Clinical trial NCT00138684: Cytochrome P450 2E1 and Iron Overload
Official title: Cytochrome P450 2E1 and Iron Overload
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Insulin Resistance
Iron Overload
Keywords: insulin resistance
iron overload
phlebotomy
hepatic iron overload
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2005-08-30
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: variation of chlorzoxazone metabolization rate measured before and after venesection
timeFrame: Baseline and after iron desaturation completion
Secondary outcomes:
measure: variation of blood Malonedialdehyde rate
timeFrame: Baseline and after iron desaturation completion
measure: variation of blood 4-hydroxynonenal rate
timeFrame: Baseline and after iron desaturation completion
measure: variation of blood Glutathion rate
timeFrame: Baseline and after iron desaturation completion
measure: variation of serum Vitamin E rate
timeFrame: Baseline and after iron desaturation completion
measure: Variation of serum Vitamin C rate
timeFrame: Baseline and after iron desaturation completion
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU Nantes
city: Rennes
country: France
facility: Unité d'Investigation Clinique - Hôpital Pontchaillou
Study officials:
affiliation: CHU Rennes
name: Jean-Michel Reymann, PhD
role: STUDY_CHAIR
affiliation: CHU Rennes
name: Fabrice Lainé, MD
role: PRINCIPAL_INVESTIGATOR
References: