Cytochrome P450 2E1 and Iron Overload

Insulin Resistance Clinical Trial

Official title:

Cytochrome P450 2E1 and Iron Overload

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00138684
• Other study ID #: DGS 2003/0052
• Secondary ID: PHRC/02-09CIC020
• Status: Completed
• Phase: Phase 2
• First received: August 29, 2005
• Last updated: May 18, 2012
• Start date: September 2003
• Est. completion date: February 2006

Study information

• Verified date: May 2012
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 2006
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance
• Iron Overload

Intervention

Procedure:
• venesection
Venesection therapy is realised every 7 - 14 days until iron desaturation completion.

Locations

Country	Name	City	State
France	CHU Nantes	Nantes
France	Unité d'Investigation Clinique - Hôpital Pontchaillou	Rennes

Sponsors (2)

Lead Sponsor	Collaborator
Rennes University Hospital	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	variation of chlorzoxazone metabolization rate measured before and after venesection		Baseline and after iron desaturation completion	No
Secondary	variation of blood Malonedialdehyde rate		Baseline and after iron desaturation completion	No
Secondary	variation of blood 4-hydroxynonenal rate		Baseline and after iron desaturation completion	No
Secondary	variation of blood Glutathion rate		Baseline and after iron desaturation completion	No
Secondary	variation of serum Vitamin E rate		Baseline and after iron desaturation completion	No
Secondary	Variation of serum Vitamin C rate		Baseline and after iron desaturation completion	No