Status:

UNKNOWN

Effect of Iron Depletion by Phlebotomy Plus Lifestyle Changes vs. Lifestyle Changes Alone on Liver Damage in Patients With Nonalcoholic Fatty Liver Disease With Increased Iron Stores

Lead Sponsor:

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Conditions:

Nonalcoholic Fatty Liver Disease

Eligibility:

All Genders

18-65 years

Phase:

PHASE3

Brief Summary

Patients will be randomized to lifestyle changes alone or lifestyle changes associated with iron depletion. Iron depletion will be achieved by removing 350 cc of blood every 10-15 days according to b...

Eligibility Criteria

Inclusion

  • Age ≥ 18 \< 75 years
  • Ferritin \> 250 ng/ml and/or stainable iron at biopsy
  • NAS ≥ 2 and/or NAS 1 and stage≥1 at liver histology
  • Willingness to maintain diet and exercise during the full course of the study
  • Written informed consent to participate to the study and to have the specific genetic tests performed
  • Ability to comply with all study requirements

Exclusion

  • Pregnant or lactating female
  • Diagnosis of or a history of:
  • Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing's syndrome or acromegaly
  • Acute metabolic complication such as ketoacidosis or hyperosmolar state within the past 6 months
  • Alcohol consumption \> 20 g/day for females and \> 30 g/day for males
  • BMI ≥ 35 Kg/ m2
  • Other liver disease such as viral hepatitis, autoimmune hepatitis, Wilson disease, as defined by ceruloplasmin below normal limits and liver histology consistent with Wilson disease. Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than 80 mg/dl or PiZ/PiZ or PiZ/PiS genotype. \*Hemochromatosis, as defined by homozygosity for the C282Y HFE mutation or compound heterozygosity for C282Y/H63D mutations or Hepatic Iron Index ≥ 1.9.
  • Advanced liver disease (Child B/C cirrhosis), portal hypertension, hepatocellular carcinoma.
  • Congestive heart failure (NYHA I-IV) and unstable ischemic heart disease, systolic dysfunction (ejection fraction \< 45%)
  • Any of the following ECG abnormalities: II or III degree Atrial Ventricular \*Block, QT\>500msec, repolarization defect suggestive of ischemia
  • Malignancy within the last 5 years
  • Serum creatinine levels \> 1.5 mg/dl males, \> 1.4 mg/dl females
  • TSH outside of normal range
  • Use of drugs known to induce NAFLD: corticosteroids, methotrexate, zidovudine, amiodarone, GH, estrogens, tamoxifene, tetracycline
  • Lipodystrophy, dysbetalipoproteinemia, inflammatory bowel disease, HIV infection
  • Basal hemoglobin levels \< 11 g/dl

Key Trial Info

Start Date :

October 1 2007

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

Estimated Enrollment :

150 Patients enrolled

Trial Details

Trial ID

NCT00658164

Start Date

October 1 2007

Last Update

April 14 2008

Active Locations (1)

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U.O. Medicina Interna 1/B

Milan, Italy, 20122