Clinical trial NCT01631708: Mi-iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?
Official title: Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Haemochromatosis
Keywords: Hereditary haemochromatosis
Moderate iron overload
Serum ferritin
Treatment
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
Collaborators: name: Austin Health
name: Royal Brisbane and Women's Hospital
name: Fremantle Hospital and Health Service
name: Melbourne Health
name: The University of Queensland
First posted: 2012-06-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Haemochromatosis is a preventable genetic iron overload disorder. Untreated, it can shorten life due mainly to liver cirrhosis and cancer. It can be prevented by blood donation to maintain normal iron levels. It is unclear, however, whether treatment is necessary when individuals have moderate elevation of iron in the body. This research project will study the effects of treatment in this group by assessing a number of scans, questionnaires and blood tests in treated and untreated individuals.

Detailed description: There is mounting evidence that treatment of moderate iron overload in HFE related hereditary haemochromatosis (HH) is not necessary. This project aims to undertake a randomised patient-blinded trial of erythrocytapheresis compared to sham erythrocytapheresis (using plasmapheresis) in individuals who have serum ferritin (SF) above the upper limit of the normal range but \< 1000ug/L (defined here as moderate iron overload) due to HFE mutations and to compare the prevalence of symptoms and objective markers of disease in the two treatment arms.

Eligibility criteria: Inclusion Criteria:

1. HFE C282Y homozygous.
2. Aged 18 - 70 years .
3. SF above the upper limit of the normal range of 300µg/L but less than 1000µg/L with a currently or previously raised TS (\>greater than the upper limit of normal for the testing laboratory).

Exclusion Criteria:

1. HH due to genotypes other than HFE C282Y homozygosity.
2. Normal SF, SF \> 1000µg/L.
3. Other major risk factor(s) for liver toxicity or other significant co-morbidities including positivity for hepatitis B or C, excess alcohol consumption (\> 60g/day in males and 40g/day in females) or body mass index \> 35.
4. Has had venesection therapy for HH in the last two years.

Primary outcomes:
measure: Fatigue
timeFrame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have approximately 6 third weekly treatments however this will vary depending on initial SF.
Secondary outcomes:
measure: Change in markers of liver fibrosis
timeFrame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).
measure: Quality of life
timeFrame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).
measure: Depression and Anxiety
timeFrame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).
measure: Arthritis
timeFrame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).
measure: Markers of oxidative stress
timeFrame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Royal Brisbane and Woman's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Austin Health/Murdoch Childrens Research Institute
name: Martin B Delatycki
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ong SY, Gurrin LC, Dolling L, Dixon J, Nicoll AJ, Wolthuizen M, Wood EM, Anderson GJ, Ramm GA, Allen KJ, Olynyk JK, Crawford D, Ramm LE, Gow P, Durrant S, Powell LW, Delatycki MB. Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial. Lancet Haematol. 2017 Dec;4(12):e607-e614. doi: 10.1016/S2352-3026(17)30214-4.
citation: Ong SY, Dolling L, Dixon JL, Nicoll AJ, Gurrin LC, Wolthuizen M, Wood EM, Anderson GJ, Ramm GA, Allen KJ, Olynyk JK, Crawford D, Kava J, Ramm LE, Gow P, Durrant S, Powell LW, Delatycki MB. 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. 2015 Aug 12;5(8):e008938. doi: 10.1136/bmjopen-2015-008938.