HEPFER-Evaluation of a New Phenotypic Biological Marker in Genetic Type 1 Hemochromatosis (HEPFER)

HFE(High iron FE)-related hereditary hemochromatosis has a highly variable penetrance. No phenotypic or genetic markers can predict the disease. The Iron Reabsorption Index (IRI), recently described by our group, correspond to the daily reabsorbed iron for a subject whose iron stock is stable and less than 50 µg / L.

The IRI is constant over time, reflecting the importance of the underlying functional deficit.

Hepcidin / ferritin (H / F) ratio may be an independent and constant over time marker of disease stage.No data are available on the validated values of this ratio.

The goal of this project is to determine the intra-individual variations of the H / F ratio over time during maintenance therapy and to assess the correlation with the IRI.

Study Overview

• Status: Completed
• Conditions: Hereditary Hemochromatosis C282Y Homozygous

Detailed Description

HFE-related hereditary hemochromatosis has a highly variable penetrance : 1% of homozygous women and 30% of homozygous men would develop a clinically expressed disease. No predictive phenotypic or genetic markers are available.

The Iron Reabsorption Index (IRI), recently described by our group, correspond to the daily amount of reabsorbed iron for a subject whose iron stock is less than 50 µg / L and stabilized with maintenance phlebotomy.

For one patient, the IRI is constant over time, probably related to the functional deficit underlying. Unfortunately, IRI is a retrospective marker requiring at least one year of treatment, which limits its practical interest and directs its use for research activity.

We're looking for a more simple phenotypic marker readily available in clinical practice, which would predict at the time of diagnosis the evolution of the disease and therefore would better define the therapeutic options.

The pathophysiology of hemochromatosis is a dysregulation of hepcidin synthesis. We assume that hepcidin / ferritin ratio could be a phenotypic marker like the IRI, stage disease independent and constant over time. Indeed H/F ratio may reflect the adaptability of hepcidin production regulation for a level of iron stock No data are available on the validated values of this ratio. The aim of the project is to determine the intra-individual variations of the H / F ratio over time during maintenance therapy and to assess the correlation with the IRI.

The study involve 30 C282Y homozygous men, followed in a reference center with phlebotomy maintenance therapy and stabilized at a low level of ferritin (<50 µg / L) for at least 1 year.

The intra-individual variation of H/F ration will be determine by 5 samples every 14 days for 8 weeks. The correlation with IRI will be validated externally by the iron load observed at diagnosis. We will take into account other known variation factors like liver damages associated with hemochromatosis at diagnosis.

• Study Type: Observational
• Enrollment (Actual): 31

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35000
    • CHU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

• Men, at least 18 years old
• hereditary hemochrmatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes
• Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L,

Description

Inclusion Criteria:

• Men, at least 18 years old
• hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes
• Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L,
• Written, free and informed consent

Exclusion Criteria:

• Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction.
• Person with a measure of legal protection (guardianship)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
HEPFER cohort; male, aged 18 and over, hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
distribution of values of Hepcidin / ferritin plasma ratio	values of Hepcidin / ferritin plasma ratio	First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between Hepcidin / ferritin plasma ratio and IRI.	First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time
Correlation between Hepcidin / Ferritin ratio before and after treatment	First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time
Distribution of inter-individual Hepcidin / Ferritin ratio according to the stage of liver fibrosis	First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Caroline Jezequel, MD, CHU Rennes Pontchaillou

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 22, 2013
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (Estimate): February 6, 2013

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: hereditary hemochromatosis C282Y homozygous; Iron Reabsorption Index (IRI); Hepcidin / ferritin (H / F) ratio
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Iron Metabolism Disorders; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Iron Overload; Hemochromatosis; Hemosiderosis
• Other Study ID Numbers: 2012-A01170-43

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No