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

NCT ID: NCT00658164

Last Updated: 2008-04-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31

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.

Conditions

Nonalcoholic Fatty Liver Disease

Keywords

Nonalcoholic fatty liver disease associated with increased iron stores

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Iron depletion treatment

Intervention Type: OTHER

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

Interventions

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

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Prof. Silvia Fargion

Locations

U.O. Medicina Interna 1/B

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Silvia Fargion, prof

Role: CONTACT

Phone: 39-02-5503-3301

Email: silvia.fargion@unimi.it

Facility Contacts

Silvia Fargion, Prof.

Role: primary

Other Identifiers

111.2007

Identifier Type: -

Identifier Source: org_study_id