Insulin Resistance, Iron Overload
Conditions
Keywords
insulin resistance, iron overload, phlebotomy, hepatic iron overload
Brief summary
The aim of the study is to determine, in patients presenting hepatic iron overload (genetic haemochtomatisis or dysmetabolic iron overload syndrome), the effects of venesection therapy on cytochrome P450 2E1 activity by comparing the rates of metabolization of chlorzoxazone before and after venesection.
Interventions
PROCEDUREvenesection
Venesection therapy is realised every 7 - 14 days until iron desaturation completion.
Sponsors
Ministry of Health, France
Rennes University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male patients aged from 18 to 70 years * Hepatic iron overload measured by magnetic resonance imaging \[MRI\] (\> 36 µmol/g and \< 200 µmol/L) * Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: * Overweight: BMI \> 25 kg/m2 * Waist/hip circumference (cm) \> 0.90 * Diabetes mellitus (fasting blood glucose level \>1.25g/L or blood glucose level after 2 hours \> 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) * Total cholesterolemia \> 6.2 mmol/L or HDL-Cholesterol \< 0.9 mmol/L * TG\>= 1.7 mmol * Written informed consent Non-Inclusion Criteria: * Consumption of alcohol \> 50 g/day and of any CYP2E1 inhibitor substances * Smoker \> 5 cigarets/day * History of blood donation or venesection * Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. * Inflammatory syndrome (CRP \> 3ng/ml)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| variation of chlorzoxazone metabolization rate measured before and after venesection | Baseline and after iron desaturation completion |
Secondary
| Measure | Time frame |
|---|---|
| variation of blood Malonedialdehyde rate | Baseline and after iron desaturation completion |
| variation of blood 4-hydroxynonenal rate | Baseline and after iron desaturation completion |
| variation of blood Glutathion rate | Baseline and after iron desaturation completion |
| variation of serum Vitamin E rate | Baseline and after iron desaturation completion |
| Variation of serum Vitamin C rate | Baseline and after iron desaturation completion |
Countries
France
Outcome results
None listed