Clinical trial NCT01810965: Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis
Official title: Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis: Pathophysiological and Clinical Implications. Pilot Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hemochromatosis Type 1
Keywords: Hemochromatosis type 1
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2013-03-14
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting
timeFrame: Day 5
Secondary outcomes:
measure: Kinetic of NTBI plasmatic concentration during the 5 days following a bloodletting
timeFrame: Day 5
measure: Maximal variation (delta maximum) of LPI during the 5 days following a bloodletting
timeFrame: Day 5
measure: Maximal variation (delta maximum) of hepcidin during the 5 days following a bloodletting
timeFrame: Day 5
measure: Kinetic of LPI plasmatic concentration during the 5 days following a bloodletting
timeFrame: Day 5
measure: Kinetic of hepcidin plasmatic concentration during the 5 days following a bloodletting
timeFrame: Day 5
measure: CRP
timeFrame: Day 9, day 10, day 11 and day 12
measure: Hemoglobin
timeFrame: Day 9, day 10, day 11 and day 12
measure: Soluble transferrin receptor
timeFrame: Day 9, day 10, day 11 and day 12
measure: EPO
timeFrame: Day 9, day 10, day 11 and day 12
measure: Circadian kinetic of NTBI plasmatic concentration when no bloodletting is performed
timeFrame: Day 1
measure: Circadian kinetic of API plasmatic concentration when no bloodletting is performed
timeFrame: Day 1
measure: Circadian kinetic of hepcidine plasmatic concentration when no bloodletting is performed
timeFrame: Day 1
measure: Maximal variation (delta maximum) of transferrin saturation during the 5 days following a bloodletting
timeFrame: Day 5
measure: Kinetic of transferrin saturation during the 5 days following a bloodletting
timeFrame: Day 5
Other outcomes:
Locations:
city: Rennes
country: France
facility: CHU Pontchaillou
Study officials:
affiliation: Rennes University Hospital
name: Martine Ropert-Bouchet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Bruno Laviolle, MD, PhD
role: STUDY_CHAIR
References: