Hereditary HaemochromatosisMi-ironNCT01631708

Mi-iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?

A study testing Erythrocytapheresis and Plasmapheresis in people with Hereditary Haemochromatosis, run by Murdoch Childrens Research Institute at 3 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Hereditary Haemochromatosis
What is being tested?: Erythrocytapheresis and Plasmapheresis
Type of treatment: Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: 3 sitesAustralia
Study dates: Jun 2012to Jul 2016
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

HFE C282Y homozygous.
Aged 18 - 70 years .
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).

Who cannot join

HH due to genotypes other than HFE C282Y homozygosity.
Normal SF, SF > 1000µg/L.
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.
Has had venesection therapy for HH in the last two years.

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

Royal Brisbane and Woman's Hospital
Brisbane, Queensland, 4072
Austin Health
Melbourne, Victoria, 3081
Royal Melbourne Hospital
Melbourne, Victoria

Other trials in Australia

About this study

Official title: Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?

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.

Read the 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.

Conditions: Hereditary Haemochromatosis
Being tested: Erythrocytapheresis, Plasmapheresis
Keywords: Hereditary haemochromatosis, Moderate iron overload, Serum ferritin, Treatment
Medical subject headings: Hemochromatosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ErythrocytapheresisProcedure or surgery
Also called red blood cell removal, red blood cell apheresis
To achieve a blinded randomised trial, apheresis treatment will be used. Those in arm 1 will have erythrocytapheresis reducing iron levels and those in arm 2 will have plasmapheresis and their iron levels will not be reduced.
An apheresis machine will be used to remove red blood cells only from the erythrocytapheresis group. Subjects will have third weekly treatments until SF levels are reduced to ~100 ug/L in accordance with current guidelines.
PlasmapheresisProcedure or surgery
Also called plasma removal, sham erythrocytapheresis
An apheresis machine will be used to remove blood plasma only from the plasmapheresis group. Those in arm 2 will have the approximate number of episodes of apheresis that would be required to reduce their SF to normal had they been randomised to the true treatment arm. Those in the sham arm will be offered to have venesection at their choice of venue or to have their SF normalised by erythrocytapheresis after the initial blinded part of the study. This will be done because it will not be known for some time if there is benefit from normalisation of SF and therefore leaving people with elevated SF that may be harmful.

Study groups in NCT01631708
Study group	Role	What they receive
Erythrocytapheresis	Active comparator	Erythrocytapheresis is a procedure whereby whole blood is drawn from an individual and all elements except erythrocytes are returned to the donor. An automated filtration process removes the erythrocytes. Those in arm 1 will have third weekly erythrocytapheresis until their SF is returned to the normal range. Receives: Procedure: Erythrocytapheresis
Plasmapheresis	Sham comparator	In plasmapheresis, the plasma is removed by the automated filtration process whilst other blood elements including erythrocytes are returned to the subject. Those in arm 2 will have plasmapheresis with the approximate number of episodes of apheresis that would be required to reduce their SF to normal had they been randomised to the true treatment arm. Receives: Procedure: Plasmapheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

Fatigue
Modified Fatigue Impact Scale (MFIS). The MFIS is a shortened version of the Fatigue Impact Scale. This 21-item scale can be self completed and measures the impact of fatigue on physical, cognitive and psychosocial functioning. Each item is scored from 0 (never) to 4 (almost always) resulting in a score from 0-84. In addition, physical (0-36), cognitive (0-40) and psychosocial (0-8) subscale scores can be derived.
Measured: 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 (5)

Change in markers of liver fibrosis
Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).
Measured: 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).
Quality of life
Medical Outcomes Study 36-item short form (SF36). As there are no specific quality of life tools available for HH, we will use this very widely used generic tool that has been used in a number of HH studies. This tool covers eight dimensions of health and wellbeing. One study found that individuals seen in a HH clinic and who had no clinical symptoms had significantly lower scores on a number of dimensions of the SF36 compared to population norms.
Measured: 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).
Depression and Anxiety
The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure designed to screen for anxiety symptoms and depression symptoms in a hospital setting. It is composed of two seven-item subscales, the Anxiety (HADS-A) and Depression (HADS-D) subscales, and a 14-item total scale (HADS-T). Participants use a four-point Likert-type scale to rate how they have felt in the past week. It has been found to be valid and reliable in various populations.
Measured: 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).
Arthritis
The presence and impact of arthritis will be measured by the Arthritis Impact Measurement Scales 2 short form. This is a 24 item validated scale that assesses the impact of arthritis on the individual over the past four weeks. We will also ascertain the use of arthritis medication at baseline and end of erythrocytapheresis/sham erythrocytapheresis.
Measured: 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).
Markers of oxidative stress
To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Jul 2016

