Hemochromatosis Type 1
Conditions
Keywords
Hemochromatosis type 1
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.
Interventions
PROCEDUREFirst evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)
Sponsors
Rennes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting | Day 5 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Kinetic of NTBI plasmatic concentration during the 5 days following a bloodletting | Day 5 |
| 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 |
| Soluble transferrin receptor | Day 9, day 10, day 11 and day 12 |
Countries
France
Outcome results
None listed