None listed
Conditions
Brief summary
Fat and inflammation in the liver caused by insulin resistance and oxidative stress is termed nonalcoholic steatohepatitis (NASH). NASH is the commonest cause of hepatitis in Australia and may lead to cirrhosis, liver cancer and death. Current therapies are largely ineffective. Iron in the body has been linked to promoting insulin resistance and oxidative stress and thus represents a suitable treatment target. This proposal examines the effect of removing iron by venesection in patients with NASH compared to controls. The effect on insulin resistance, oxidative stress and liver fat, inflammation and scarring will be assessed during the trial.
Interventions
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 lifest
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
Sponsors
Raines Medical Research Foundation
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Biopsy demonstrating NASH within six months of trial entry.
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)
Outcome results
None listed