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2011-12-31

Brief Summary

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The goal of this proposal is to investigate the potential for ACE-inhibitors (ACE-I)(drugs primarily used to treat hypertension or congestive heart failure) to prevent or delay cardiovascular disease (CVD) in older adults with chronic kidney disease (CKD) by examining their impact on aortic stiffness in people with stage 3 CKD in a randomized, controlled study.

Detailed Description

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This study will be the first to examine whether aortic stiffness is increased in elderly patients with CKD compared to their age-matched healthy controls and further examine whether ACE-I may delay the progression of aortic stiffness in elderly CKD patients. If ACE-I therapy appears beneficial in preventing or delaying arterial stiffening in elderly patients with CKD, this work has important implications for improving the overall health of this population.

Conditions

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Cardiovascular Disease Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Chronic Kidney Disease-ACE-I

ace inhibitor

Group Type ACTIVE_COMPARATOR

lisinopril

Intervention Type DRUG

1 x 40 mg per day

Chronic Kidney Disease

Group Type PLACEBO_COMPARATOR

angiotensin converting enzyme inhibitor

Intervention Type DRUG

Active comparator in chronic kidney disease and age matched control will take 1x40mg per day Placebo comparator in chronic kidney disease and age matched control will take 1 placebo pill per day

Age matched control-ACE-I

ace-inhibitor

Group Type ACTIVE_COMPARATOR

lisinopril

Intervention Type DRUG

1 x 40 mg per day

Age matched control

Placebo

Group Type PLACEBO_COMPARATOR

angiotensin converting enzyme inhibitor

Intervention Type DRUG

Active comparator in chronic kidney disease and age matched control will take 1x40mg per day Placebo comparator in chronic kidney disease and age matched control will take 1 placebo pill per day

Interventions

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angiotensin converting enzyme inhibitor

Active comparator in chronic kidney disease and age matched control will take 1x40mg per day Placebo comparator in chronic kidney disease and age matched control will take 1 placebo pill per day

Intervention Type DRUG

lisinopril

1 x 40 mg per day

Intervention Type DRUG

Other Intervention Names

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ACE-inhibitor ace inhibitor

Eligibility Criteria

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Inclusion Criteria

* Age \> 60 years
* BP 120/80 or higher \*(bps will be checked weekly first 4 weeks to ensure \< 130/80 - IF bp remains \> 130/80 we will administer other bp meds per JNC VII guidelines)
* CKD stage 3 (GFR 30 - 59 ml/min) for CKD group; no CKD for control group

Exclusion Criteria

* Known significant CVD (history of Myocardial infarction (MI), recurrent stroke, or New York Heart Association (NYHA) class III or greater).
* Serum potassium \> 5.2 meq/L
* Known allergy or hypersensitivity to ACE inhibitor or ARB
* Female of childbearing age not practicing contraception
* Current treatment with an Angiotensin Converting Enzyme Inhibitors (ACE-I) or Angiotensin-Receptor Blockers (ARB) (Note: can participate if on ACE-I after 6 week washout period)
* History of ACE-I induced angioedema
* History of angioedema, hereditary or idiopathic
* Persons lacking consent capacity

* 500 mg/dL proteinuria on 2 consecutive spot urine protein/creat ratios
Minimum Eligible Age

60 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arjang Djamali, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin-Madison School of Medicine and Public Health

Laura Maursetter, DO

Role: STUDY_DIRECTOR

University of Wisconsin, Madison

Locations

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University of Wisconsin-Madison Hospitals and Clinics

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Ryan TP, Sloand JA, Winters PC, Corsetti JP, Fisher SG. Chronic kidney disease prevalence and rate of diagnosis. Am J Med. 2007 Nov;120(11):981-6. doi: 10.1016/j.amjmed.2007.05.012.

Reference Type BACKGROUND
PMID: 17976426 (View on PubMed)

Foley RN, Parfrey PS. Cardiovascular disease and mortality in ESRD. J Nephrol. 1998 Sep-Oct;11(5):239-45.

Reference Type BACKGROUND
PMID: 9831236 (View on PubMed)

Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001 Oct;38(4):938-42. doi: 10.1161/hy1001.096358.

Reference Type BACKGROUND
PMID: 11641313 (View on PubMed)

Covic A, Haydar AA, Bhamra-Ariza P, Gusbeth-Tatomir P, Goldsmith DJ. Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients. J Nephrol. 2005 Jul-Aug;18(4):388-96.

Reference Type BACKGROUND
PMID: 16245242 (View on PubMed)

London GM, Marchais SJ, Guerin AP. Arterial stiffness and function in end-stage renal disease. Adv Chronic Kidney Dis. 2004 Apr;11(2):202-9. doi: 10.1053/j.arrt.2004.02.008.

