Clinical Trial: Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 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.

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 hemo
Sponsor: Rennes University Hospital

Current Primary Outcome: Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting [ Time Frame: Day 5 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome:

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


Information By: Rennes University Hospital

Dates:
Date Received: March 12, 2013
Date Started: March 2013
Date Completion: September 2018
Last Updated: September 26, 2016
Last Verified: September 2016