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

Sponsor

Dong-A University (Other)

Overall Status

Completed

CT.gov ID

NCT02863185

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

22.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with chronic kidney disease (CKD) are high risk for death and cardiac disease is the major cause of death. CKD patients commonly have traditional risk factors for coronary artery disease, such as age, gender, hypertension, cigarette smoking, and dyslipidemia. Previous studies have reported that reducing cholesterol levels is associated with reducing morbidity and mortality from atherosclerosis. In particular, pharmacologic treatment using statin has been decreased the risk of adverse cardiovascular events in CKD population. Therefore, guidelines recommended the use of statin in CKD patients. On the other hands, niacin or fibrates is not recommended concomitantly with statins in patients with CKD because of increased risk of adverse events. In addition, recent study has reported that there was no incremental clinical benefit from the addition of niacin to statin therapy, in further decreasing the incidence of major cardiac events.

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-thrombic effects. In addition, omega-3 FA modulates cell membrane receptors and affects signal transduction and eicosanoid metabolism. The erythrocyte membrane content of FA has been shown to correlated with the FA content of the myocardium. The risk of cardiovascular disease is significantly reduced in patients with high omega-3 FA, such as eicosapentanoic acid or docosahexaenoic acid (DHA), in the erythrocyte membrane. In contrast, high levels of erythrocyte membrane total trans-FA, trans-oleic acid, and arachidonic acid (AA) are associated with an increased risk of cardiovascular disease. Erythrocyte membrane monounsaturated FA (MUFA) content, including oleic acid, is significantly higher in patients with acute coronary syndrome than control subjects. The erythrocyte membrane oleic acid content was also higher in dialysis patients who have high risks of cardiovascular disease compared to control subjects. Therefore, the modification of erythrocyte membrane FA content is very important with respect to cardiovascular disease. In a previous study, erythrocyte membrane omega-3 FA was shown to be increased and the MUFA content was decreased after omega-3 FA supplementation in HD patients. However, there are no reports about the effect of statin on the erythrocyte membrane FA composition in CKD. Recent study has reported that those with pitavastatin 4mg were decreased DHA to AA ratio, but those with pravastatin 20 mg were not change the DHA to AA ratio in patient with CAD. Statin may have important role on the modulation of erythrocyte membrane FA. In this study, the investigators hypothesized that pitavastatin supplementation can modify erythrocyte membrane FA content, including MUFA and oleic acid, in CKD patients. In addition, the investigators evaluated the effect of pitavastatin on adiponectin and glucose level in CKD patients.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Pitavastatin Drug: Atorvastatin	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 1, 2016

Actual Primary Completion Date :

Dec 31, 2020

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pitavastatin group Use of 2mg or 4mg Pitavastatin	Drug: Pitavastatin
Active Comparator: Atorvastatin group Use of 10mg or 20mg Atorvastatin	Drug: Atorvastatin

Arm

Intervention/Treatment

Experimental: Pitavastatin group

Use of 2mg or 4mg Pitavastatin

Drug: Pitavastatin

Active Comparator: Atorvastatin group

Use of 10mg or 20mg Atorvastatin

Drug: Atorvastatin

Outcome Measures

Primary Outcome Measures

mean difference and change of erythrocyte membrane fatty acid including oleic acid [baseline and 24 weeks after intervention]

Secondary Outcome Measures

mean difference and change of total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol [baseline and 24 weeks after intervention]
mean difference and change of adiponectin [baseline and 24 weeks after intervention]
mean difference and change of glucose and glycosylated hemoglobin [baseline and 24 weeks after intervention]
mean difference and change of proteinuria [baseline and 24 weeks after intervention]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

CKD patients who agreed with written informed consent
CKD patients who do not taking statin agent.
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