Effect of Pravastatin on Erythrocyte Membrane Fatty Acid Contents in Patients With Chronic Kidney Disease

NCT ID: NCT02992548

Last Updated: 2019-03-11

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

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2018-12-31

Brief Summary

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Treatment using statin has been decreased the risk of cardiovascular events in pre-dialysis CKD population. Supplementation with omega-3 fatty acid (FA) lowers the risk of cardiovascular death in patients with myocardial infarction. This cardioprotective effect of omega-3 FA can be explained by anti-inflammatory, anti-oxidative, or anti-thrombotic effects. Statin such as pravastatin is also known to have anti-inflammatory and antioxidant properties, suggesting that statin may replace the cardioprotective effect of omega-3 fatty acids. Erythrocyte membrane oleic acid is significantly higher in patients with acute coronary syndrome than control subjects. The cardioprotective effect of omega-3 FA may also be related to decreased oleic acid content of erythrocyte membrane. There is no report about the effect of statin on FA including erythrocyte membrane oleic acid. As omega-3 FAs are recognized as therapeutic agents for reducing triglycerides, statin may affect on the erythrocyte membrane FA. Therefore, pravastatin supplementation can modify erythrocyte membrane FA contents including oleic acid in CKD patients.

Detailed Description

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Patients with chronic kidney disease (CKD) have higher risk of death and cardiovascular disease than general population. Treatment using statin has been decreased the risk of cardiovascular events in pre-dialysis CKD population. Supplementation with omega-3 fatty acid (FA) lowers the risk of cardiovascular death in patients with myocardial infarction. This cardioprotective effect of omega-3 FA can be explained by anti-inflammatory, anti-oxidative, or anti-thrombotic effects. Statin such as pravastatin is also known to have anti-inflammatory and antioxidant properties, suggesting that statin may replace the cardioprotective effect of omega-3 fatty acids.

Omega-3 FA such as EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and EPA/arachidonic acid ratio are well known as key indicators of cardiovascular disease. In addition, erythrocyte membrane oleic acid is significantly higher in patients with acute coronary syndrome than control subjects. The cardioprotective effect of omega-3 FA may also be related to decreased oleic acid content of erythrocyte membrane. There is no report about the effect of statin on FA including erythrocyte membrane oleic acid. As omega-3 FAs are recognized as therapeutic agents for reducing triglycerides, statin may affect on the erythrocyte membrane FA. Therefore, pravastatin supplementation can modify erythrocyte membrane FA contents including oleic acid in CKD patients.

Conditions

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Chronic Kidney Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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pravastatin group

Use of pravastatin 20mg to 40mg

Group Type EXPERIMENTAL

Pravastatin

Intervention Type DRUG

Interventions

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Pravastatin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* CKD patients who agreed with written informed consent
* CKD patients who do not take statin
* Who have LDL cholesterol over 100mg/dL and coronary vascular disease(CVD) or equivalent risk; Who have LDL cholesterol over 130mg/dL and two or more coronary vascular risk; Whose LDL cholesterol over 160mg/dL in patient with CKD stage 1 to 5 without dialysis.

Exclusion Criteria

* Patients with acute illness, a history of active infection, CVD, acute kidney injury during the past 3 months, or a history of malignancy or liver disease
* Patients using statin, omega-3 fatty acid or sevelamer hydrochloride within 3 months
* Patients who experienced side effects by statin treatment
* Pregnant or pregnancy expected CKD patients
* Patient with dyslipidemia due to nephrotic syndrome
* Patient taken imaging study using contrast media during the past 14 days
* Patient with albumin level \< 3.0 g/dL
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dong-A University

OTHER

Sponsor Role lead

Responsible Party

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WON SUK AN

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Won Suk An, MD

Role: PRINCIPAL_INVESTIGATOR

Dong-A University

Yeong Hoon Kim, MD

Role: STUDY_DIRECTOR

Inje University

Locations

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Dong-A University

Busan, , South Korea

Site Status

Inje University, Pusan Paik Hospital

Busan, , South Korea

Site Status

Countries

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South Korea

References

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Tonelli M, Muntner P, Lloyd A, Manns B, Klarenbach S, Pannu N, James M, Hemmelgarn B; Alberta Kidney Disease Network. Association between LDL-C and risk of myocardial infarction in CKD. J Am Soc Nephrol. 2013 May;24(6):979-86. doi: 10.1681/ASN.2012080870. Epub 2013 May 16.

Reference Type BACKGROUND
PMID: 23687359 (View on PubMed)

Tonelli M, Muntner P, Lloyd A, Manns BJ, Klarenbach S, Pannu N, James MT, Hemmelgarn BR; Alberta Kidney Disease Network. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet. 2012 Sep 1;380(9844):807-14. doi: 10.1016/S0140-6736(12)60572-8. Epub 2012 Jun 19.

Reference Type BACKGROUND
PMID: 22717317 (View on PubMed)

Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999 May;55(5):1899-911. doi: 10.1046/j.1523-1755.1999.00422.x.

Reference Type BACKGROUND
PMID: 10231453 (View on PubMed)

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R; SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92. doi: 10.1016/S0140-6736(11)60739-3. Epub 2011 Jun 12.

Reference Type BACKGROUND
PMID: 21663949 (View on PubMed)

Wanner C, Tonelli M; Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group Members. KDIGO Clinical Practice Guideline for Lipid Management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. 2014 Jun;85(6):1303-9. doi: 10.1038/ki.2014.31. Epub 2014 Feb 19.

Reference Type BACKGROUND
PMID: 24552851 (View on PubMed)

AIM-HIGH Investigators; Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011 Dec 15;365(24):2255-67. doi: 10.1056/NEJMoa1107579. Epub 2011 Nov 15.

Reference Type BACKGROUND
PMID: 22085343 (View on PubMed)

Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):565-71. doi: 10.1016/S0140-6736(12)61190-8.

Reference Type BACKGROUND
PMID: 22883507 (View on PubMed)

Leaf A, Kang JX, Xiao YF, Billman GE. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation. 2003 Jun 3;107(21):2646-52. doi: 10.1161/01.CIR.0000069566.78305.33. No abstract available.

Reference Type BACKGROUND
PMID: 12782616 (View on PubMed)

Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004 Jul;39(1):212-20. doi: 10.1016/j.ypmed.2004.02.030.

Reference Type BACKGROUND
PMID: 15208005 (View on PubMed)

Block RC, Harris WS, Reid KJ, Spertus JA. Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes? Am Heart J. 2008 Dec;156(6):1117-23. doi: 10.1016/j.ahj.2008.07.014. Epub 2008 Oct 14.

Reference Type BACKGROUND
PMID: 19033007 (View on PubMed)

An WS, Kim SE, Kim KH, Lee S, Park Y, Kim HJ, Vaziri ND. Comparison of fatty acid contents of erythrocyte membrane in hemodialysis and peritoneal dialysis patients. J Ren Nutr. 2009 Jul;19(4):267-74. doi: 10.1053/j.jrn.2009.01.027.

Reference Type BACKGROUND
PMID: 19539181 (View on PubMed)

An WS, Lee SM, Son YK, Kim SE, Kim KH, Han JY, Bae HR, Rha SH, Park Y. Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients. Nutr Res. 2012 Jul;32(7):495-502. doi: 10.1016/j.nutres.2012.06.005. Epub 2012 Jul 20.

Reference Type BACKGROUND
PMID: 22901557 (View on PubMed)

Other Identifiers

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prava_2016

Identifier Type: -

Identifier Source: org_study_id

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