Vitamin E Supplement in Patients With Cirrhosis and Acanthocytosis

Cirrhosis Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01463735
• Other study ID #: CER 10-099
• Status: Completed
• Phase: Phase 2
• First received: October 19, 2011
• Last updated: March 17, 2014
• Start date: November 2011
• Est. completion date: May 2013

Study information

• Verified date: March 2014
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cirrhosis
• Liver Cirrhosis

Intervention

Dietary Supplement:
• Vitamin E supplement (tocofersolan)
700 mg per day per os (i.e. 350 mg twice a day with meals)

Locations

Country	Name	City	State
Switzerland	University Hospitals	Geneva 14

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C/P (cholesterol to phospholipid) ratio of erythrocyte membrane before and after tocofersolan		8 weeks	No
Secondary	percentage of acanthocytes in peripheral blood before and after tocofersolan		8 weeks	No
Secondary	plasma levels of vit E before and after tocofersolan		8 weeks	No