Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis

NCT ID: NCT01810965

Last Updated: 2021-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-03
• Study Completion Date: 2019-04-19

Brief Summary

Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France).

For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective.

Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.

Detailed Description

Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France).

For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective.

Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.

The primary objective is to explore the effect of bloodletting upon plasmatic concentrations of NTBI.

The secondary objectives are to:

• explore the impact of bloodletting upon different parameters of iron metabolism and in particular LPI, hepcidinemia and markers of erythropoiesis ;
• explore basal and nycthemeral characteristics of new parameters of iron metabolism (hepcidin, NTBI, LPI) in hemochromatosis patients.

The demonstration of an adverse effect of bloodletting upon iron metabolism would allow for a therapeutic innovation based upon an association of bloodletting and oral chelation during the induction treatment of type 1 hemochromatosis and, more generally in hepcidino deficient forms of hemochromatosis.

Conditions

Hemochromatosis Type 1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort

Group Type: EXPERIMENTAL

First evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)

Intervention Type: PROCEDURE

Interventions

First evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Men
• Age 18 years or older
• Homozygosity for the C282Y mutation of the HFE gene
• With an indication of treatment by bloodletting (in accordance with the French HAS guidelines)
• Ferritinemia ≥ 500µg/L
• Transferrin saturation ≥ 75%
• Never treated by bloodletting
• Written informed consent

Exclusion Criteria

• Contraindication to bloodletting
• Chronic inflammatory or dysmetabolic or neoplastic disease
• Major cardiovascular disease
• Excessive consumption of alcohol (≥ 3gr/day)
• Treatment by iron chelators, C or E vitamins
• Stay in altitude> 1500m in the month preceding the period Day 1
• Patients under guardianship
• Blood donation in the 3 past months
• Night / shift workers

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martine Ropert-Bouchet, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Bruno Laviolle, MD, PhD

Role: STUDY_CHAIR

Rennes University Hospital

Locations

CHU Pontchaillou

Rennes, , France

Countries

France

Other Identifiers

ANSM 2012-A01392-41

Identifier Type: -

Identifier Source: org_study_id