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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 recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2007 by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier:
NCT00658164
First received: April 9, 2008
Last updated: April 11, 2008
Last verified: July 2007
  Purpose

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 Intervention Phase
Nonalcoholic Fatty Liver Disease
Other: Iron depletion treatment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: October 2007
Estimated Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00658164

Contacts
Contact: Silvia Fargion, prof 39-02-5503-3301 silvia.fargion@unimi.it

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

No publications provided

Responsible Party: Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Prof. Silvia Fargion
ClinicalTrials.gov Identifier: NCT00658164     History of Changes
Other Study ID Numbers: 111.2007
Study First Received: April 9, 2008
Last Updated: April 11, 2008
Health Authority: Italy: Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena

Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Nonalcoholic fatty liver disease associated with increased iron stores

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Iron
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Trace Elements

ClinicalTrials.gov processed this record on November 24, 2014