Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron)
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 relate...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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BMJ Publishing Group
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/28122 |
| _version_ | 1848752450729672704 |
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| author | Ong, S. Dolling, L. Dixon, J. Nicoll, A. Gurrin, L. Wolthuizen, M. Wood, E. Anderson, G. Ramm, G. Allen, K. Olynyk, John Crawford, D. Kava, J. Ramm, L. Gow, P. Durrant, S. Powell, L. Delatycki, M. |
| author_facet | Ong, S. Dolling, L. Dixon, J. Nicoll, A. Gurrin, L. Wolthuizen, M. Wood, E. Anderson, G. Ramm, G. Allen, K. Olynyk, John Crawford, D. Kava, J. Ramm, L. Gow, P. Durrant, S. Powell, L. Delatycki, M. |
| author_sort | Ong, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T08:08:49Z |
| format | Journal Article |
| id | curtin-20.500.11937-28122 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:08:49Z |
| publishDate | 2015 |
| publisher | BMJ Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-281222017-09-13T15:14:32Z Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) Ong, S. Dolling, L. Dixon, J. Nicoll, A. Gurrin, L. Wolthuizen, M. Wood, E. Anderson, G. Ramm, G. Allen, K. Olynyk, John Crawford, D. Kava, J. Ramm, L. Gow, P. Durrant, S. Powell, L. Delatycki, M. 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/28122 10.1136/bmjopen-2015-008938 BMJ Publishing Group fulltext |
| spellingShingle | Ong, S. Dolling, L. Dixon, J. Nicoll, A. Gurrin, L. Wolthuizen, M. Wood, E. Anderson, G. Ramm, G. Allen, K. Olynyk, John Crawford, D. Kava, J. Ramm, L. Gow, P. Durrant, S. Powell, L. Delatycki, M. Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) |
| title | Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) |
| title_full | Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) |
| title_fullStr | Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) |
| title_full_unstemmed | Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) |
| title_short | Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron) |
| title_sort | should hfe p.c282y homozygotes with moderately elevated serum ferritin be treated? a randomised controlled trial comparing iron reduction with sham treatment (mi-iron) |
| url | http://hdl.handle.net/20.500.11937/28122 |