Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis (SAIFER)

Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis: Pathophysiological and Clinical Implications. Pilot Study.

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.

Study Overview

• Status: Completed
• Conditions: Hemochromatosis Type 1
• Intervention / Treatment: Procedure: First evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35000
    • CHU Pontchaillou

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort	Procedure: First evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting	Day 5

Secondary Outcome Measures

Outcome Measure	Time Frame
Kinetic of NTBI plasmatic concentration during the 5 days following a bloodletting	Day 5
Maximal variation (delta maximum) of LPI during the 5 days following a bloodletting	Day 5
Maximal variation (delta maximum) of hepcidin during the 5 days following a bloodletting	Day 5
Kinetic of LPI plasmatic concentration during the 5 days following a bloodletting	Day 5
Kinetic of hepcidin plasmatic concentration during the 5 days following a bloodletting	Day 5
CRP	Day 9, day 10, day 11 and day 12
Hemoglobin	Day 9, day 10, day 11 and day 12
Soluble transferrin receptor	Day 9, day 10, day 11 and day 12
EPO	Day 9, day 10, day 11 and day 12
Circadian kinetic of NTBI plasmatic concentration when no bloodletting is performed	Day 1
Circadian kinetic of API plasmatic concentration when no bloodletting is performed	Day 1
Circadian kinetic of hepcidine plasmatic concentration when no bloodletting is performed	Day 1
Maximal variation (delta maximum) of transferrin saturation during the 5 days following a bloodletting	Day 5
Kinetic of transferrin saturation during the 5 days following a bloodletting	Day 5

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Martine Ropert-Bouchet, MD, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 3, 2013
• Primary Completion (ACTUAL): April 19, 2019
• Study Completion (ACTUAL): April 19, 2019

Study Registration Dates

• First Submitted: March 12, 2013
• First Submitted That Met QC Criteria: March 12, 2013
• First Posted (ESTIMATE): March 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Hemochromatosis type 1
• 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: ANSM 2012-A01392-41