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

This study is currently recruiting participants.
Verified December 2013 by Rennes University Hospital
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01810965
First received: March 12, 2013
Last updated: December 24, 2013
Last verified: December 2013
  Purpose

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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis: Pathophysiological and Clinical Implications. Pilot Study.

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting [ Time Frame: Day 5 ] [ Designated as safety issue: No ]

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

Estimated Enrollment: 14
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 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 hemochromatosic 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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men
  • Aged between 18 and 65
  • 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
  • Active tabagism or tabagism stopped from less than 6 months
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01810965

Contacts
Contact: Martine Ropert-Bouchet, MD 02.99.28.42.75 martine.ropert@chu-rennes.fr

Locations
France
CHU Pontchaillou Recruiting
Rennes, France, 35000
Contact: Martine Ropert-Bouchet, MD    (0) 2.99.28.42.75 ext + 33    martine.ropert@chu-rennes.fr   
Principal Investigator: Martine Ropert-Bouchet, MD         
Sponsors and Collaborators
Rennes University Hospital
Investigators
Principal Investigator: Martine Ropert-Bouchet, MD CHU de Rennes
Study Chair: Bruno Laviolle, MD, PhD CHU de Rennes
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01810965     History of Changes
Other Study ID Numbers: ANSM 2012-A01392-41
Study First Received: March 12, 2013
Last Updated: December 24, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Rennes University Hospital:
Hemochromatosis type 1

Additional relevant MeSH terms:
Hemochromatosis
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on April 17, 2014