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
Recruitment status was Recruiting
Sponsor:
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
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
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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
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 Trace Elements |
Micronutrients Growth Substances Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 22, 2013