Cytochrome P450 2E1 and Iron Overload

Sponsor

Rennes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00138684

Collaborator

Ministry of Health, France (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance Iron Overload	Procedure: venesection	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cytochrome P450 2E1 and Iron Overload

Study Start Date :

Sep 1, 2003

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Feb 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Venesection therapy	Procedure: venesection Venesection therapy is realised every 7 - 14 days until iron desaturation completion.
No Intervention: no venesection therapy

Arm

Intervention/Treatment

Experimental: Venesection therapy

Procedure: venesection

Venesection therapy is realised every 7 - 14 days until iron desaturation completion.

No Intervention: no venesection therapy

Outcome Measures

Primary Outcome Measures

variation of chlorzoxazone metabolization rate measured before and after venesection [Baseline and after iron desaturation completion]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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)