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

NCT01631708 | Completed DMC

• 1 other identifier: 04609
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

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.

Conditions

Hereditary Haemochromatosis

Keywords

Hereditary haemochromatosis; Moderate iron overload; Serum ferritin; Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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

  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

  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).

Study Arms (2)

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.

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.

Procedure: Plasmapheresis

Interventions

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.

Also known as: red blood cell removal, red blood cell apheresis

Erythrocytapheresis

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.

Also known as: plasma removal, sham erythrocytapheresis

Plasmapheresis

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Austin Health: collaborator
• Royal Brisbane and Women's Hospital: collaborator
• Fremantle Hospital and Health Service: collaborator
• Melbourne Health: collaborator
• The University of Queensland: collaborator

Study Sites (3)

Royal Brisbane and Woman's Hospital

Brisbane, Queensland, 4072, Australia

Location

Austin Health

Melbourne, Victoria, 3081, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

Related Publications (2)

• 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.

  PMID: 29195602 DERIVED

• 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.

  PMID: 26270952 DERIVED

Related Links

• Haemochromatosis Australia homepage

MeSH Terms

Conditions

Hemochromatosis

Interventions

Plasmapheresis

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Martin B Delatycki

  Austin Health/Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 24, 2012
• First Posted: June 29, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: September 27, 2016

Record last verified: 2016-09

Locations

AU (3)