Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron).

Abstract

INTRODUCTION:

HFE p.C282Y homozygosity is the most common cause of hereditary haemochromatosis. There is currently insufficient evidence to assess whether non-specific symptoms or hepatic injury in homozygotes with moderately elevated iron defined as a serum ferritin (SF) of 300-1000 µg/L are related to iron overload. As such the evidence for intervention in this group is lacking. We present here methods for a study that aims to evaluate whether non-specific symptoms and hepatic fibrosis markers improve with short-term normalisation of SF in p.C282Y homozygotes with moderate elevation of SF.

METHODS AND ANALYSIS:

Mi-iron is a prospective, multicentre, randomised patient-blinded trial conducted in three centres in Victoria and Queensland, Australia. Participants who are HFE p.C282Y homozygotes with SF levels between 300 and 1000 μg/L are recruited and randomised to either the treatment group or to the sham treatment group. Those in the treatment group have normalisation of SF by 3-weekly erythrocytapheresis while those in the sham treatment group have 3-weekly plasmapheresis and thus do not have normalisation of SF. Patients are blinded to all procedures. All outcome measures are administered prior to and following the course of treatment/sham treatment. Patient reported outcome measures are the Modified Fatigue Impact Scale (MFIS-primary outcome), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-item short form V.2 (SF36v2) and Arthritis Impact Measurement Scale 2 short form (AIMS2-SF). Liver injury and hepatic fibrosis are assessed with transient elastography (TE), Fibrometer and Hepascore, while oxidative stress is assessed by measurement of urine and serum F2-isoprostanes.

ETHICS AND DISSEMINATION:

This study has been approved by the Human Research Ethics Committees of Austin Health, Royal Melbourne Hospital and Royal Brisbane and Women's Hospital. Study findings will be disseminated through peer-reviewed publications and conference presentations.

TRIAL REGISTRATION:

Trial identifier: NCT01631708; Registry: ClinicalTrials.gov.

• Authors: Sim Yee Ong, Lara Dolling, Jeannette L Dixon, Amanda J Nicoll, Lyle C Gurrin, Michelle Wolthuizen, Erica M Wood, Greg J Anderson, Grant A Ramm, Katrina J Allen, John K Olynyk, Darrell Crawford, Jennifer Kava, Louise E Ramm, Paul Gow, Simon Durrant, Lawrie W Powell, Martin B Delatycki
• Journal: BMJ open (BMJ Open) Vol. 5 Issue 8 Pg. e008938 (Aug 12 2015) ISSN: 2044-6055 [Electronic] England
• PMID: 26270952 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• HFE protein, human
• Hemochromatosis Protein
• Histocompatibility Antigens Class I
• Membrane Proteins
• Ferritins

Topics

• Adolescent
• Adult
• Aged
• Blood Component Removal
• Erythrocyte Transfusion
• Ferritins (blood)
• Hemochromatosis Protein
• Histocompatibility Antigens Class I (genetics)
• Homozygote
• Humans
• Iron Overload (therapy)
• Membrane Proteins (genetics)
• Middle Aged
• Prospective Studies
• Treatment Outcome
• Young Adult