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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
100
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.
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.
Royal Brisbane and Woman's Hospital
Brisbane, Queensland, Australia
Austin Health
Melbourne, Victoria, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia
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.
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.
Change in markers of liver fibrosis
Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).
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
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.
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
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.
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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
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.
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
To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.
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).