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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Murdoch Childrens Research Institute
Sponsor:
Collaborators:
Austin Health
Royal Brisbane and Women's Hospital
Fremantle Hospital and Health Service
Melbourne Health
The University of Queensland
Information provided by (Responsible Party):
Martin Delatycki, Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier:
NCT01631708
First received: June 24, 2012
Last updated: March 30, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Hereditary Haemochromatosis
Procedure: Erythrocytapheresis
Procedure: Plasmapheresis

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?

Resource links provided by NLM:


Further study details as provided by Murdoch Childrens Research Institute:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • 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). ] [ Designated as safety issue: Yes ]
    Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).

  • 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). ] [ Designated as safety issue: No ]
    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.

  • 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). ] [ Designated as safety issue: No ]
    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.

  • 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). ] [ Designated as safety issue: No ]
    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.

  • 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). ] [ Designated as safety issue: Yes ]
    To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.


Estimated Enrollment: 110
Study Start Date: June 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Erythrocytapheresis

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

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 Name: red blood cell removal, red blood cell apheresis
Sham Comparator: Plasmapheresis

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
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 Name: plasma removal, sham erythrocytapheresis

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631708

Contacts
Contact: Martin B Delatycki +61 3 9496 4355 martin.delatycki@ghsv.org.au

Locations
Australia, Queensland
Royal Brisbane and Woman's Hospital Recruiting
Brisbane, Queensland, Australia, 4072
Contact: Lawrie Powell, Prof         
Contact: Jeannette Dixon    07 33620172    Jeannette.Dixon@qimrberghofer.edu.au   
Principal Investigator: Lawrie Powell, Prof         
Australia, Victoria
Austin Health Recruiting
Melbourne, Victoria, Australia, 3081
Contact: Martin B Delatycki, Prof    +61 3 9496 4355    martin.delatycki@ghsv.org.au   
Contact: Lara Dolling    03949 64335    lara.dolling@mcri.edu.au   
Principal Investigator: Martin B Delatycki, Prof         
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Amanda Nicoll, A/Prof         
Contact: Lara Dolling    03 9496 4335    lara.dolling@mcri.edu.au   
Principal Investigator: Amanda Nicoll, A / Prof         
Australia, Western Australia
Fremantle Hospital and Health Service Recruiting
Perth, Western Australia, Australia, 6009
Contact: John Olynyk         
Principal Investigator: John Olynyk, Prof         
Sponsors and Collaborators
Murdoch Childrens Research Institute
Austin Health
Royal Brisbane and Women's Hospital
Fremantle Hospital and Health Service
Melbourne Health
The University of Queensland
Investigators
Principal Investigator: Martin B Delatycki Austin Health/Murdoch Childrens Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Martin Delatycki, Professor, Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier: NCT01631708     History of Changes
Other Study ID Numbers: 04609
Study First Received: June 24, 2012
Last Updated: March 30, 2014
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by Murdoch Childrens Research Institute:
Hereditary haemochromatosis
Moderate iron overload
Serum ferritin
Treatment

Additional relevant MeSH terms:
Hemochromatosis
Iron Overload
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on October 21, 2014