Cytochrome P450 2E1 and Iron Overload

Study Overview
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Brief Summary
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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.

Official Title
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Cytochrome P450 2E1 and Iron Overload

Conditions
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Insulin Resistance, Iron Overload

Intervention / Treatment
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* Procedure: venesection


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venesection therapy<br> | Procedure: venesection<br>* Venesection therapy is realised every 7 - 14 days until iron desaturation completion.<br>|
| No Intervention: no venesection therapy<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| variation of chlorzoxazone metabolization rate measured before and after venesection |  | Baseline and after iron desaturation completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin resistance, iron overload, phlebotomy, hepatic iron overload