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

Sim Ye Ong, Lara Dolling, Jeannette L Dixon, Amanda J Nicoll, Lyle C Gurrin, Michelle Wolthuizen, Erica Michelle Wood, Gregory 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 Delatycki

Research output: Contribution to journalArticleOther

9 Citations (Scopus)

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 ?g/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 ?g/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.
Original languageEnglish
Article numbere008938
Pages (from-to)1 - 7
Number of pages7
JournalBMJ Open
Volume5
Issue number8
DOIs
Publication statusPublished - 2015

Cite this

Ong, S. Y., Dolling, L., Dixon, J. L., Nicoll, A. J., Gurrin, L. C., Wolthuizen, M., Wood, E. M., Anderson, G. J., Ramm, G. A., Allen, K. J., Olynyk, J. K., Crawford, D., Kava, J., Ramm, L. E., Gow, P., Durrant, S., Powell, L. W., & Delatycki, M. (2015). Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron). BMJ Open, 5(8), 1 - 7. [e008938]. https://doi.org/10.1136/bmjopen-2015-008938