TY - JOUR
T1 - Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron)
AU - Ong, Sim Ye
AU - Dolling, Lara
AU - Dixon, Jeannette L
AU - Nicoll, Amanda J
AU - Gurrin, Lyle C
AU - Wolthuizen, Michelle
AU - Wood, Erica Michelle
AU - Anderson, Gregory J
AU - Ramm, Grant A
AU - Allen, Katrina J
AU - Olynyk, John K
AU - Crawford, Darrell
AU - Kava, Jennifer
AU - Ramm, Louise E
AU - Gow, Paul
AU - Durrant, Simon
AU - Powell, Lawrie W
AU - Delatycki, Martin
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/record/display.uri?eid=2-s2.0-84941630918&origin=inward&txGid=0#
UR - https://www.scopus.com/pages/publications/84941630918
U2 - 10.1136/bmjopen-2015-008938
DO - 10.1136/bmjopen-2015-008938
M3 - Article
SN - 2044-6055
VL - 5
SP - 1
EP - 7
JO - BMJ Open
JF - BMJ Open
IS - 8
M1 - e008938
ER -
