Analysis of the Modulation of Serum Hepcidin Level in Response to Iron Oral Intake: Potential Interest for the Differential Diagnosis Between Ferroportin Disease and Dysmetabolic Hepatosiderosis.

NCT01949467 | Completed Phase 2

• 1 other identifier: FERHEP
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 4

Brief Summary

The diagnosis of iron overload is a common problem. It is important to optimize the diagnosis to ensure support for patients and their relatives especially regarding genetic disease. Iron overload revealed by a high level of serum ferritin and confirmed by the presence of an excessive amount of iron in the liver is a frequent situation. In a lot of case there is no increase in serum iron and transferrin saturation. This situation may arise in particular in patients with:

• a genetic iron overload related to mutation in the ferroportine gene, leading to a ferroportin disease. The diagnosis is based on the sequencing of the gene,
• a dysmetabolic hepatosiderosis, the most frequent situation , where iron overload is associated with abnormalities in the metabolism of carbohydrates and fats, whereas no genetic cause is identified. However, patients often have similar biological signs and despite the implementation of strict algorithm regarding the diagnostic procedure, it appears that a large number of patients are tested for the mutation in the ferroportin gene, and that mutation is not found in most cases. It is therefore essential to optimize the diagnosis process by introducing additional criteria. The investigators' hypothesis, based on the known elements, is that the response to a single dose of iron will modulate differently the iron parameters measured in serum, including hepcidin level which controls iron metabolism and metals associated with iron. This could be helpful for diagnosis procedure in patients with ferroportin disease or dysmetabolic hepatosiderosis.

Conditions

Hemochromatosis, Type 4; Ferroportin Disease; Dysmetabolic Hepatosiderosis; Diagnosis

Keywords

ferroportin disease; dysmetabolic hepatosiderosis; genetic hemochromatosis; hyperferritinemia; hepcidin; iron fumarate; physiopathological study; diagnosis; HFE gene; TRF2 gene; iron parameters; divalent cations

Outcome Measures

Primary Outcomes (1)

• hepcidemia rate

  The primary endpoint is the maximum variation, of hepcidemia rate (Δmax) after iron oral intake. This variation will be compared between the different groups of included subjects

  Day 1

Secondary Outcomes (2)

• ratios between serum hepcidin level and iron parameters

  Day 1

• serum level of other divalent cations

  day 1

Study Arms (5)

TDHS

OTHER

20 Patients with Treated Dysmetabolic Hepatosiderosis (TDHS)

Drug: iron fumarate

UDHS

OTHER

20 patients with untreated Dysmetabolic Hepatosiderosis (UDHS)

Drug: iron fumarate

TFPD

OTHER

20 patients with treated Ferroportin Disease (TFPD)

Drug: iron fumarate

UFPD

OTHER

20 patients with untreated Ferroportin Disease (UFPD)

Drug: iron fumarate

HV

OTHER

20 Healthy volunteers (HV) patients

Drug: iron fumarate

Interventions

iron fumarate DRUG

All patients will receive a tablet of 66mg of iron, in the form of iron fumarate (Fumafer®) with 50 ml water.

HV; TDHS; TFPD; UDHS; UFPD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman older than 18 years
• Subject having a liver iron overload greater than or equal to 100 umol /g dry liver weight, confirmed by MRI (done performed with body antenna and complete deactivation of the surface antenna) and / or by biochemical assay on liver biopsy, and related to dysmetabolic hepatosiderosis or ferroportin disease.
• The ferroportin disease will be retained when patients will present an hyperferritinemia without elevated transferrin saturation and a heterozygote mutation in the gene encoding ferroportin.
• A dysmetabolic hepatosiderosis will be retained following the usual diagnostic investigation including sequencing of the gene for ferroportin (mutation proven negative), if patients do not show any other cause of iron overload and hyperferritinemia is not related to excessive alcohol intake, non-metabolic liver cytolysis (hepatitis C virus, wilson, autoimmune hepatitis, ...), hemolysis, or inflammatory syndrome.
• Status towards the iron-depletive treatment : either no venesection performed (Dysmetabolic HepatoSiderosis and Ferroportin disease groups) or attack iron depletive treatment completed (Treated Dysmetabolic Hepatosiderosis and Treated Ferroportin Disease groups) with ferritin level less than 100 ng / ml, without anemia and with no venesection in the two last months.
• Having given a free and informed consent in writing
• Affiliate to the social security system.

You may not qualify if:

• Alcohol consumption greater than 30g/d
• Chronic inflammatory disease.
• HIV, HCV or HBV Infection.
• Blood donation in the last three months.
• Infection during the previous seven days before testing
• Staying in altitude (\>1500 m) dating less than 2 months
• Night occupation or shift work.
• Pregnancy
• Protected adults (judicial protection, guardianship and trusteeship) and persons deprived of liberty
• Man or woman older than 18 years.
• Body Mass Index between 18 and 25 kg/m².
• Non smoker or quit smoking for more than 6 months
• Examen clinique normal. Normal clinical examination
• Normal ECG.
• Normal values for routine laboratory tests : serum iron, tranferrin saturation, CBC, ferritin, blood cell count C-reactive protein, AST, ALT, GGT, HDL and LDL cholesterol, triglycerides.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (4)

CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

CHU Limoges

Limoges, France

Location

CHU Montpellier

Montpellier, France

Location

CHU Pontchaillou

Rennes, 35000, France

Location

MeSH Terms

Conditions

Hemochromatosis, type 4; Disease; Hemochromatosis; Hyperferritinemia

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Overload; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2013
• First Posted: September 24, 2013
• Study Start: February 10, 2014
• Primary Completion: December 19, 2017
• Study Completion: December 26, 2018
• Last Updated: March 27, 2019

Record last verified: 2018-08

Locations

FR (4)