Effects of Carnitine on Oxidative Stress to IVIR Administration to CKD Patients:Impact of Haptoglobin Genotype

Study Overview
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Brief Summary
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Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2-2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin genotype affects iron-induced oxidative stress in CKD patients. In this proposed study we wished to examine whether Hp genotype influences intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and its impact on the response of these patients to L-Carnitine therapy.

Detailed Description
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This study will include at least 25 anemic CKD patients (stages 3-4) that will be given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20mg/kg, IV) prior to IVIR. Weekly blood samples will drawn before and after each IVIR for Hp genotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses.

Official Title
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Effects of Carnitine on Oxidative Stress and Inflammatory Responses to Intravenous Iron Administration to Patients With CKD: Impact of Haptoglobin Genotype

Conditions
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Anemia

Intervention / Treatment
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* Drug: L-Canitine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients that have been diagnosed as suffering from chronic kidney diseases at stages 3-4 and confirmed by MDRD. CKD patients with Hb of less than 10 g%. At age ≥18 y. Exclusion Criteria: Pregnant women. Patient with CKD stage 5 on Dialysis. Patients with severe liver diseases. Patients with severe CHF. Inter-current illness such as fever. Allergic rhinitis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: IVIR<br>Patients given IV iron (Sodium ferric gluconate, [125 mg/100 ml] from week 1 to week 4 | |
| Experimental: IVIR Carnitine<br>Patients given Carnitine (20mg/kg, IV) perior to IV iron (Sodium ferric gluconate, [125 mg/100 ml] from week 4 to week 8. | Drug: L-Canitine<br>* Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine, it is essential for the transport of fatty acids from the intermembraneous space in the mitochondria, into the mitochondrial matrix during the breakdown of lipids (fats) for the generation of metabolic energy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AOPP (Advanced Oxidation Protein Products) |  | 1 month | 
| neutrophil gelatinase-associated lipocalin (NGAL), |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haptoglobin |  | 1 month |