Reference Type BACKGROUND
PMID: 15216492 (View on PubMed)

Wang MC, Tsai WC, Chen JY, Huang JJ. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am J Kidney Dis. 2005 Mar;45(3):494-501. doi: 10.1053/j.ajkd.2004.11.011.

Reference Type BACKGROUND
PMID: 15754271 (View on PubMed)

Kundhal K, Lok CE. Clinical epidemiology of cardiovascular disease in chronic kidney disease. Nephron Clin Pract. 2005;101(2):c47-52. doi: 10.1159/000086221. Epub 2005 Jun 7.

Reference Type BACKGROUND
PMID: 15942250 (View on PubMed)

Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, Jeppesen J. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006 Feb 7;113(5):664-70. doi: 10.1161/CIRCULATIONAHA.105.579342.

Reference Type BACKGROUND
PMID: 16461839 (View on PubMed)

London GM, Guerin AP, Marchais SJ, Pannier B, Safar ME, Day M, Metivier F. Cardiac and arterial interactions in end-stage renal disease. Kidney Int. 1996 Aug;50(2):600-8. doi: 10.1038/ki.1996.355.

Reference Type BACKGROUND
PMID: 8840292 (View on PubMed)

Shinohara K, Shoji T, Tsujimoto Y, Kimoto E, Tahara H, Koyama H, Emoto M, Ishimura E, Miki T, Tabata T, Nishizawa Y. Arterial stiffness in predialysis patients with uremia. Kidney Int. 2004 Mar;65(3):936-43. doi: 10.1111/j.1523-1755.2004.00468.x.

Reference Type BACKGROUND
PMID: 14871413 (View on PubMed)

Safar ME, London GM, Plante GE. Arterial stiffness and kidney function. Hypertension. 2004 Feb;43(2):163-8. doi: 10.1161/01.HYP.0000114571.75762.b0. Epub 2004 Jan 19.

Reference Type BACKGROUND
PMID: 14732732 (View on PubMed)

Dao HH, Essalihi R, Bouvet C, Moreau P. Evolution and modulation of age-related medial elastocalcinosis: impact on large artery stiffness and isolated systolic hypertension. Cardiovasc Res. 2005 May 1;66(2):307-17. doi: 10.1016/j.cardiores.2005.01.012.

Reference Type BACKGROUND
PMID: 15820199 (View on PubMed)

Ferrari AU, Radaelli A, Centola M. Invited review: aging and the cardiovascular system. J Appl Physiol (1985). 2003 Dec;95(6):2591-7. doi: 10.1152/japplphysiol.00601.2003.

Reference Type BACKGROUND
PMID: 14600164 (View on PubMed)

Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, Vasan RS, Levy D. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension. 2004 Jun;43(6):1239-45. doi: 10.1161/01.HYP.0000128420.01881.aa. Epub 2004 May 3.

Reference Type BACKGROUND
PMID: 15123572 (View on PubMed)

Sawabe M, Takahashi R, Matsushita S, Ozawa T, Arai T, Hamamatsu A, Nakahara K, Chida K, Yamanouchi H, Murayama S, Tanaka N. Aortic pulse wave velocity and the degree of atherosclerosis in the elderly: a pathological study based on 304 autopsy cases. Atherosclerosis. 2005 Apr;179(2):345-51. doi: 10.1016/j.atherosclerosis.2004.09.023. Epub 2004 Dec 13.

Reference Type BACKGROUND
PMID: 15777552 (View on PubMed)

London GM, Marchais SJ, Guerin AP, Pannier B. Arterial stiffness: pathophysiology and clinical impact. Clin Exp Hypertens. 2004 Oct-Nov;26(7-8):689-99. doi: 10.1081/ceh-200031982.

Reference Type BACKGROUND
PMID: 15702623 (View on PubMed)

London GM, Marchais SJ, Guerin AP, Metivier F. Arteriosclerosis, vascular calcifications and cardiovascular disease in uremia. Curr Opin Nephrol Hypertens. 2005 Nov;14(6):525-31. doi: 10.1097/01.mnh.0000168336.67499.c0.

Reference Type BACKGROUND
PMID: 16205470 (View on PubMed)

Touyz RM. The role of angiotensin II in regulating vascular structural and functional changes in hypertension. Curr Hypertens Rep. 2003 Apr;5(2):155-64. doi: 10.1007/s11906-003-0073-2.

Reference Type BACKGROUND
PMID: 12642016 (View on PubMed)

Unger T. Pharmacological properties of angiotensin II antagonists: examining all the therapeutic implications. J Renin Angiotensin Aldosterone Syst. 2001 Sep;2 Suppl 2:S4-7. doi: 10.3317/jraas.2001.030.

