Mi-iron - Moderately Increased Iron - is Reducing Iron Overload Necessary? - Clinical Trial for Hereditary Haemochromatosis | NCT01631708

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

Australia

Study Type

Interventional

Intervention

Erythrocytapheresis

Plasmapheresis

About this trial

This is an interventional treatment trial for Hereditary Haemochromatosis focused on measuring Hereditary haemochromatosis, Moderate iron overload, Serum ferritin, Treatment

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Royal Brisbane and Woman's Hospital
Austin Health
Royal Melbourne Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Erythrocytapheresis

Plasmapheresis

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in markers of liver fibrosis

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

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.

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.

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.

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.

Full Information

NCT ID

NCT01631708

First Posted

June 24, 2012

Last Updated

September 25, 2016

Sponsor

Murdoch Childrens Research Institute

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01631708

Brief Title

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

Acronym

Mi-iron

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

June 2012 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Murdoch Childrens Research Institute

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hereditary Haemochromatosis

Keywords

Hereditary haemochromatosis, Moderate iron overload, Serum ferritin, Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

Participant

Allocation

Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Erythrocytapheresis

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Plasmapheresis

Arm Type

Sham Comparator

Arm Description

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.

Intervention Type

Procedure

Intervention Name(s)

Erythrocytapheresis

Other Intervention Name(s)

red blood cell removal, red blood cell apheresis

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Plasmapheresis

Other Intervention Name(s)

plasma removal, sham erythrocytapheresis

Intervention Description

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.

Primary Outcome Measure Information:

Title

Fatigue

Description

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.

Secondary Outcome Measure Information:

Title

Change in markers of liver fibrosis

Description

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

Time Frame