Trial record 3 of 3 for:    "Acanthocytosis"

Vitamin E Supplement in Patients With Cirrhosis and Acanthocytosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Laurent Spahr, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01463735
First received: October 19, 2011
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cirrhosis
Dietary Supplement: Vitamin E supplement (tocofersolan)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • C/P (cholesterol to phospholipid) ratio of erythrocyte membrane before and after tocofersolan [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • percentage of acanthocytes in peripheral blood before and after tocofersolan [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • plasma levels of vit E before and after tocofersolan [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 27
Study Start Date: November 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: Vitamin E supplement (tocofersolan)
    700 mg per day per os (i.e. 350 mg twice a day with meals)
Detailed 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01463735

Locations
Switzerland
University Hospitals
Geneva 14, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
  More Information

No publications provided

Responsible Party: Laurent Spahr, Principal Investigator, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01463735     History of Changes
Other Study ID Numbers: CER 10-099
Study First Received: October 19, 2011
Last Updated: March 17, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
Cirrhotic patients

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Vitamins
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2014