Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000448347
Ethics application status
Approved
Date submitted
29/07/2008
Date registered
12/09/2008
Date last updated
5/05/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of iron on insulin resistance in people with hepatitis associated with
non-alcoholic fatty liver disease.
Scientific title
Impact of Iron on Insulin Resistance and liver histology in non-alcoholic steatohepatitis.
Secondary ID [1] 654 0
Nil
Universal Trial Number (UTN)
Trial acronym
IIRON study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic fatty liver disease (NAFLD) 3473 0
non-alcoholic steatohepatitis (NASH) 3474 0
Iron overload 3475 0
Insulin resistance 3476 0
Condition category
Condition code
Metabolic and Endocrine 3635 3635 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Therapeutic venesection in non-alcoholic steatohepatitis study participants who have iron overload.

'Visit 1 (Screening) - Obtain informed consent - Inclusion and exclusion criteria - Record medical history including alcohol, dietary and lifestyle - Return within 2 weeks

Visit 2( Baseline-month 0) - Inclusion/exclusion criteria - Physical examination including vital signs, waist and hips measurement - Alcohol and lifestyle questionnaires - Fasting blood test, urine sample - Dietary and lifestyle counselling - Ferriscan - Randomisation

Visit 3 (month 3- for both groups) - Physical examination including vital signs, waist and hips measurement - Alcohol and lifestyle questionnaires - Fasting blood test, urine sample - Dietary and lifestyle counseling Visit 4 (month 18- for both groups) - Physical examination including vital signs, waist and hips measurement - Alcohol and lifestyle questionnaires - Fasting blood test, urine sample - Dietary and lifestyle counseling - Liver biopsy - Ferriscan Liver biopsy and Ferriscan will be performed in two major tertiary teaching hospitals. For the venesection (intervention) group: - Visits will be initially scheduled for 1 month after randomisation, then 3 monthly if necessary - Fortnightly venesection until serum ferritin level is <50 ug/L - Skip one session of venesection if anaemia (Hb <115g/L (female) <135g/L (male) - Further maintenance on a three monthly basis or as frequently as required to keep ferritin level <50ug/L - Iron studies will be performed prior to each venesection - Vital signs and any adverse events will be recorded at each visit.

Duration of each visit:
Visits 1, 2, 3 and 4 (final visit)- between 1- 1.5 hours.

Ferriscan visits- 1 hour

Venesection visits- This can varies between one hour or more depending if there are any adverse events post venesection.

Standard dietary and lifestyle counselling- advice will be given at each visit by the research nurse who is experienced in counselling type 2 diabetics and NAFLD patients, on a generally low fat and low glycaemic index diet, and regular exercise of moderate to high intensity of minimal 60-90 minutes a day. The session will be of approximately 30 minutes duration.

Period of overall intervention is 18 months
Intervention code [1] 3204 0
Treatment: Other
Comparator / control treatment
Controls will be non-venesection but receive the same standard dietary and lifestyle counselling as the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 4532 0
Histological inprovement in NASH as determined by a two point inprovement in the NAS score (NAFLD Activity Score)
Timepoint [1] 4532 0
End of treatment (month 18)
Secondary outcome [1] 7726 0
Steatosis grade as measured by Brunt histological scoring scheme.
Timepoint [1] 7726 0
End of treatment (month 18)
Secondary outcome [2] 7727 0
Necroinflammatory grade as measured by Brunt histological scoring scheme
Timepoint [2] 7727 0
End of treatment (month 18)
Secondary outcome [3] 7728 0
Fibrosis stage as measured by Brunt histological scoring scheme
Timepoint [3] 7728 0
End of treatment (month 18)

Eligibility
Key inclusion criteria
Biopsy demonstrating NASH within six months of trial entry.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to provide informed consent
Ischemic heart disease
Anaemia
Pregnancy or lactation
Ferritin <50 ug/L
Venesection in the previous 12 months prior to trial entry
Other causes of liver disease: positive hepatitis B serology, positive hepatitis C serology, auto-antibodies, alpha-one anti-trypsin level and ceruloplasmin.
Acute or chronic inflammatory con ditions
Hereditary hemochromatosis (C282Y/C282Y or C282Y/H63D HFE gene mutation)
Alcohol consumption >20 grams/dat for males, >10 grams/day for females
Secondary causes of NAFLD (corticosteroids, gastro-intestinal bypass)
Use of anti-oxidants (vitamin E or C) or anti-TNF agents (pentoxifylline)
Poor glycaemic control diabetic (HbA1c>8.0%)
Decompensated cirrhosis INR(international normalized ratio)>1.3, albumin <35mg/dl or bilirubin >20 mmol/l or ascites or hepatic encephalopathy
Bleeding tendency precluding a repeat liver biopsy
Malignancy( excluding basal cell or squamous cell skin cancers)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2008
Actual
20/10/2008
Date of last participant enrolment
Anticipated
31/12/2011
Actual
15/10/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1046 0
6009
Recruitment postcode(s) [2] 1047 0
6008
Recruitment postcode(s) [3] 1048 0
6168
Recruitment postcode(s) [4] 1049 0
6010

Funding & Sponsors
Funding source category [1] 3657 0
Government body
Name [1] 3657 0
Raines Medical Research Foundation/WA Department of Health
Country [1] 3657 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Raines Medical Research Foundation
Address
Hollywood Specialist Centre
95 Monash Avenue
Nedlands
Western Australia 6009
Country
Australia
Secondary sponsor category [1] 3284 0
Government body
Name [1] 3284 0
Western Australia Department of Health
Address [1] 3284 0
189 Royal Street
East Perth
Western Australia 6004
Country [1] 3284 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5711 0
Human Research Ethics Committee, Sir Charles Gairdner Hospital
Ethics committee address [1] 5711 0
Ethics committee country [1] 5711 0
Australia
Date submitted for ethics approval [1] 5711 0
Approval date [1] 5711 0
29/05/2008
Ethics approval number [1] 5711 0
Trial 2008-008

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28788 0
A/Prof Leon Adams
Address 28788 0
Liver Transplant Unit G Block, 6th Floor Sir Charles Gairdner Hospital Nedlands Western Australia 6009
Country 28788 0
Australia
Phone 28788 0
+61 8 93463228
Fax 28788 0
Email 28788 0
[email protected]
Contact person for public queries
Name 11945 0
Leon Adams
Address 11945 0
Liver Transplant Unit
G Block, 6th Floor
Sir Charles Gairdner Hospital
Nedlands
Western Australia 6009
Country 11945 0
Australia
Phone 11945 0
+61 8 93463228
Fax 11945 0
+61 8 93463098
Email 11945 0
[email protected]
Contact person for scientific queries
Name 2873 0
Leon Adams
Address 2873 0
Liver Transplant Unit
G Block, 6th Floor
Sir Charles Gairdner Hospital
Nedlands
Western Australia 6009
Country 2873 0
Australia
Phone 2873 0
+61 8 93463228
Fax 2873 0
+61 8 93463098
Email 2873 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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