Lipid-lowering Therapies in Vietnamese Chronic Kidney Disease Population

Study Overview
=================
Brief Summary
-----------------
This study aims to determine the mechanisms underlying dyslipidemia in chronic kidney disease (CKD) and effect of lipid-lowering therapies in patients with CKD via parameters of lipid, oxidative stress, tryptophan delegation as well as renal function and side effects. Thirty 3,4 CKD patients with low-density lipoprotein (LDL) > 100 mg/mL (2,59mmol/l), randomly receive three different LDL lipid-lowering therapies: Simvastatin (40 mg/day) or ezetimibe/simvastatin combination (10/20 mg/day or 10/40 mg/day).

Detailed Description
-----------------
The prevalence of chronic kidney disease (CKD) in Vietnamese population is increasing along with hypertension and diabetes. In CKD patient, cardiovascular disease (CVD) is the leading cause of mortality. The lipidemic disorder is one of the CV risk factors in CKD but it was not fully concerned in Viet Nam. Hypocholesterolemia therapy has shown many benefits; however, its effects on OS and endothelial function are still not fully evidenced. In clinical practice, physicians always concern the effects and safety before giving the prescription. However, despite the high frequency of statin treatment, only 1/3 of CKD patients achieved the LDL-C goal. Whether high-dose of statins mono-therapy is more effective in LDL-C lowering is still unclear, but are associated with a high rate of hepatotoxicity, myopathy. Lowering LDL-C with statin mono-therapy and statin/ezetimibe combination reduces the risk of CVD in population without kidney disease. Which Cholesterol-lowering therapies are suitable for stage 3,4 CKD patients in term of e-GFR reduction and side effects? There is no data related to this field in the Vietnamese CKD population. Thus, more advanced lipid-lowering therapies and a better understanding of the mechanism is needed for treatment strategy of hyperlipidemia in Vietnamese patients with CKD.

Official Title
-----------------
Lipid-lowering Regimes Improve Oxidative Stress, Tryptophan Degradation in Hypercholesterolemia Chronic Kidney Disease Patients

Conditions
-----------------
Hypercholesterolemia, Chronic Kidney Diseases

Intervention / Treatment
-----------------
* Drug: Simvastatin 40mg
* Drug: Ezetimibe/simvastatin 10/20 mg/day
* Drug: Ezetimibe/simvastatin 10/40 mg/day


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages Eligible for Study: ≥ 50 years old but not treated with chronic dialysis or kidney transplantation In adults aged 18-49 years with CKD but not treated with chronic dialysis or kidney transplantation, statin treatment in people with one or more of the following: known coronary disease (myocardial infarction or coronary revascularization); diabetes mellitus; prior ischemic stroke; estimated 10-year incidence of coronary death or non-fatal myocardial infarction > 10%. CKD in the 3,4 stage: (e-GFR: 15-60 ml/min/1.73 m2) CKD proteinuria (defined as Creatinine clearance >20 ml/min/1.73 m2 combines with urinary protein excretion rate >300mg/24 h) LDL cholesterol concentration > 100 mg/dl (2,59 mmol/l) Exclusion Criteria: In adults with dialysis-dependent CKD Heart failure (New York Heart Association class III or more) Previous or concomitant treatment with corticoids, statin, immunosuppressive agents, vitamin B6, B12, folate. Pregnancy Patients who do not agree to participate the research Patients are unable to understand the purposes and the risks of the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: simvastatin treatment<br> | Drug: Simvastatin 40mg<br>* Simvastatin mono-therapy at the dose of 40 mg/day for 12 months<br>|
| Sham Comparator: EZE/simvastatin 10/20 mg treatment<br> | Drug: Ezetimibe/simvastatin 10/20 mg/day<br>* Ezetimibe/simvastatin combined therapy at the dose of 10/20 mg/day for 12 months<br>|
| Sham Comparator: EZE/simvastatin 10/40 mg treatment<br> | Drug: Ezetimibe/simvastatin 10/40 mg/day<br>* Ezetimibe/simvastatin combined therapy at the dose of 10/40 mg/day for 12 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin in Vietnamese CKD population and in healthy persons at the base time. | The serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin will be measured in mg/dL. | At the base time | 
| To measure the serum level of Taurine, Tryp, and Kyn in Vietnamese CKD population and in healthy persons at the base time. | The serum level of Taurine, Tryp, and Kyn will be measured in micromol/L | At the base time | 
| To measure the number of red blood cell, white blood cell and platelet in Vietnamese CKD population and in healthy persons at the base time. | The number of red blood cell, white blood cell, and platelet will be measured in number/L | At the base time | 
| To measure the serum level of MDA in Vietnamese CKD population and in healthy persons at the base time. | The serum level of MDA will be measured in nmol/L | At the base time | 
| To measure the level of Albuminuria and urine Creatinine in Vietnamese CKD population and in healthy persons at the base time. | The serum level of Albuminuria and urine Creatinine will be measured in mg/dL | At the base time | 
| To measure the serum level of SGOT, SGPT, and Creatinin Kinase in Vietnamese CKD population and in healthy persons at the base time. | The serum level of SGOT, SGPT and Creatinin Kinase will be measured in Units/L | At the base time | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin in Vietnamese CKD population at 4th, 8th, 12th month. | The serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin will be measured in mg/dL. The change of results during treatment will be described and will be compared in 3 different groups | at 4th, 8th and 12th month | 
| To measure the serum level of Taurine, Tryp, and Kyn in Vietnamese CKD population at 4th, 8th, 12th month. | The level of Taurine, Tryp, and Kyn will be measured in micromol/L. The change of results during treatment will be described and will be compared in 3 different groups | at 4th, 8th and 12th month | 
| To measure the number of red blood cell, white blood cell and platelet in Vietnamese CKD population at 4th, 8th, 12th month. | The number of red blood cell, white blood cell, and platelet will be measured in number/L. The change of results during treatment will be described and will be compared in 3 different groups | at 4th, 8th and 12th month | 
| To measure the serum level of MDA in Vietnamese CKD population at 4th, 8th, 12th month. | The serum level of MDA will be serum in nmol/L. The change of results during treatment will be described and will be compared in 3 different groups | at 4th, 8th and 12th month | 
| To measure the serum levels of SGOT, SGPT and Creatinine Kinase in Vietnamese CKD population at 4th month, 8th month and the 12th month | The unexpected effects of each treatment therapy on the liver and on the muscle will be accessed by measuring the level of SGOT, SGPT and Creatinine Kinase. These laboratory test will be measured at 4th month, 8th month and the 12th month. These results will be compared in 3 different groups | at 4th, 8th and 12th month | 
| To measure the level of Albuminuria and urine Creatinine in Vietnamese CKD population at 4th, 8th, 12th month. | The level of Albuminuria and urine Creatinine will be measured in mg/dL. The change of results during treatment will be described and will be compared in 3 different groups | at 4th, 8th and 12th month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lipid lowering therapy, Chronic kidney disease, Hypercholesterolemia