First posted29 Jun 2012 (estimated)
Study startJun 2012
Primary completionJul 2016
Study completionJul 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Hereditary HaemochromatosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Single blind
Who is masked: Participant
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01631708
Sponsor's protocol ID: 04609
Acronym: Mi-iron
Status last verified: Sep 2016
First submitted: 24 Jun 2012
Last updated: 27 Sep 2016
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 29195602
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.
PubMed 26270952

Study at a glance

From the registry record, last updated by the sponsor on 27 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?
ClinicalTrials.gov ID: NCT01631708
Acronym / sponsor ID: Mi-iron / 04609
Conditions: Hereditary Haemochromatosis
Keywords: Hereditary haemochromatosis, Moderate iron overload, Serum ferritin, Treatment
Study type: Interventional
Recruitment status: Completed
Enrolment: 100 participants (actual)
Lead sponsor: Murdoch Childrens Research InstituteUniversity, hospital or other
Collaborators: Austin Health, Royal Brisbane and Women's Hospital, Fremantle Hospital and Health Service, Melbourne Health, The University of Queensland
Study start: Jun 2012
Primary completion: Jul 2016 (actual)
Study completion: Jul 2016 (actual)
First posted: 29 Jun 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
Erythrocytapheresis	Active comparator	Procedure: ErythrocytapheresisErythrocytapheresis is a procedure whereby whole blood is drawn from an individual and all elements except erythrocytes are returned to the donor. An automated filtration process removes the erythrocytes. Those in arm 1 will have third weekly erythrocytapheresis until their SF is returned to the normal range.
Plasmapheresis	Sham comparator	Procedure: PlasmapheresisIn plasmapheresis, the plasma is removed by the automated filtration process whilst other blood elements including erythrocytes are returned to the subject. Those in arm 2 will have plasmapheresis with the approximate number of episodes of apheresis that would be required to reduce their SF to normal had they been randomised to the true treatment arm.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

HFE C282Y homozygous.
Aged 18 - 70 years .
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).

Key exclusion criteria (4 listed)

HH due to genotypes other than HFE C282Y homozygosity.
Normal SF, SF > 1000µg/L.
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.
Has had venesection therapy for HH in the last two years.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ErythrocytapheresisAlso: red blood cell removal, red blood cell apheresisTo achieve a blinded randomised trial, apheresis treatment will be used. Those in arm 1 will have erythrocytapheresis reducing iron levels and those in arm 2 will have plasmapheresis and their iron levels will not be reduced. An apheresis machine will be used to remove red blood cells only from the erythrocytapheresis group. Subjects will have third weekly treatments until SF levels are reduced to ~100 ug/L in accordance with current guidelines.	Procedure or surgery	Erythrocytapheresis
PlasmapheresisAlso: plasma removal, sham erythrocytapheresisAn apheresis machine will be used to remove blood plasma only from the plasmapheresis group. Those in arm 2 will have the approximate number of episodes of apheresis that would be required to reduce their SF to normal had they been randomised to the true treatment arm. Those in the sham arm will be offered to have venesection at their choice of venue or to have their SF normalised by erythrocytapheresis after the initial blinded part of the study. This will be done because it will not be known for some time if there is benefit from normalisation of SF and therefore leaving people with elevated SF that may be harmful.	Procedure or surgery	Plasmapheresis

Primary outcome

Fatigue
Time frame: 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.
Modified Fatigue Impact Scale (MFIS). The MFIS is a shortened version of the Fatigue Impact Scale. This 21-item scale can be self completed and measures the impact of fatigue on physical, cognitive and psychosocial functioning. Each item is scored from 0 (never) to 4 (almost always) resulting in a score from 0-84. In addition, physical (0-36), cognitive (0-40) and psychosocial (0-8) subscale scores can be derived.

5 secondary outcomes

Change in markers of liver fibrosis
Time frame: 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).
Quality of life
Time frame: 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).
Depression and Anxiety
Time frame: 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).
Arthritis
Time frame: 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).
Markers of oxidative stress
Time frame: 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).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2016.
Derived from this study: PubMed 29195602Ong 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.
Derived from this study: PubMed 26270952Ong 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.
Haemochromatosis Australia homepageLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Martin B Delatycki principal investigator

Austin Health/Murdoch Childrens Research Institute

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Erythrocytapheresis and Plasmapheresis in people with Hereditary Haemochromatosis, run by Murdoch Childrens Research Institute at 3 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fatigue (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01631708, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2016; AzTrials last refreshed its copy on 31 Oct 2026.