Vitamin E Supplement in Patients With Cirrhosis and Acanthocytosis

Study Overview
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Brief Summary
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Acanthocytes, also termed spur cell, are large erythrocytes covered with spike-like projections which are associated with severe hemolytic anemia. In advanced cirrhosis, acanthocytes may account for 20 to 30% of red blood cells. Up to 70% of cirrhotic patients display anemia and hemoglobin level may fall to below 5 gr/L in spur cell anemia. The true incidence of spur cells in cirrhosis is not known precisely but may avoisinate 45%, typically in patients with advanced cirrhosis.The presence of spur cells usually predicts lower survival rates. Vitamin E is an antioxidant compound that is a component of biological membrane that helps to maintain integrity of lipid bilayers. Vitamin E deficiency leads to erythrocyte hemolysis, which is improved by supplemental vitamin E. This study is an open label single arm phase II study in cirrhotic patients treated for 4 weeks with Tocofersolan (Vedrop), a water-soluble derivative of alpha-tocopherol, and thus an orally bio-available source of vitamin E. The aim of this study is to determine the effect of tocofersolan on red blood cell membranes lipid composition in adult patients with cirrhosis and vitamin E deficiency. Secondary endpoints are the effects of tocofersolan on anemia, hemolysis and acanthocytosis; on lipid peroxidation and oxidative stress; the safety of a 4 week treatment of 700 mg/day.

Detailed Description
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Background: Cirrhosis may be complicated by the presence of ascites, portosystemic collaterals that may eventually bleed or give rise to hepatic encephalopathy. Laboratory findings in patients with cirrhosis includes alterations in synthetic function as well as an increase in serum bilirubin. Liver diseases are also associated with hematologic complications and altered red blood cells morphology. Up to 70% of cirrhotic patients display anemia and hemoglobin level may fall to below 5 gr/L in spur cell anemia. Thrombocytopenia, leucopenia and neutropenia are also common. In patients with cirrhosis, acanthocytes and echinocytes are reported. Acanthocytes, also termed spur cell, are large erythrocytes covered with spike-like projections which are associated with severe hemolytic anemia. In advanced cirrhosis, acanthocytes may account for 20 to 30% of red blood cells. The spiky morphology of acanthocytes results from an abnormal surface area to volume ratio and an altered membrane lipids composition. These changes in red blood cell membranes render the cell more prone to destruction and hemolysis. The true incidence of spur cells in cirrhosis is not known precisely but may avoisinate 45%, typically in patients with advanced cirrhosis.The presence of spur cells usually predicts lower survival rates. The liver is a very susceptible organ to oxidative-related cellular damage, and low antioxidants, such as vitamin E, in cirrhosis participate in cellular membrane alterations. Vitamin E is an antioxidant compound that is a component of biological membrane that helps to maintain integrity of lipid bilayers. Vitamin E deficiency leads to erythrocyte hemolysis, which is improved by supplemental vitamin E. Tocofersolan (Vedrop) is a water-soluble derivative of alpha-tocopherol, and thus an orally bio-available source of vitamin E. Vitamin E supplementation appears safe in liver diseases and provides histological benefit in NASH. Aim and endpoints I. To determine the effect of tocofersolan on red blood cell membranes lipid composition in adult patients with cirrhosis and vitamine E deficiency II. To determine the effect of vit E on anemia, hemolysis and acanthocytosis; on lipid peroxidation and oxidative stress; the safety of a 4 week treatment of 700 mg/day Duration: selection period: 1 week; active treatment: 4 weeks; follow-up period. 3 weeks. Evaluation time-points: baseline and after 4 weeks of treatment Methodology/Design: phase II pilot trial on 27 patients, single arm study

Conditions
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Cirrhosis

Intervention / Treatment
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* Dietary Supplement: Vitamin E supplement (tocofersolan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Cirrhosis (histology or, if not available, based on clinical, biological and radiological findings) Total bilirubin > 60 µmol/ L Anemia defined as hemoglobin < 120 g/L Vitamin E deficiency as defined by plasma levels < 23 µmol/L Exclusion Criteria: Inability or unwillingness to give written consent Parenteral nutrition Co-medication with Orlistat, Colestipol, anticoagulants Active alcohol consumption as assessed by urine analysis Gastro-intestinal bleeding within the past 2 weeks Gastric bypass Moderate to severe renal failure as defined by creatinine clearance < 60 ml/min Hypothyroidism as defined by TSH > 6 mU/L Diagnosis of cancer upon inclusion in the study Any other severe condition affecting interfering with the normal conduct of the study Already participating in another clinical study

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: Vitamin E supplement (tocofersolan)|700 mg per day per os (i.e. 350 mg twice a day with meals)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C/P (cholesterol to phospholipid) ratio of erythrocyte membrane before and after tocofersolan |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of acanthocytes in peripheral blood before and after tocofersolan |  | 8 weeks | 
| plasma levels of vit E before and after tocofersolan |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhotic patients