Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis

Hemochromatosis Type 1 Clinical Trial

— SAIFER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01810965
• Other study ID #: ANSM 2012-A01392-41
• Status: Completed
• Phase: N/A
• Start date: June 3, 2013
• Est. completion date: April 19, 2019

Study information

• Verified date: June 2021
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 19, 2019
• Est. primary completion date: April 19, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemochromatosis
• Hemochromatosis Type 1

Intervention

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

Locations

Country	Name	City	State
France	CHU Pontchaillou	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

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