Reference Type BACKGROUND
PMID: 11881101 (View on PubMed)

Matsuda H, Hayashi K, Saruta T. Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease. J Hum Hypertens. 2003 Apr;17(4):271-6. doi: 10.1038/sj.jhh.1001543.

Reference Type BACKGROUND
PMID: 12692572 (View on PubMed)

Chrysant SG. Vascular remodeling: the role of angiotensin-converting enzyme inhibitors. Am Heart J. 1998 Feb;135(2 Pt 2):S21-30. doi: 10.1053/hj.1998.v135.86971.

Reference Type BACKGROUND
PMID: 9488609 (View on PubMed)

Bertrand ME. Provision of cardiovascular protection by ACE inhibitors: a review of recent trials. Curr Med Res Opin. 2004 Oct;20(10):1559-69. doi: 10.1185/030079904X4185.

Reference Type BACKGROUND
PMID: 15462689 (View on PubMed)

Fields LE, Burt VL, Cutler JA, Hughes J, Roccella EJ, Sorlie P. The burden of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension. 2004 Oct;44(4):398-404. doi: 10.1161/01.HYP.0000142248.54761.56. Epub 2004 Aug 23.

Reference Type BACKGROUND
PMID: 15326093 (View on PubMed)

Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D'Agostino RB, Levy D. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002 Feb 27;287(8):1003-10. doi: 10.1001/jama.287.8.1003.

Reference Type BACKGROUND
PMID: 11866648 (View on PubMed)

Franklin SS, Gustin W 4th, Wong ND, Larson MG, Weber MA, Kannel WB, Levy D. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation. 1997 Jul 1;96(1):308-15. doi: 10.1161/01.cir.96.1.308.

Reference Type BACKGROUND
PMID: 9236450 (View on PubMed)

Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005 Jul 27;294(4):466-72. doi: 10.1001/jama.294.4.466.

Reference Type BACKGROUND
PMID: 16046653 (View on PubMed)

Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998 Jun 13;351(9118):1755-62. doi: 10.1016/s0140-6736(98)04311-6.

Reference Type BACKGROUND
PMID: 9635947 (View on PubMed)

Darne B, Girerd X, Safar M, Cambien F, Guize L. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality. Hypertension. 1989 Apr;13(4):392-400. doi: 10.1161/01.hyp.13.4.392.

Reference Type BACKGROUND
PMID: 2522417 (View on PubMed)

Mitchell GF, Lacourciere Y, Ouellet JP, Izzo JL Jr, Neutel J, Kerwin LJ, Block AJ, Pfeffer MA. Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Circulation. 2003 Sep 30;108(13):1592-8. doi: 10.1161/01.CIR.0000093435.04334.1F. Epub 2003 Sep 15.

Reference Type BACKGROUND
PMID: 12975261 (View on PubMed)

Hallan S, Asberg A, Lindberg M, Johnsen H. Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. Am J Kidney Dis. 2004 Jul;44(1):84-93. doi: 10.1053/j.ajkd.2004.03.027.

Reference Type BACKGROUND
PMID: 15211442 (View on PubMed)

Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun;67(6):2089-100. doi: 10.1111/j.1523-1755.2005.00365.x.

Reference Type BACKGROUND
PMID: 15882252 (View on PubMed)

McEniery CM, Yasmin, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR; ACCT Investigators. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol. 2005 Nov 1;46(9):1753-60. doi: 10.1016/j.jacc.2005.07.037. Epub 2005 Oct 10.

Reference Type BACKGROUND
PMID: 16256881 (View on PubMed)

Mitchell GF, Izzo JL Jr, Lacourciere Y, Ouellet JP, Neutel J, Qian C, Kerwin LJ, Block AJ, Pfeffer MA. Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension: results of the conduit hemodynamics of omapatrilat international research study. Circulation. 2002 Jun 25;105(25):2955-61. doi: 10.1161/01.cir.0000020500.77568.3c.

Reference Type BACKGROUND
PMID: 12081987 (View on PubMed)

Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000 Mar 13;160(5):685-93. doi: 10.1001/archinte.160.5.685.

Reference Type BACKGROUND
PMID: 10724055 (View on PubMed)

Djamali A, Sadowski E, Muehrer R, et al. Losartan Improves Renal Medullary Oxygenation and Oxidative Stress in Patients with Chronic Allograft Nephropathy. J.Am.Soc.Nephrol. 15 (Abstract Issue):SA-PO1026, 2004

Reference Type BACKGROUND

Other Identifiers

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A534280

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH/MEDICINE/NEPHROLOGY

Identifier Type: OTHER

Identifier Source: secondary_id

H-2008-0221

Identifier Type: -

Identifier Source: org_study_id