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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00658164
Recruitment Status : Unknown
Verified July 2007 by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
Recruitment status was:  Recruiting
First Posted : April 14, 2008
Last Update Posted : April 14, 2008
Information provided by:
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

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 baseline hemoglobin values and venesection tolerance, until ferritin < 30 ng/ml and transferrin saturation < 25%. Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. Smaller phlebotomies (250 cc) will be allowed for carriers of beta-thalassaemia trait. Maintenance phlebotomies (as much as required) will then be instituted to keep iron stores depleted (ferritin < 50 ng/ml and transferrin saturation < 25%, MCV <85 fl). Before starting treatment, patients will undergo ECG, and in the presence of hyperglycemia or hypertension also echocardiography (see exclusion criteria).

Change in diabetes medication dosage or start of new therapy will be allowed for HbA1C values <6% or ≥ 7%. According to accepted criteria, previously untreated patients should be treated with metformin. If possible, newly diagnosed hypertension should be treated with Ace-inhibitors.

Condition or disease Intervention/treatment Phase
Nonalcoholic Fatty Liver Disease Other: Iron depletion treatment Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : October 2007
Estimated Primary Completion Date : March 2009

Arm Intervention/treatment
Experimental: 1 Other: Iron depletion treatment
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

Primary Outcome Measures :
  1. To determine in a 24 month controlled study whether iron depletion by phlebotomy improves insulin sensitivity, and thereby reduces hepatic steatosis and inflammation in subjects with nonalcoholic steatohepatitis [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. To assess the effect of iron depletion on glucose tolerance status. Glucose tolerance will be determined by OGTT in subjects without type 2 diabetes (T2D), and by HbA1c levels and the change in dosage of pharmacological therapy in those with T2D. [ Time Frame: 24 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00658164

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Contact: Silvia Fargion, prof 39-02-5503-3301

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U.O. Medicina Interna 1/B Recruiting
Milan, Italy, 20122
Contact: Silvia Fargion, Prof.    39-02-5503-3301   
Principal Investigator: Silvia Fargion, Prof.         
Sub-Investigator: Luca Valenti, Md         
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

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Responsible Party: Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Prof. Silvia Fargion Identifier: NCT00658164     History of Changes
Other Study ID Numbers: 111.2007
First Posted: April 14, 2008    Key Record Dates
Last Update Posted: April 14, 2008
Last Verified: July 2007
Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Nonalcoholic fatty liver disease associated with increased iron stores
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Trace Elements
Growth Substances
Physiological Effects of Drugs