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Completed

NCT Number: NCT01631708

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.

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Key information

Conditions

Hereditary Haemochromatosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hemochromatosis Iron Metabolism Disorders Iron Overload Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Royal Brisbane and Woman's Hospital, Brisbane, Queensland, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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).

Exclusion criteria

  • 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.

Treatment and study plan

Erythrocytapheresis

Procedure

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.

Other names: red blood cell removal, red blood cell apheresis

Plasmapheresis

Procedure

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.

Other names: plasma removal, sham erythrocytapheresis

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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).

    Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).

  2. 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).

    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.

  3. 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).

    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.

  4. 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).

    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.

  5. 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).

    To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.

Sponsors and collaborators

Lead sponsor

Murdoch Childrens Research Institute

Other

Collaborators

  • Austin Health
  • Fremantle Hospital and Health Service
  • Melbourne Health
  • Royal Brisbane and Women's Hospital
  • The University of Queensland

Registry information

Acronym: Mi-iron

Important dates

Study start
2012
Primary completion
2016
Study completion
2016
First posted
Jun 29, 2012
Registry last updated
Sep 27, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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